Journal articles: 'Glial scar formation'

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Perez-Gianmarco, Lucila, and Maria Kukley. "Understanding the Role of the Glial Scar through the Depletion of Glial Cells after Spinal Cord Injury." Cells 12, no. 14 (July 13, 2023): 1842. http://dx.doi.org/10.3390/cells12141842.

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Spinal cord injury (SCI) is a condition that affects between 8.8 and 246 people in a million and, unlike many other neurological disorders, it affects mostly young people, causing deficits in sensory, motor, and autonomic functions. Promoting the regrowth of axons is one of the most important goals for the neurological recovery of patients after SCI, but it is also one of the most challenging goals. A key event after SCI is the formation of a glial scar around the lesion core, mainly comprised of astrocytes, NG2+-glia, and microglia. Traditionally, the glial scar has been regarded as detrimental to recovery because it may act as a physical barrier to axon regrowth and release various inhibitory factors. However, more and more evidence now suggests that the glial scar is beneficial for the surrounding spared tissue after SCI. Here, we review experimental studies that used genetic and pharmacological approaches to ablate specific populations of glial cells in rodent models of SCI in order to understand their functional role. The studies showed that ablation of either astrocytes, NG2+-glia, or microglia might result in disorganization of the glial scar, increased inflammation, extended tissue degeneration, and impaired recovery after SCI. Hence, glial cells and glial scars appear as important beneficial players after SCI.

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Nicaise, Alexandra M., Andrea D’Angelo, Rosana-Bristena Ionescu, Grzegorz Krzak, Cory M. Willis, and Stefano Pluchino. "The role of neural stem cells in regulating glial scar formation and repair." Cell and Tissue Research 387, no. 3 (November 25, 2021): 399–414. http://dx.doi.org/10.1007/s00441-021-03554-0.

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AbstractGlial scars are a common pathological occurrence in a variety of central nervous system (CNS) diseases and injuries. They are caused after severe damage and consist of reactive glia that form a barrier around the damaged tissue that leads to a non-permissive microenvironment which prevents proper endogenous regeneration. While there are a number of therapies that are able to address some components of disease, there are none that provide regenerative properties. Within the past decade, neural stem cells (NSCs) have been heavily studied due to their potent anti-inflammatory and reparative capabilities in disease and injury. Exogenously applied NSCs have been found to aid in glial scar healing by reducing inflammation and providing cell replacement. However, endogenous NSCs have also been found to contribute to the reactive environment by different means. Further understanding how NSCs can be leveraged to aid in the resolution of the glial scar is imperative in the use of these cells as regenerative therapies. To do so, humanised 3D model systems have been developed to study the development and maintenance of the glial scar. Herein, we explore the current work on endogenous and exogenous NSCs in the glial scar as well as the novel 3D stem cell–based technologies being used to model this pathology in a dish.

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Bao, Yi, Luye Qin, Eunhee Kim, Sangram Bhosle, Hengchang Guo, Maria Febbraio, Renee E. Haskew-Layton, Rajiv Ratan, and Sunghee Cho. "CD36 is Involved in Astrocyte Activation and Astroglial Scar Formation." Journal of Cerebral Blood Flow & Metabolism 32, no. 8 (April 18, 2012): 1567–77. http://dx.doi.org/10.1038/jcbfm.2012.52.

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Inflammation is an essential component for glial scar formation. However, the upstream mediator(s) that triggers the process has not been identified. Previously, we showed that the expression of CD36, an inflammatory mediator, occurs in a subset of astcotyes in the peri-infarct area where the glial scar forms. This study investigates a role for CD36 in astrocyte activation and glial scar formation in stroke. We observed that the expression of CD36 and glial fibrillary acidic protein (GFAP) coincided in control and injured astrocytes and in the brain. Furthermore, GFAP expression was attenuated in CD36 small interfering RNA transfected astrocytes or in the brain of CD36 knockout (KO) mice, suggesting its involvement in GFAP expression. Using an in-vitro model of wound healing, we found that CD36 deficiency attenuated the proliferation of astrocytes and delayed closure of the wound gap. Furthermore, stroke-induced GFAP expression and scar formation were significantly attenuated in the CD36 KO mice compared with wild type. These findings identify CD36 as a novel mediator for injury-induced astrogliosis and scar formation. Targeting CD36 may serve as a potential strategy to reduce glial scar formation in stroke.

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ZHANG, H., K. UCHIMURA, and K. KADOMATSU. "Brain Keratan Sulfate and Glial Scar Formation." Annals of the New York Academy of Sciences 1086, no. 1 (November 1, 2006): 81–90. http://dx.doi.org/10.1196/annals.1377.014.

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Renault-Mihara, Francois, Masahiko Mukaino, Munehisa Shinozaki, Hiromi Kumamaru, Satoshi Kawase, Matthieu Baudoux, Toshiki Ishibashi, et al. "Regulation of RhoA by STAT3 coordinates glial scar formation." Journal of Cell Biology 216, no. 8 (June 22, 2017): 2533–50. http://dx.doi.org/10.1083/jcb.201610102.

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Understanding how the transcription factor signal transducer and activator of transcription–3 (STAT3) controls glial scar formation may have important clinical implications. We show that astrocytic STAT3 is associated with greater amounts of secreted MMP2, a crucial protease in scar formation. Moreover, we report that STAT3 inhibits the small GTPase RhoA and thereby controls actomyosin tonus, adhesion turnover, and migration of reactive astrocytes, as well as corralling of leukocytes in vitro. The inhibition of RhoA by STAT3 involves ezrin, the phosphorylation of which is reduced in STAT3-CKO astrocytes. Reduction of phosphatase and tensin homologue (PTEN) levels in STAT3-CKO rescues reactive astrocytes dynamics in vitro. By specific targeting of lesion-proximal, reactive astrocytes in Nestin-Cre mice, we show that reduction of PTEN rescues glial scar formation in Nestin-Stat3+/− mice. These findings reveal novel intracellular signaling mechanisms underlying the contribution of reactive astrocyte dynamics to glial scar formation.

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Goussev, Staci, Jung-Yu C. Hsu, Yong Lin, Tjoson Tjoa, Nino Maida, Zena Werb, and Linda J. Noble-Haeusslein. "Differential temporal expression of matrix metalloproteinases after spinal cord injury: relationship to revascularization and wound healing." Journal of Neurosurgery: Spine 99, no. 2 (September 2003): 188–97. http://dx.doi.org/10.3171/spi.2003.99.2.0188.

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Object. Matrix metalloproteinases (MMPs), particularly MMP-9/gelatinase B, promote early inflammation and barrier disruption after spinal cord injury (SCI). Early blockade of MMPs after injury provides neuroprotection and improves motor outcome. There is recent evidence, however, that MMP-9 and MMP-2/gelatinase A participate in later wound healing in the injured cord. The authors therefore examined the activity of these gelatinases during revascularization and glial scar formation in the contused murine spinal cord. Methods. Gelatinase activity was evaluated using gelatin zymography 24 hours after a mild, moderate, or severe contusion injury. The active form of MMP-2 was not detected, whereas MMP-9 activity was evident in all SCI groups and rose with increasing injury severity. The temporal expression of gelatinases was then examined using gelatin zymography after a moderate SCI. The active form of MMP-9 was most prominent at 1 day, extended through the early period of revascularization, and returned to control by 14 days. The active form of MMP-2 appeared at 7 days postinjury and remained elevated compared with that documented in sham-treated mice for at least 21 days. Increased MMP-2 activity coincided with both revascularization and glial scar formation. Using in situ zymography, gelatinolytic activity was detected in the meninges, vascular elements, glia, and macrophage-like cells in the injured cord. Results of immunolabeling confirmed the presence of gelatinase in vessels during revascularization and in reactive astrocytes associated with glial scar formation. Conclusions. These findings suggest that although MMP-9 and -2 exhibit overlapping expression during revascularization, the former is associated with acute injury responses and the latter with formation of a glial scar.

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Hu, Rong, Jianjun Zhou, Chunxia Luo, Jiangkai Lin, Xianrong Wang, Xiaoguang Li, Xiuwu Bian, et al. "Glial scar and neuroregeneration: histological, functional, and magnetic resonance imaging analysis in chronic spinal cord injury." Journal of Neurosurgery: Spine 13, no. 2 (August 2010): 169–80. http://dx.doi.org/10.3171/2010.3.spine09190.

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Object A glial scar is thought to be responsible for halting neuroregeneration following spinal cord injury (SCI). However, little quantitative evidence has been provided to show the relationship of a glial scar and axonal regrowth after injury. Methods In this study performed in rats and dogs, a traumatic SCI model was made using a weight-drop injury device, and tissue sections were stained with H & E for immunohistochemical analysis. The function and behavior of model animals were tested using electrophysiological recording and the Basso-Beattie-Bresnahan Locomotor Rating Scale, respectively. The cavity in the spinal cord after SCI in dogs was observed using MR imaging. Results The morphological results showed that the formation of an astroglial scar was defined at 4 weeks after SCI. While regenerative axons reached the vicinity of the lesion site, the glial scar blocked the extension of regrown axons. In agreement with these findings, the electrophysiological, behavioral, and in vivo MR imaging tests showed that functional recovery reached a plateau at 4 weeks after SCI. The thickness of the glial scars in the injured rat spinal cords was also measured. The mean thickness of the glial scar rostral and caudal to the lesion cavity was 107.00 ± 20.12 μm; laterally it was 69.92 ± 15.12 μm. Conclusions These results provide comprehensive evidence indicating that the formation of a glial scar inhibits axonal regeneration at 4 weeks after SCI. This study reveals a critical time window of postinjury recovery and a detailed spatial orientation of glial scar, which would provide an important basis for the development of therapeutic strategy for glial scar ablation.

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Conrad, Sabine, Hermann J. Schluesener, Mehdi Adibzahdeh, and Jan M. Schwab. "Spinal cord injury induction of lesional expression of profibrotic and angiogenic connective tissue growth factor confined to reactive astrocytes, invading fibroblasts and endothelial cells." Journal of Neurosurgery: Spine 2, no. 3 (March 2005): 319–26. http://dx.doi.org/10.3171/spi.2005.2.3.0319.

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Object. The glial scar composed of astrogliosis and extracellular matrix deposition represents a major impediment to axonal regeneration. The authors investigated the role of a novel profibrotic and angiogenic peptide connective tissue growth factor (CTGF [Hcs24/IGFBP-r2P]) in glial scar formation following spinal cord injury (SCI) in rats. Methods. The effects of SCI on CTGF expression during glial scar maturation 1 day to 1 month post-SCI were investigated using fluorescein-activated cell sorter (FACS) immunohistochemical analysis; these findings were compared with those obtained in sham-operated (control) spinal cords. The CTGF-positive cells accumulated at the spinal cord lesion site (p < 0.0001) corresponding to areas of glial scar formation. In the perilesional rim, CTGF expression was confined to invading vimentin-positive, glial fibrillary acidic protein (GFAP)—negative fibroblastoid cells, endothelial and smooth-muscle cells of laminin-positive vessels, and GFAP-positive reactive astrocytes. The CTGF-positive astrocytes coexpressed the activation-associated intermediate filaments nestin, vimentin (> 80%), and mesenchymal scar component fibronectin (50%). Conclusions. The restricted accumulation of CTGF-reactive astrocytes and CTGF-positive fibroblastoid cells lining the laminin-positive basal neolamina suggests participation of these cells in scar formation. In addition, perilesional upregulation of endothelial and smooth-muscle CTGF expression points to a role in blood—brain barrier function modulating edema-induced secondary damage.

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Chen, Xuning, and Weiping Zhu. "A Mathematical Model of Regenerative Axon Growing along Glial Scar after Spinal Cord Injury." Computational and Mathematical Methods in Medicine 2016 (2016): 1–9. http://dx.doi.org/10.1155/2016/3030454.

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A major factor in the failure of central nervous system (CNS) axon regeneration is the formation of glial scar after the injury of CNS. Glial scar generates a dense barrier which the regenerative axons cannot easily pass through or by. In this paper, a mathematical model was established to explore how the regenerative axons grow along the surface of glial scar or bypass the glial scar. This mathematical model was constructed based on the spinal cord injury (SCI) repair experiments by transplanting Schwann cells as bridge over the glial scar. The Lattice Boltzmann Method (LBM) was used in this model for three-dimensional numerical simulation. The advantage of this model is that it provides a parallel and easily implemented algorithm and has the capability of handling complicated boundaries. Using the simulated data, two significant conclusions were made in this study:(1)the levels of inhibitory factors on the surface of the glial scar are the main factors affecting axon elongation and(2)when the inhibitory factor levels on the surface of the glial scar remain constant, the longitudinal size of the glial scar has greater influence on the average rate of axon growth than the transverse size. These results will provide theoretical guidance and reference for researchers to design efficient experiments.

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Graboviy, O. M., T. S. Mervinsky, S. I. Savosko, and L. M. Yaremenko. "Dynamics of changes in the representation of mesenchymal cells in the forming glial scar during dexamethasone application." Reports of Morphology 30, no. 3 (September 19, 2024): 25–32. http://dx.doi.org/10.31393/morphology-journal-2024-30(3)-03.

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Mesenchymal stem cells are involved in cellular responses in the injured brain after a stroke. The formation of a glial scar is a local response in the brain to damage, and mesenchymal stem cells may be involved in the processes of scar formation. Mesenchymal stem cells express a range of membrane markers, the expression profile of which obviously changes as they differentiate and depends on the microenvironment in which these cells are located. However, it is still unclear where the stem cells in the damaged brain originate from – whether they come from a resident source or from the bone marrow, although an increase in CD34+ cells in the blood of stroke patients is a well-known fact. In this study, we consider the hypothesis regarding the appearance of mesenchymal stem cells in the brain during a stroke and their potential involvement in the formation of a glial scar. The aim of the study is to investigate the involvement of CD44+, CD68+, CD90+, and CD146+ cells in the formation of a glial scar during hemorrhagic stroke and the changes in their representation under the effect of dexamethasone. To achieve this goal, we simulated hemorrhagic stroke in rats and compared the results of immunohistochemical detection of CD44+, CD68+, CD90+, and CD146+ cells in the area of glial scar formation against the dexamethasone administration. We obtained convincing results of differences in the activity and timing of migration of cells expressing CD44 compared to cells expressing CD68, CD90, and CD146. There is a tendency indicating a dependence between the detection of CD44+ cells and the extent of the damage, while the detection of CD68+, CD90+, and CD146+ cells is strongly correlated and increases under the effect of dexamethasone. Cells expressing CD44 were the main participants in the infiltrating pool of cells in the acute phase, but dexamethasone delayed the peak accumulation of CD44+ cells in the forming scar. There were some changes in the detection of these cells around the hemorrhage during dexamethasone treatment, which may indicate its modulating effect on mesenchymal stem cells during glial scar formation. The more frequent detection of CD68+, CD90+, and CD146+ cells can be considered a manifestation of the potential modification by dexamethasone of cellular reactions involved in glial scar formation in the brain after a stroke. The study of the roles of specific immunophenotypes of mesenchymal stem cells in the areas of glial scar formation following hemorrhagic stroke opens new perspectives in the study of brain recovery processes.

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Chung, Joonho, Moon Hang Kim, Yong Je Yoon, Kil Hwan Kim, So Ra Park, and Byung Hyune Choi. "Effects of granulocyte colony–stimulating factor and granulocyte-macrophage colony–stimulating factor on glial scar formation after spinal cord injury in rats." Journal of Neurosurgery: Spine 21, no. 6 (December 2014): 966–73. http://dx.doi.org/10.3171/2014.8.spine131090.

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Object This study investigated the effects of granulocyte colony–stimulating factor (G-CSF) on glial scar formation after spinal cord injury (SCI) in rats and compared the therapeutic effects between G-CSF and granulocytemacrophage colony–stimulating factor (GM-CSF) to evaluate G-CSF as a potential substitute for GM-CSF in clinical application. Methods Rats were randomly assigned to 1 of 4 groups: a sham-operated group (Group 1), an SCI group without treatment (Group 2), an SCI group treated with G-CSF (Group 3), and an SCI group treated with GM-CSF (Group 4). G-CSF and GM-CSF were administered via intraperitoneal injection immediately after SCI. The effects of G-CSF and GM-CSF on functional recovery, glial scar formation, and axonal regeneration were evaluated and compared. Results The rats in Groups 3 and 4 showed better functional recovery and more decreased cavity sizes than those in Group 2 (p < 0.05). Both G-CSF and GM-CSF suppressed intensive expression of glial fibrillary acidic protein around the cavity at 4 weeks and reduced the expression of chondroitin sulfate proteoglycans (p < 0.05). Also, early administration of G-CSF and GM-CSF protected axon fibers from destructive injury and facilitated axonal regeneration. There were no significant differences in comparisons of functional recovery, glial scar formation, and axonal regeneration between G-CSF and GM-CSF. Conclusions G-CSF suppressed glial scar formation after SCI in rats, possibly by restricting the expression of glial fibrillary acidic protein and chondroitin sulfate proteoglycans, which might facilitate functional recovery from SCI. GM-CSF and G-CSF had similar effects on glial scar formation and functional recovery after SCI, suggesting that G-CSF can potentially be substituted for GM-CSF in the treatment of SCI.

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Onodera, Junya, Yuji Ikegaya, and Ryuta Koyama. "Involvement of microglial TRPV4 on glial scar formation." Proceedings for Annual Meeting of The Japanese Pharmacological Society 95 (2022): 1—P—020. http://dx.doi.org/10.1254/jpssuppl.95.0_1-p-020.

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Sutin, Jerome, and Ronald Griffith. "β-Adrenergic Receptor Blockade Suppresses Glial Scar Formation." Experimental Neurology 120, no. 2 (April 1993): 214–22. http://dx.doi.org/10.1006/exnr.1993.1056.

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Rooney, Gemma E., Toshiki Endo, Syed Ameenuddin, Bingkun Chen, Sandeep Vaishya, LouAnn Gross, Terry K. Schiefer, et al. "Importance of the vasculature in cyst formation after spinal cord injury." Journal of Neurosurgery: Spine 11, no. 4 (October 2009): 432–37. http://dx.doi.org/10.3171/2009.4.spine08784.

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Object Glial scar and cystic formation greatly contribute to the inhibition of axonal regeneration after spinal cord injury (SCI). Attempts to promote axonal regeneration are extremely challenging in this type of hostile environment. The objective of this study was to examine the surgical methods that may be used to assess the factors that influence the level of scar and cystic formation in SCI. Methods In the first part of this study, a complete transection was performed at vertebral level T9–10 in adult female Sprague-Dawley rats. The dura mater was either left open (control group) or was closed using sutures or hyaluronic acid. In the second part of the study, complete or subpial transection was performed, with the same dural closure technique applied to both groups. Histological analysis of longitudinal sections of the spinal cord was performed, and the percentage of scar and cyst formation was determined. Results Dural closure using sutures resulted in significantly less glial scar formation (p = 0.0248), while incorporation of the subpial transection surgical technique was then shown to significantly decrease cyst formation (p < 0.0001). Conclusions In this study, the authors demonstrated the importance of the vasculature in cyst formation after spinal cord trauma and confirmed the importance of dural closure in reducing glial scar formation.

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Clifford, Tanner, Zachary Finkel, Brianna Rodriguez, Adelina Joseph, and Li Cai. "Current Advancements in Spinal Cord Injury Research—Glial Scar Formation and Neural Regeneration." Cells 12, no. 6 (March 9, 2023): 853. http://dx.doi.org/10.3390/cells12060853.

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Spinal cord injury (SCI) is a complex tissue injury resulting in permanent and degenerating damage to the central nervous system (CNS). Detrimental cellular processes occur after SCI, including axonal degeneration, neuronal loss, neuroinflammation, reactive gliosis, and scar formation. The glial scar border forms to segregate the neural lesion and isolate spreading inflammation, reactive oxygen species, and excitotoxicity at the injury epicenter to preserve surrounding healthy tissue. The scar border is a physicochemical barrier composed of elongated astrocytes, fibroblasts, and microglia secreting chondroitin sulfate proteoglycans, collogen, and the dense extra-cellular matrix. While this physiological response preserves viable neural tissue, it is also detrimental to regeneration. To overcome negative outcomes associated with scar formation, therapeutic strategies have been developed: the prevention of scar formation, the resolution of the developed scar, cell transplantation into the lesion, and endogenous cell reprogramming. This review focuses on cellular/molecular aspects of glial scar formation, and discusses advantages and disadvantages of strategies to promote regeneration after SCI.

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Liu, Jingzhou, Xin Xin, Jiejie Sun, Yueyue Fan, Xun Zhou, Wei Gong, Meiyan Yang, et al. "Dual-targeting AAV9P1-mediated neuronal reprogramming in a mouse model of traumatic brain injury." Neural Regeneration Research 19, no. 3 (July 20, 2023): 629–35. http://dx.doi.org/10.4103/1673-5374.380907.

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Abstract JOURNAL/nrgr/04.03/01300535-202403000-00038/inline-graphic1/v/2023-08-11T153926Z/r/image-tiff Traumatic brain injury results in neuronal loss and glial scar formation. Replenishing neurons and eliminating the consequences of glial scar formation are essential for treating traumatic brain injury. Neuronal reprogramming is a promising strategy to convert glial scars to neural tissue. However, previous studies have reported inconsistent results. In this study, an AAV9P1 vector incorporating an astrocyte-targeting P1 peptide and glial fibrillary acidic protein promoter was used to achieve dual-targeting of astrocytes and the glial scar while minimizing off-target effects. The results demonstrate that AAV9P1 provides high selectivity of astrocytes and reactive astrocytes. Moreover, neuronal reprogramming was induced by downregulating the polypyrimidine tract-binding protein 1 gene via systemic administration of AAV9P1 in a mouse model of traumatic brain injury. In summary, this approach provides an improved gene delivery vehicle to study neuronal programming and evidence of its applications for traumatic brain injury.

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Sofroniew, Michael V. "Molecular dissection of reactive astrogliosis and glial scar formation." Trends in Neurosciences 32, no. 12 (December 2009): 638–47. http://dx.doi.org/10.1016/j.tins.2009.08.002.

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Wang, Haijun, Guobin Song, Haoyu Chuang, Chengdi Chiu, Ahmed Abdelmaksoud, Youfan Ye, and Lei Zhao. "Portrait of glial scar in neurological diseases." International Journal of Immunopathology and Pharmacology 31 (January 2018): 205873841880140. http://dx.doi.org/10.1177/2058738418801406.

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Fibrosis is formed after injury in most of the organs as a common and complex response that profoundly affects regeneration of damaged tissue. In central nervous system (CNS), glial scar grows as a major physical and chemical barrier against regeneration of neurons as it forms dense isolation and creates an inhibitory environment, resulting in limitation of optimal neural function and permanent deficits of human body. In neurological damages, glial scar is mainly attributed to the activation of resident astrocytes which surrounds the lesion core and walls off intact neurons. Glial cells induce the infiltration of immune cells, resulting in transient increase in extracellular matrix deposition and inflammatory factors which inhibit axonal regeneration, impede functional recovery, and may contribute to the occurrence of neurological complications. However, recent studies have underscored the importance of glial scar in neural protection and functional improvement depending on the specific insults which involves various pivotal molecules and signaling. Thus, to uncover the veil of scar formation in CNS may provide rewarding therapeutic targets to CNS diseases such as chronic neuroinflammation, brain stroke, spinal cord injury (SCI), traumatic brain injury (TBI), brain tumor, and epileptogenesis. In this article, we try to describe the new portrait of glial scar and trending of research in neurological diseases to readers.

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Korte, G. E., M. Marko, and G. Hageman. "High-voltage electron microscopy of subretinal scar formation." Proceedings, annual meeting, Electron Microscopy Society of America 50, no. 1 (August 1992): 486–87. http://dx.doi.org/10.1017/s0424820100122836.

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Sodium iodate iv. damages the retinal pigment epithelium (RPE) in rabbits. Where RPE does not regenerate (e.g., 1,2) Muller glial cells (MC) forma subretinal scar that replaces RPE. The MC response was studied by HVEM in 3D computer reconstructions of serial thick sections, made using the STEREC0N program (3), and the HVEM at the NYS Dept. of Health in Albany, NY. Tissue was processed for HVEM or immunofluorescence localization of a monoclonal antibody recognizing MG microvilli (4).

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Rodriguez-Grande, Beatriz, Matimba Swana, Loan Nguyen, Pavlos Englezou, Samaneh Maysami, Stuart M. Allan, Nancy J. Rothwell, Cecilia Garlanda, Adam Denes, and Emmanuel Pinteaux. "The Acute-Phase Protein PTX3 is an Essential Mediator of Glial Scar Formation and Resolution of Brain Edema after Ischemic Injury." Journal of Cerebral Blood Flow & Metabolism 34, no. 3 (December 18, 2013): 480–88. http://dx.doi.org/10.1038/jcbfm.2013.224.

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Acute-phase proteins (APPs) are key effectors of the immune response and are routinely used as biomarkers in cerebrovascular diseases, but their role during brain inflammation remains largely unknown. Elevated circulating levels of the acute-phase protein pentraxin-3 (PTX3) are associated with worse outcome in stroke patients. Here we show that PTX3 is expressed in neurons and glia in response to cerebral ischemia, and that the proinflammatory cytokine interleukin-1 (IL-1) is a key driver of PTX3 expression in the brain after experimental stroke. Gene deletion of PTX3 had no significant effects on acute ischemic brain injury. In contrast, the absence of PTX3 strongly compromised blood–brain barrier integrity and resolution of brain edema during recovery after ischemic injury. Compromised resolution of brain edema in PTX3-deficient mice was associated with impaired glial scar formation and alterations in scar-associated extracellular matrix production. Our results suggest that PTX3 expression induced by proinflammatory signals after ischemic brain injury is a critical effector of edema resolution and glial scar formation. This highlights the potential role for inflammatory molecules in brain recovery after injury and identifies APPs, in particular PTX3, as important targets in ischemic stroke and possibly other brain inflammatory disorders.

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Carvalho, Juliana Casanovas de, César Augusto Abreu-Pereira, Lucas Cauê da Silva Assunção, Rosana Costa Casanovas, Ana Lucia Abreu-Silva, and Matheus Levi Tajra Feitosa. "Correlation of Nogo A release with glia scar formation in spinal cord injury." Research, Society and Development 10, no. 6 (May 29, 2021): e25410615688. http://dx.doi.org/10.33448/rsd-v10i6.15688.

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Several axonal growth inhibitors have already been identified following spinal cord injury, the most known being myelin-derived proteins, such as Nogo-A. The present study aimed to correlate the formation of glial scar with the beginning of growth inhibitor, Nogo-A, release in rats previously submitted to compressive spinal cord injury. For this, 12 male and female Wistar rats (250 ± 50g) were divided into 3 groups of 4 animals each, according to the animals' euthanasia time after spinal cord injury (G3 - three days; G5 - five days; G7 - seven days). Spinal cord injuries were induced by means of dorsal laminectomy of the T10 vertebra and epidural compression. Histopathological evaluation and immunoreactivity of the Nogo-A axonal growth inhibitor were performed. It was observed that there was the release of the axonal inhibitor Nogo-A after 24h after the occurrence of spinal cord injury, and that the glial scar must be maintained, in this time interval, in order to guarantee the rebalancing of the post-trauma environment. Thus, it is suggested that the glial scar should be maintained in the acute phase of the lesion, guaranteeing its numerous benefits for the rebalancing of the post-injured environment and, after 24 hours, when the release of the studied axonal growth inhibitor begins, it should be removed.

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Li, Xin, Yan Qian, Wanling Shen, Shiying Zhang, Hui Han, Yu Zhang, Shuangmei Liu, Shaokun Lv, and Xiuying Zhang. "Mechanism of SET8 Activates the Nrf2-KEAP1-ARE Signaling Pathway to Promote the Recovery of Motor Function after Spinal Cord Injury." Mediators of Inflammation 2023 (March 10, 2023): 1–13. http://dx.doi.org/10.1155/2023/4420592.

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Background. Spinal cord injury (SCI) is a common injury of the central nervous system (CNS), and astrocytes are relatively abundant glial cells in the CNS that impairs the recovery of motor function after SCI. It was confirmed that the oxidative stress of mitochondria leads to the accumulation of reactive oxygen species (ROS) in cells, which plays a key role in the motor function of astrocytes. However, the mechanism by which oxidative stress affects astrocyte motility after SCI is still unexplained. Therefore, this study investigated the influence of SET8-regulated oxidative stress on astrocyte autophagy levels after SCI in rats and the potential mechanisms of action. Methods. We used real-time quantitative PCR, western blotting, and immunohistochemical staining to analyze SET8, Keap1, and Nrf2 expression at the cellular level and in SCI tissues. ChIP to detect H4K20me1 enrichment in the Keap1 promoter region under OE-SET8 (overexpression of SET8) conditions. Western blotting was used to assess the expression of signature proteins of astrocytes, proteins associated with autophagy, proteins associated with glial scar formation, reactive oxygen species (ROS) levels in cells using DHE staining, and astrocyte number, morphological alterations, and induction of glial scar formation processes using immunofluorescence. In addition, the survival rate of neurons after SCI in rats was examined by using NiSSl staining. Results. OE-SET8 upregulates the enrichment of H4K20me1 in Keap1, inhibits Keap1 expression, activates the Nrf2-ARE signaling pathway to suppress ROS accumulation, inhibits oxidative stress-induced autophagy and glial scar formation in astrocytes, and leads to reduced neuronal loss, which promoted the recovery and improvement of motor function after SCI in rats. Conclusion. Overexpression of SET8 alleviated oxidative stress by regulating Keap1/Nrf2/ARE, inhibited astrocyte autophagy levels, and reduced glial scar formation as well as neuronal loss, thereby promoting improved recovery of motor function after SCI. Thus, the SET8/H4K20me1 regulatory function may be a promising cellular therapeutic intervention point after SCI.

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Badan, I., B. Buchhold, A. Hamm, M. Gratz, L. C. Walker, D. Platt, Ch Kessler, and A. Popa-Wagner. "Accelerated Glial Reactivity to Stroke in Aged Rats Correlates with Reduced Functional Recovery." Journal of Cerebral Blood Flow & Metabolism 23, no. 7 (July 2003): 845–54. http://dx.doi.org/10.1097/01.wcb.0000071883.63724.a7.

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Following cerebral ischemia, perilesional astrocytes and activated microglia form a glial scar that hinders the genesis of new axons and blood vessels in the infarcted region. Since glial reactivity is chronically augmented in the normal aging brain, the authors hypothesized that postischemic gliosis would be temporally abnormal in aged rats compared to young rats. Focal cerebral ischemia was produced by reversible occlusion of the right middle cerebral artery in 3- and 20-month-old male Sprague Dawley rats. The functional outcome was assessed in neurobehavioral tests at 3, 7, 14, and 28 days after surgery. Brain tissue was immunostained for microglia, astrocytes, oligodendrocytes, and endothelial cells. Behaviorally, aged rats were more severely impaired by stroke and showed diminished functional recovery compared with young rats. Histologically, a gradual activation of both microglia and astrocytes that peaked by days 14 to 28 with the formation of a glial scar was observed in young rats, whereas aged rats showed an accelerated astrocytic and microglial reaction that peaked during the first week after stroke. Oligodendrocytes were strongly activated at early stages of infarct development in all rats, but this activation persisted in aged rats. Therefore, the development of the glial scar was abnormally accelerated in aged rats and coincided with the stagnation of recovery in these animals. These results suggest that a temporally anomalous gliotic reaction to cerebral ischemia in aged rats leads to the premature formation of scar tissue that impedes functional recovery after stroke.

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Pekny, Milos, Clas B. Johansson, Camilla Eliasson, Josefina Stakeberg, Åsa Wallén, Thomas Perlmann, Urban Lendahl, Christer Betsholtz, Claes-Henric Berthold, and Jonas Frisén. "Abnormal Reaction to Central Nervous System Injury in Mice Lacking Glial Fibrillary Acidic Protein and Vimentin." Journal of Cell Biology 145, no. 3 (May 3, 1999): 503–14. http://dx.doi.org/10.1083/jcb.145.3.503.

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In response to injury of the central nervous system, astrocytes become reactive and express high levels of the intermediate filament (IF) proteins glial fibrillary acidic protein (GFAP), vimentin, and nestin. We have shown that astrocytes in mice deficient for both GFAP and vimentin (GFAP−/−vim−/−) cannot form IFs even when nestin is expressed and are thus devoid of IFs in their reactive state. Here, we have studied the reaction to injury in the central nervous system in GFAP−/−, vimentin−/−, or GFAP−/−vim−/− mice. Glial scar formation appeared normal after spinal cord or brain lesions in GFAP−/− or vimentin−/− mice, but was impaired in GFAP−/−vim−/− mice that developed less dense scars frequently accompanied by bleeding. These results show that GFAP and vimentin are required for proper glial scar formation in the injured central nervous system and that some degree of functional overlap exists between these IF proteins.

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Wiemann, Susanne, Jacqueline Reinhard, and Andreas Faissner. "Immunomodulatory role of the extracellular matrix protein tenascin-C in neuroinflammation." Biochemical Society Transactions 47, no. 6 (December 17, 2019): 1651–60. http://dx.doi.org/10.1042/bst20190081.

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The extracellular matrix (ECM) consists of a dynamic network of various macromolecules that are synthesized and released by surrounding cells into the intercellular space. Glycoproteins, proteoglycans and fibrillar proteins are main components of the ECM. In addition to general functions such as structure and stability, the ECM controls several cellular signaling pathways. In this context, ECM molecules have a profound influence on intracellular signaling as receptor-, adhesion- and adaptor-proteins. Due to its various functions, the ECM is essential in the healthy organism, but also under pathological conditions. ECM constituents are part of the glial scar, which is formed in several neurodegenerative diseases that are accompanied by the activation and infiltration of glia as well as immune cells. Remodeling of the ECM modulates the release of pro- and anti-inflammatory cytokines affecting the fate of immune, glial and neuronal cells. Tenascin-C is an ECM glycoprotein that is expressed during embryonic central nervous system (CNS) development. In adults it is present at lower levels but reappears under pathological conditions such as in brain tumors, following injury and in neurodegenerative disorders and is highly associated with glial reactivity as well as scar formation. As a key modulator of the immune response during neurodegeneration in the CNS, tenascin-C is highlighted in this mini-review.

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Huang, Lijie, Zhe-Bao Wu, Qichuan ZhuGe, WeiMing Zheng, Bei Shao, Brian Wang, Fen Sun, and Kunlin Jin. "Glial Scar Formation Occurs in the Human Brain after Ischemic Stroke." International Journal of Medical Sciences 11, no. 4 (2014): 344–48. http://dx.doi.org/10.7150/ijms.8140.

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Beach, Krista M., Jianbo Wang, and Deborah C. Otteson. "Regulation of Stem Cell Properties of Müller Glia by JAK/STAT and MAPK Signaling in the Mammalian Retina." Stem Cells International 2017 (2017): 1–15. http://dx.doi.org/10.1155/2017/1610691.

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In humans and other mammals, the neural retina does not spontaneously regenerate, and damage to the retina that kills retinal neurons results in permanent blindness. In contrast to embryonic stem cells, induced pluripotent stem cells, and embryonic/fetal retinal stem cells, Müller glia offer an intrinsic cellular source for regenerative strategies in the retina. Müller glia are radial glial cells within the retina that maintain retinal homeostasis, buffer ion flux associated with phototransduction, and form the blood/retinal barrier within the retina proper. In injured or degenerating retinas, Müller glia contribute to gliotic responses and scar formation but also show regenerative capabilities that vary across species. In the mammalian retina, regenerative responses achieved to date remain insufficient for potential clinical applications. Activation of JAK/STAT and MAPK signaling by CNTF, EGF, and FGFs can promote proliferation and modulate the glial/neurogenic switch. However, to achieve clinical relevance, additional intrinsic and extrinsic factors that restrict or promote regenerative responses of Müller glia in the mammalian retina must be identified. This review focuses on Müller glia and Müller glial-derived stem cells in the retina and phylogenetic differences among model vertebrate species and highlights some of the current progress towards understanding the cellular mechanisms regulating their regenerative response.

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Otte, Elisabeth, Andreas Vlachos, and Maria Asplund. "Engineering strategies towards overcoming bleeding and glial scar formation around neural probes." Cell and Tissue Research 387, no. 3 (January 14, 2022): 461–77. http://dx.doi.org/10.1007/s00441-021-03567-9.

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AbstractNeural probes are sophisticated electrophysiological tools used for intra-cortical recording and stimulation. These microelectrode arrays, designed to penetrate and interface the brain from within, contribute at the forefront of basic and clinical neuroscience. However, one of the challenges and currently most significant limitations is their ‘seamless’ long-term integration into the surrounding brain tissue. Following implantation, which is typically accompanied by bleeding, the tissue responds with a scarring process, resulting in a gliotic region closest to the probe. This glial scarring is often associated with neuroinflammation, neurodegeneration, and a leaky blood–brain interface (BBI). The engineering progress on minimizing this reaction in the form of improved materials, microfabrication, and surgical techniques is summarized in this review. As research over the past decade has progressed towards a more detailed understanding of the nature of this biological response, it is time to pose the question: Are penetrating probes completely free from glial scarring at all possible?

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Li, Ping, Zhao-Qian Teng, and Chang-Mei Liu. "Extrinsic and Intrinsic Regulation of Axon Regeneration by MicroRNAs after Spinal Cord Injury." Neural Plasticity 2016 (2016): 1–11. http://dx.doi.org/10.1155/2016/1279051.

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Spinal cord injury is a devastating disease which disrupts the connections between the brain and spinal cord, often resulting in the loss of sensory and motor function below the lesion site. Most injured neurons fail to regenerate in the central nervous system after injury. Multiple intrinsic and extrinsic factors contribute to the general failure of axonal regeneration after injury. MicroRNAs can modulate multiple genes’ expression and are tightly controlled during nerve development or the injury process. Evidence has demonstrated that microRNAs and their signaling pathways play important roles in mediating axon regeneration and glial scar formation after spinal cord injury. This article reviews the role and mechanism of differentially expressed microRNAs in regulating axon regeneration and glial scar formation after spinal cord injury, as well as their therapeutic potential for promoting axonal regeneration and repair of the injured spinal cord.

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Cloutier, Frank, Ilse Sears-Kraxberger, Krista Keachie, and Hans S. Keirstead. "Immunological Demyelination Triggers Macrophage/Microglial Cells Activation without Inducing Astrogliosis." Clinical and Developmental Immunology 2013 (2013): 1–14. http://dx.doi.org/10.1155/2013/812456.

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The glial scar formed by reactive astrocytes and axon growth inhibitors associated with myelin play important roles in the failure of axonal regeneration following central nervous system (CNS) injury. Our laboratory has previously demonstrated that immunological demyelination of the CNS facilitates regeneration of severed axons following spinal cord injury. In the present study, we evaluate whether immunological demyelination is accompanied with astrogliosis. We compared the astrogliosis and macrophage/microglial cell responses 7 days after either immunological demyelination or a stab injury to the dorsal funiculus. Both lesions induced a strong activated macrophage/microglial cells response which was significantly higher within regions of immunological demyelination. However, immunological demyelination regions were not accompanied by astrogliosis compared to stab injury that induced astrogliosis which extended several millimeters above and below the lesions, evidenced by astroglial hypertrophy, formation of a glial scar, and upregulation of intermediate filaments glial fibrillary acidic protein (GFAP). Moreover, a stab or a hemisection lesion directly within immunological demyelination regions did not induced astrogliosis within the immunological demyelination region. These results suggest that immunological demyelination creates a unique environment in which astrocytes do not form a glial scar and provides a unique model to understand the putative interaction between astrocytes and activated macrophage/microglial cells.

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Saadoun, S. "Involvement of aquaporin-4 in astroglial cell migration and glial scar formation." Journal of Cell Science 118, no. 24 (December 15, 2005): 5691–98. http://dx.doi.org/10.1242/jcs.02680.

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Hsu, J. Y. C., L. Y. W. Bourguignon, C. M. Adams, K. Peyrollier, H. Zhang, T. Fandel, C. L. Cun, Z. Werb, and L. J. Noble-Haeusslein. "Matrix Metalloproteinase-9 Facilitates Glial Scar Formation in the Injured Spinal Cord." Journal of Neuroscience 28, no. 50 (December 10, 2008): 13467–77. http://dx.doi.org/10.1523/jneurosci.2287-08.2008.

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Leme, Ricardo José de Almeida, and Gerson Chadi. "Distant microglial and astroglial activation secondary to experimental spinal cord lesion." Arquivos de Neuro-Psiquiatria 59, no. 3A (September 2001): 483–92. http://dx.doi.org/10.1590/s0004-282x2001000400002.

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This paper analysed whether glial responses following a spinal cord lesion is restricted to a scar formation close to the wound or they might be also related to widespread paracrine trophic events in the entire cord. Spinal cord hemitransection was performed in adult rats at the thoracic level. Seven days and three months later the spinal cords were removed and submitted to immunohistochemistry of glial fibrillary acidic protein (GFAP) and OX42, markers for astrocytes and microglia, as well as of basic fibroblast growth factor (bFGF), an astroglial neurotrophic factor. Computer assisted image analysis was employed in the quantification of the immunoreactivity changes. At the lesion site an increased number of GFAP positive astrocytes and OX42 positive phagocytic cells characterized a dense scar formation by seven days, which was further augmented after three months. Morphometric analysis of the area and microdensitometric analysis of the intensity of the GFAP and OX42 immunoreactivities showed reactive astrocytes and microglia in the entire spinal cord white and gray matters 7 days and 3 months after surgery. Double immunofluorescence demonstrated increased bFGF immunostaining in reactive astrocytes. The results indicated that glial reaction close to an injury site of the spinal cord is related to wounding and repair events. Although gliosis constitutes a barrier to axonal regeneration, glial activation far from the lesion may contribute to neuronal trophism and plasticity in the lesioned spinal cord favoring neuronal maintenance and fiber outgrowth.

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Robel, Stefanie. "Astroglial Scarring and Seizures." Neuroscientist 23, no. 2 (July 7, 2016): 152–68. http://dx.doi.org/10.1177/1073858416645498.

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Epilepsy is among the most prevalent chronic neurological diseases and affects an estimated 2.2 million people in the United States alone. About one third of patients are resistant to currently available antiepileptic drugs, which are exclusively targeting neuronal function. Yet, reactive astrocytes have emerged as potential contributors to neuronal hyperexcitability and seizures. Astrocytes react to any kind of CNS insult with a range of cellular adjustments to form a scar and protect uninjured brain regions. This process changes astrocyte physiology and can affect neuronal network function in various ways. Traumatic brain injury and stroke, both conditions that trigger astroglial scar formation, are leading causes of acquired epilepsies and surgical removal of this glial scar in patients with drug-resistant epilepsy can alleviate the seizures. This review will summarize the currently available evidence suggesting that epilepsy is not a disease of neurons alone, but that astrocytes, glial cells in the brain, can be major contributors to the disease, especially when they adopt a reactive state in response to central nervous system insult.

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Yeh, Jue-Zong, Ding-Han Wang, Juin-Hong Cherng, Yi-Wen Wang, Gang-Yi Fan, Nien-Hsien Liou, Jiang-Chuan Liu, and Chung-Hsing Chou. "A Collagen-Based Scaffold for Promoting Neural Plasticity in a Rat Model of Spinal Cord Injury." Polymers 12, no. 10 (September 29, 2020): 2245. http://dx.doi.org/10.3390/polym12102245.

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In spinal cord injury (SCI) therapy, glial scarring formed by activated astrocytes is a primary problem that needs to be solved to enhance axonal regeneration. In this study, we developed and used a collagen scaffold for glial scar replacement to create an appropriate environment in an SCI rat model and determined whether neural plasticity can be manipulated using this approach. We used four experimental groups, as follows: SCI-collagen scaffold, SCI control, normal spinal cord-collagen scaffold, and normal control. The collagen scaffold showed excellent in vitro and in vivo biocompatibility. Immunofluorescence staining revealed increased expression of neurofilament and fibronectin and reduced expression of glial fibrillary acidic protein and anti-chondroitin sulfate in the collagen scaffold-treated SCI rats at 1 and 4 weeks post-implantation compared with that in untreated SCI control. This indicates that the collagen scaffold implantation promoted neuronal survival and axonal growth within the injured site and prevented glial scar formation by controlling astrocyte production for their normal functioning. Our study highlights the feasibility of using the collagen scaffold in SCI repair. The collagen scaffold was found to exert beneficial effects on neuronal activity and may help in manipulating synaptic plasticity, implying its great potential for clinical application in SCI.

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Hayashi, Noriko, Seiji Miyata, Yutaka Kariya, Ryo Takano, Saburo Hara, and Kaeko Kamei. "Attenuation of glial scar formation in the injured rat brain by heparin oligosaccharides." Neuroscience Research 49, no. 1 (May 2004): 19–27. http://dx.doi.org/10.1016/j.neures.2004.01.007.

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Romero-Ramírez, Lorenzo, Manuel Nieto-Sampedro, and MAsunción Barreda-Manso. "All roads go to Salubrinal: endoplasmic reticulum stress, neuroprotection and glial scar formation." Neural Regeneration Research 10, no. 12 (2015): 1926. http://dx.doi.org/10.4103/1673-5374.169619.

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Zhao, Lina, Xianyu Zhang, and Chunhai Zhang. "Methimazole Inhibits the Expression of GFAP and the Migration of Astrocyte in Scratched Wound Model In Vitro." Mediators of Inflammation 2020 (April 13, 2020): 1–7. http://dx.doi.org/10.1155/2020/4027470.

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Astrocytes respond to central nervous system (CNS) insults with varieties of changes, such as cellular hypertrophy, migration, proliferation, scar formation, and upregulation of glial fibrillary acidic protein (GFAP) expression. While scar formation plays a very important role in wound healing and prevents further bleeding by forming a physical barrier, it is also one of key features of CNS injury, resulting in glial scar formation (astrogliosis), which is closely related to treatment resistant epilepsy, chronic pain, and other devastating diseases. Therefore, slowing the astrocytic activation process may give a time window of axonal growth after the CNS injury. However, the underlying mechanism of astrocytic activation remains unclear, and there is no effective therapeutic strategy to attenuate the activation process. Here, we found that methimazole could effectively inhibit the GFAP expression in physiological and pathological conditions. Moreover, we scratched primary cultures of cerebral cortical astrocytes with and without methimazole pretreatment and investigated whether methimazole could slow the healing process in these cultures. We found that methimazole could inhibit the GFAP protein expression in scratched astrocytes and prolong the latency of wound healing in cultures. We also measured the phosphorylation of extracellular signal-regulated kinase (ERK) in these cultures and found that methimazole could significantly inhibit the scratch-induced GFAP upregulation. For the first time, our study demonstrated that methimazole might be a possible compound that could inhibit the astrocytic activation following CNS injury by reducing the ERK phosphorylation in astrocytes.

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Song, Byeong Gwan, Su Yeon Kwon, Jae Won Kyung, Eun Ji Roh, Hyemin Choi, Chang Su Lim, Seong Bae An, Seil Sohn, and Inbo Han. "Synaptic Cell Adhesion Molecule 3 (SynCAM3) Deletion Promotes Recovery from Spinal Cord Injury by Limiting Glial Scar Formation." International Journal of Molecular Sciences 23, no. 11 (June 1, 2022): 6218. http://dx.doi.org/10.3390/ijms23116218.

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Synaptic cell adhesion molecules (SynCAMs) play an important role in the formation and maintenance of synapses and the regulation of synaptic plasticity. SynCAM3 is expressed in the synaptic cleft of the central nervous system (CNS) and is involved in the connection between axons and astrocytes. We hypothesized that SynCAM3 may be related to the astrocytic scar (glial scar, the most important factor of CNS injury treatment) through extracellular matrix (ECM) reconstitution. Thus, we investigated the influence of the selective removal of SynCAM3 on the outcomes of spinal cord injury (SCI). SynCAM3 knock-out (KO) mice were subjected to moderate compression injury of the lower thoracic spinal cord using wild-type (WT) (C57BL/6JJc1) mice as controls. Single-cell RNA sequencing analysis over time, quantitative real-time polymerase chain reaction (qRT-PCR) analysis, and immunohistochemistry (IHC) showed reduced scar formation in SynCAM3 KO mice compared to WT mice. SynCAM3 KO mice showed improved functional recovery from SCI by preventing the transformation of reactive astrocytes into scar-forming astrocytes, resulting in improved ECM reconstitution at four weeks after injury. Our findings suggest that SynCAM3 could be a novel therapeutic target for SCI.

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Sun, Daniel, and Tatjana C. Jakobs. "Structural Remodeling of Astrocytes in the Injured CNS." Neuroscientist 18, no. 6 (October 7, 2011): 567–88. http://dx.doi.org/10.1177/1073858411423441.

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Astrocytes respond to all forms of CNS insult and disease by becoming reactive, a nonspecific but highly characteristic response that involves various morphological and molecular changes. Probably the most recognized aspect of reactive astrocytes is the formation of a glial scar that impedes axon regeneration. Although the reactive phenotype was first suggested more than 100 years ago based on morphological changes, the remodeling process is not well understood. We know little about the actual structure of a reactive astrocyte, how an astrocyte remodels during the progression of an insult, and how populations of these cells reorganize to form the glial scar. New methods of labeling astrocytes, along with transgenic mice, allow the complete morphology of reactive astrocytes to be visualized. Recent studies show that reactivity can induce a remarkable change in the shape of a single astrocyte, that not all astrocytes react in the same way, and that there is plasticity in the reactive response.

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Parry, Phillip V., and Johnathan A. Engh. "Promotion of Neuronal Recovery Following Experimental SCI via Direct Inhibition of Glial Scar Formation." Neurosurgery 70, no. 6 (June 2012): N10—N11. http://dx.doi.org/10.1227/01.neu.0000414941.18107.47.

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Zhu, Yong-Ming, Xue Gao, Yong Ni, Wei Li, Thomas A. Kent, Shi-Gang Qiao, Chen Wang, Xiao-Xuan Xu, and Hui-Ling Zhang. "Sevoflurane postconditioning attenuates reactive astrogliosis and glial scar formation after ischemia–reperfusion brain injury." Neuroscience 356 (July 2017): 125–41. http://dx.doi.org/10.1016/j.neuroscience.2017.05.004.

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Wang, Yu-Fu, Jia-Ning Zu, Jing Li, Chao Chen, Chun-Yang Xi, and Jing-Long Yan. "Curcumin promotes the spinal cord repair via inhibition of glial scar formation and inflammation." Neuroscience Letters 560 (February 2014): 51–56. http://dx.doi.org/10.1016/j.neulet.2013.11.050.

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Uesugi, Masafumi, Yoshitoshi Kasuva, Hiroshi Hama, Tomoh Masaki, and Katsutoshi Goto. "The Participation of Endogenous ET-1 in Glial Scar formation after Spinal Cord Injury." Japanese Journal of Pharmacology 73 (1997): 112. http://dx.doi.org/10.1016/s0021-5198(19)44953-6.

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Okuda, Akinori, Noriko Horii-Hayashi, Takayo Sasagawa, Takamasa Shimizu, Hideki Shigematsu, Eiichiro Iwata, Yasuhiko Morimoto, et al. "Bone marrow stromal cell sheets may promote axonal regeneration and functional recovery with suppression of glial scar formation after spinal cord transection injury in rats." Journal of Neurosurgery: Spine 26, no. 3 (March 2017): 388–95. http://dx.doi.org/10.3171/2016.8.spine16250.

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OBJECTIVE Transplantation of bone marrow stromal cells (BMSCs) is a theoretical potential as a therapeutic strategy in the treatment of spinal cord injury (SCI). Although a scaffold is sometimes used for retaining transplanted cells in damaged tissue, it is also known to induce redundant immunoreactions during the degradation processes. In this study, the authors prepared cell sheets made of BMSCs, which are transplantable without a scaffold, and investigated their effects on axonal regeneration, glial scar formation, and functional recovery in a completely transected SCI model in rats. METHODS BMSC sheets were prepared from the bone marrow of female Fischer 344 rats using ascorbic acid and were cryopreserved until the day of transplantation. A gelatin sponge (GS), as a control, or BMSC sheet was transplanted into a 2-mm-sized defect of the spinal cord at the T-8 level. Axonal regeneration and glial scar formation were assessed 2 and 8 weeks after transplantation by immunohistochemical analyses using anti-Tuj1 and glial fibrillary acidic protein (GFAP) antibodies, respectively. Locomotor function was evaluated using the Basso, Beattie, and Bresnahan scale. RESULTS The BMSC sheets promoted axonal regeneration at 2 weeks after transplantation, but there was no significant difference in the number of Tuj1-positive axons between the sheet- and GS-transplanted groups. At 8 weeks after transplantation, Tuj1-positive axons elongated across the sheet, and their numbers were significantly greater in the sheet group than in the GS group. The areas of GFAP-positive glial scars in the sheet group were significantly reduced compared with those of the GS group at both time points. Finally, hindlimb locomotor function was ameliorated in the sheet group at 4 and 8 weeks after transplantation. CONCLUSIONS The results of the present study indicate that an ascorbic acid–induced BMSC sheet is effective in the treatment of SCI and enables autologous transplantation without requiring a scaffold.

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Zhang, Rongyi, Junhua Wang, Qingwen Deng, Xingru Xiao, Xiang Zeng, Biqin Lai, Ge Li, et al. "Mesenchymal Stem Cells Combined With Electroacupuncture Treatment Regulate the Subpopulation of Macrophages and Astrocytes to Facilitate Axonal Regeneration in Transected Spinal Cord." Neurospine 20, no. 4 (December 31, 2023): 1358–79. http://dx.doi.org/10.14245/ns.2346824.412.

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Objective: Herein, we investigated whether mesenchymal stem cells (MSCs) transplantation combined with electroacupuncture (EA) treatment could decrease the proportion of proinflammatory microglia/macrophages and neurotoxic A1 reactive astrocytes and inhibit glial scar formation to enhance axonal regeneration after spinal cord injury (SCI).Methods: Adult rats were divided into 5 groups after complete transection of the spinal cord at the T10 level: a control group, a nonacupoint EA (NA-EA) group, an EA group, an MSC group, and an MSCs+EA group. Immunofluorescence labeling, quantitative real-time polymerase chain reaction, enzyme-linked immunosorbent assay, and Western blots were performed.Results: The results showed that MSCs+EA treatment reduced the proportion of proinflammatory M1 subtype microglia/macrophages, but increased the differentiation of anti-inflammatory M2 phenotype cells, thereby suppressing the mRNA and protein expression of proinflammatory cytokines (tumor necrosis factor-α and IL-1β) and increasing the expression of an anti-inflammatory cytokine (interleukin [IL]-10) on days 7 and 14 after SCI. The changes in expression correlated with the attenuated neurotoxic A1 reactive astrocytes and glial scar, which in turn facilitated the axonal regeneration of the injured spinal cord. <i>In vitro</i>, the proinflammatory cytokines increased the level of proliferation of astrocytes and increased the expression levels of C3, glial fibrillary acidic protein, and chondroitin sulfate proteoglycan. These effects were blocked by administering inhibitors of ErbB1 and signal transducer and activator of transcription 3 (STAT3) (AG1478 and AG490) and IL-10.Conclusion: These findings showed that MSCs+EA treatment synergistically regulated the microglia/macrophage subpopulation to reduce inflammation, the formation of neurotoxic A1 astrocytes, and glial scars. This was achieved by downregulating the ErbB1-STAT3 signal pathway, thereby providing a favorable microenvironment conducive to axonal regeneration after SCI.

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Pasterkamp, R. Jeroen, and Joost Verhaagen. "Semaphorins in axon regeneration: developmental guidance molecules gone wrong?" Philosophical Transactions of the Royal Society B: Biological Sciences 361, no. 1473 (July 28, 2006): 1499–511. http://dx.doi.org/10.1098/rstb.2006.1892.

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Semaphorins are developmental axon guidance cues that continue to be expressed during adulthood and are regulated by neural injury. During the formation of the nervous system, repulsive semaphorins guide axons to their targets by restricting and channelling their growth. They affect the growth cone cytoskeleton through interactions with receptor complexes that are linked to a complicated intracellular signal transduction network. Following injury, regenerating axons stop growing when they reach the border of the glial-fibrotic scar, in part because they encounter a potent molecular barrier that inhibits growth cone extension. A number of secreted semaphorins are expressed in the glial-fibrotic scar and at least one transmembrane semaphorin is upregulated in oligodendrocytes surrounding the lesion site. Semaphorin receptors, and many of the signal transduction components required for semaphorin signalling, are present in injured central nervous system neurons. Here, we review evidence that supports a critical role for semaphorin signalling in axon regeneration, and highlight a number of challenges that lie ahead with respect to advancing our understanding of semaphorin function in the normal and injured adult nervous system.

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Zhang, Ce, Jianning Kang, Xiaodi Zhang, Ying Zhang, Nana Huang, and Bin Ning. "Spatiotemporal dynamics of the cellular components involved in glial scar formation following spinal cord injury." Biomedicine & Pharmacotherapy 153 (September 2022): 113500. http://dx.doi.org/10.1016/j.biopha.2022.113500.

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Li, Yi, Jian Wu, Zhen-Yu Zhu, Zhi-Wei Fan, Ying Chen, and Ri-Yun Yang. "Downregulation of EphB2 by RNA interference attenuates glial/fibrotic scar formation and promotes axon growth." Neural Regeneration Research 17, no. 2 (2022): 362. http://dx.doi.org/10.4103/1673-5374.317988.

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Tysseling-Mattiace, V. M., V. Sahni, K. L. Niece, D. Birch, C. Czeisler, M. G. Fehlings, S. I. Stupp, and J. A. Kessler. "Self-Assembling Nanofibers Inhibit Glial Scar Formation and Promote Axon Elongation after Spinal Cord Injury." Journal of Neuroscience 28, no. 14 (April 2, 2008): 3814–23. http://dx.doi.org/10.1523/jneurosci.0143-08.2008.

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Journal articles on the topic 'Glial scar formation'

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