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Journal articles on the topic 'Olfactory nerve – Regeneration'

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Author: Grafiati

Published: 4 June 2021

Last updated: 19 February 2022

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1

Jiang, Rong-San, and Yu-Yu Lu. "Functional Olfactory Nerve Regeneration Demonstrated by Thallium-201 Olfacto-Scintigraphy in Patients with Traumatic Anosmia: A Case Report." Case Reports in Otolaryngology 2019 (November 16, 2019): 1–7. http://dx.doi.org/10.1155/2019/1069741.

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Head trauma is one of the most common etiologies of olfactory dysfunction. It is difficult to use either the olfactory function test or magnetic resonance imaging to directly assess the course of damage to olfactory nerves. Thallium-201 (201Tl) olfacto-scintigraphy has been shown to be an able means for objectively assessing the olfactory nerve transport function. It is expected to be used to evaluate olfactory nerve regeneration after damage to the olfactory nerves. However, no such result has been reported. We present a patient who lost his olfactory function after experiencing head trauma. When his olfactory function remained anosmic, a 201Tl olfacto-scintigraphy showed no migration of 201Tl from the nasal mucosa to the olfactory bulb. After treatment with medicines and olfactory training, his olfactory function improved. A second 201Tl olfacto-scintigraphy showed an increased migration of 201Tl from the nasal mucosa to the olfactory bulb.

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2

Li, Manyi, Qiubei Zhu, and Jisheng Liu. "Olfactory ensheathing cells in facial nerve regeneration." Brazilian Journal of Otorhinolaryngology 86, no. 5 (September 2020): 525–33. http://dx.doi.org/10.1016/j.bjorl.2018.07.006.

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3

Alvites, Rui D., Mariana V. Branquinho, Ana C. Sousa, Irina Amorim, Rui Magalhães, Filipa João, Diogo Almeida, et al. "Combined Use of Chitosan and Olfactory Mucosa Mesenchymal Stem/Stromal Cells to Promote Peripheral Nerve Regeneration In Vivo." Stem Cells International 2021 (January 2, 2021): 1–32. http://dx.doi.org/10.1155/2021/6613029.

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Peripheral nerve injury remains a clinical challenge with severe physiological and functional consequences. Despite the existence of multiple possible therapeutic approaches, until now, there is no consensus regarding the advantages of each option or the best methodology in promoting nerve regeneration. Regenerative medicine is a promise to overcome this medical limitation, and in this work, chitosan nerve guide conduits and olfactory mucosa mesenchymal stem/stromal cells were applied in different therapeutic combinations to promote regeneration in sciatic nerves after neurotmesis injury. Over 20 weeks, the intervened animals were subjected to a regular functional assessment (determination of motor performance, nociception, and sciatic indexes), and after this period, they were evaluated kinematically and the sciatic nerves and cranial tibial muscles were evaluated stereologically and histomorphometrically, respectively. The results obtained allowed confirming the beneficial effects of using these therapeutic approaches. The use of chitosan NGCs and cells resulted in better motor performance, better sciatic indexes, and lower gait dysfunction after 20 weeks. The use of only NGGs demonstrated better nociceptive recoveries. The stereological evaluation of the sciatic nerve revealed identical values in the different parameters for all therapeutic groups. In the muscle histomorphometric evaluation, the groups treated with NGCs and cells showed results close to those of the group that received traditional sutures, the one with the best final values. The therapeutic combinations studied show promising outcomes and should be the target of new future works to overcome some irregularities found in the results and establish the combination of nerve guidance conduits and olfactory mucosa mesenchymal stem/stromal cells as viable options in the treatment of peripheral nerves after injury.

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4

Verdú, Enrique, Xavier Navarro, Graciela Gudiño-Cabrera, Francisco J. Rodríguez, Dolores Ceballos, Antoni Valero, and Manuel Nieto-Sampedro. "Olfactory bulb ensheathing cells enhance peripheral nerve regeneration." NeuroReport 10, no. 5 (April 1999): 1097–101. http://dx.doi.org/10.1097/00001756-199904060-00035.

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5

Nathan, Britto P., Rafia Nisar, Jody Short, Shari Randall, Elin Grissom, Gwen Griffin, Paul V. Switzer, and Robert G. Struble. "Delayed olfactory nerve regeneration in ApoE-deficient mice." Brain Research 1041, no. 1 (April 2005): 87–94. http://dx.doi.org/10.1016/j.brainres.2005.02.011.

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6

Yamada, Kentaro, Hideaki Shiga, Takuya Noda, Masayuki Harita, Tomoko Ishikura, Yukari Nakamura, Toshihisa Hatta, Hiromi Sakata-Haga, Hiroki Shimada, and Takaki Miwa. "The Impact of Ovariectomy on Olfactory Neuron Regeneration in Mice." Chemical Senses 45, no. 3 (February 3, 2020): 203–9. http://dx.doi.org/10.1093/chemse/bjaa005.

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Abstract Estrogen has been shown to affect differentiation and proliferation as a mitogen in various neural systems. Olfactory receptor cells are unique within the nervous system, and have the ability to regenerate even after an individual has reached maturity. Olfactory receptor cells also regenerate after experimentally induced degeneration. The purpose of this study is to observe the influence of estrogen depletion induced by ovariectomy on olfactory nerve regeneration. Female mice underwent bilateral ovariectomy at 8 weeks of age and received intraperitoneal administration of methimazole 1 week later. At 2, 4, and 6 weeks after methimazole administration, the olfactory mucosa was analyzed histochemically to determine olfactory epithelium (OE) thickness, olfactory marker protein distribution, and Ki-67 immunoreactivity. Furthermore, 2 weeks after ovariectomy, trkA protein distribution in the OE and nerve growth factor (NGF) levels in the olfactory bulb were determined by immunohistochemistry and enzyme-linked immunosorbent assay, respectively. Our results showed that in ovariectomized mice OMP, Ki-67, and trkA-immunopositive cells expression decreased at 2 weeks after methimazole injection, a time point at which regeneration is underway. At this same time point, although NGF production in the olfactory bulb had increased before methimazole administration, no differences were observed between the ovx and control groups. These results suggest that estrogen depletion induces a suppressive effect on regeneration of olfactory neurons, and that estrogen may have a potential use in the treatment of sensorineural olfactory dysfunction.

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7

Radtke, Christine, Masanori Sasaki, Karen L. Lankford, Vittorio Gallo, and Jeffery D. Kocsis. "CNPase Expression in Olfactory Ensheathing Cells." Journal of Biomedicine and Biotechnology 2011 (2011): 1–8. http://dx.doi.org/10.1155/2011/608496.

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A large body of work supports the proposal that transplantation of olfactory ensheathing cells (OECs) into nerve or spinal cord injuries can promote axonal regeneration and remyelination. Yet, some investigators have questioned whether the transplanted OECs associate with axons and form peripheral myelin, or if they recruit endogenous Schwann cells that form myelin. Olfactory bulbs from transgenic mice expressing the enhanced green fluorescent protein (eGFP) under the control of the 2-3-cyclic nucleotide 3-phosphodiesterase (CNPase) promoter were studied. CNPase is expressed in myelin-forming cells throughout their lineage. We examined CNPase expression in both in situ in the olfactory bulb andin vitroto determine if OECs express CNPase commensurate with their myelination potential. eGFP was observed in the outer nerve layer of the olfactory bulb. Dissociated OECs maintained in culture had both intense eGFP expression and CNPase immunostaining. Transplantation of OECs into transected peripheral nerve longitudinally associated with the regenerated axons. These data indicate that OECs in the outer nerve layer of the olfactory bulb of CNPase transgenic mice express CNPase. Thus, while OECs do not normally form myelin on olfactory nerve axons, their expression of CNPase is commensurate with their potential to form myelin when transplanted into injured peripheral nerve.

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8

Zippel, Hans Peter. "In goldfish the discriminative ability for odours persists after reduction of the olfactory epithelium, and rapidly returns after olfactory nerve axotomy and crossing bulbs." Philosophical Transactions of the Royal Society of London. Series B: Biological Sciences 355, no. 1401 (September 29, 2000): 1219–23. http://dx.doi.org/10.1098/rstb.2000.0671.

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Goldfish are ideal vertebrates for the study of regeneration within the peripheral and the central olfactory system. The present behavioural investigations studied the effects of bilateral lesions on the animals' ability to qualitatively discriminate two amino acids (107 -6 M) and their performance in two more difficult tasks: (i) rewarded amino acid applied in a lower concentration, and (ii) rewarded stimulus contaminated. A 50 and 85% reduction of the olfactory epithelium resulted in no recordable behavioural deficit. After axotomy of olfactory nerves and lateral olfactory tractotomy, fishes were anosmic for seven to ten days. Following replacement of sensory cells in the epithelium, and after regeneration of olfactory tract fibres a full functional recovery, i.e. a highly specific regeneration, was recorded. After three surgical modifications of the olfactory bulbs' position, (i) crossing olfactory tracts and bulbs, (ii) crossing tracts and turning bulbs, and (iii) turning bulbs upside down, a full functional recovery was recorded for amino-acid discrimination in a similar concentration. A permanent, and similar slight deficit was, however, found during application of different concentrations, and of contaminated stimuli when medial lateral halves of the bulb were in ‘incorrect’ position (i) and (iii), or olfactory bulbs were positioned in the vicinity of the contralateral epithelium (i) and (ii).

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9

Deng, Yue, Jing-Ping Fan, Jian Gu, He Xu, Ya-Ping Xu, Huan-Hai Liu, Jun-Tian Lang, Xiao-Ping Chen, and Wei-Hua Xu. "Olfactory ensheathing cells promote nerve regeneration and functional recovery after facial nerve defects." Neural Regeneration Research 14, no. 1 (2019): 124. http://dx.doi.org/10.4103/1673-5374.243717.

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10

Radtke, Christine, Ayal A. Aizer, Samuel K. Agulian, Karen L. Lankford, Peter M. Vogt, and Jeffery D. Kocsis. "Transplantation of olfactory ensheathing cells enhances peripheral nerve regeneration after microsurgical nerve repair." Brain Research 1254 (February 2009): 10–17. http://dx.doi.org/10.1016/j.brainres.2008.11.036.

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11

Yoshino, Jun, and Shin Tochinai. "Functional regeneration of the olfactory bulb requires reconnection to the olfactory nerve in Xenopus larvae." Development, Growth & Differentiation 48, no. 1 (February 8, 2006): 15–24. http://dx.doi.org/10.1111/j.1440-169x.2006.00840.x.

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12

Costanzo, Richard M. "Neural regeneration and functional reconnection following olfactory nerve transection in hamster." Brain Research 361, no. 1-2 (December 1985): 258–66. http://dx.doi.org/10.1016/0006-8993(85)91297-1.

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13

Lee, Jong-Yoon, Young-Ho Kim, Boo-Young Kim, Dae-Hyun Jang, Sung-Wook Choi, So-Hyun Joen, Hyungyun Kim, and Sang-Uk Lee. "Peripheral Nerve Regeneration Using a Nerve Conduit with Olfactory Ensheathing Cells in a Rat Model." Tissue Engineering and Regenerative Medicine 18, no. 3 (January 30, 2021): 453–65. http://dx.doi.org/10.1007/s13770-020-00326-9.

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14

Gong, Shun, Hai Jin, Danfeng Zhang, Wei Zou, Chunhui Wang, Zhenxing Li, Rongbin Chen, Yan Dong, and Lijun Hou. "The Therapeutic Effects after Transplantation of Whole-Layer Olfactory Mucosa in Rats with Optic Nerve Injury." BioMed Research International 2018 (2018): 1–8. http://dx.doi.org/10.1155/2018/6069756.

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Background. Existing evidence suggests the potential therapy of transplanting olfactory ensheathing cells (OEC) either alone or in combination with neurotrophic factors or other cell types in optic nerve injury (ONI). However, clinical use of autologous OEC in the acute stages of ONI is not possible. On the other hand, acute application of heterologous transplantation may bring the issue of immune rejection. The olfactory mucosa (OM) with OEC in the lamina propria layer is located in the upper region of the nasal cavity and is easy to dissect under nasal endoscopy, which makes it a candidate as autograft material in acute stages of ONI. To investigate the potential of the OM on the protection of injured neurons and on the promotion of axonal regeneration, we developed a transplantation of syngenic OM in rats with ONI model. Methods. After the right optic nerve was crushed in Lewis rats, pieces of syngenic whole-layer OM were transplanted into the lesion. Rats undergoing phosphate buffered saline (PBS) injection were used as negative controls (NC). The authors evaluated the regeneration of retinal ganglion cells (RGCs) and axons for 3, 7, 14, and 28 days after transplantation. Obtained retinas and optic nerves were analyzed histologically. Results. Transplantations of OM significantly promoted the survival of retinal ganglion cells (RGCs) and axonal growth of RGCs compared with PBS alone. Moreover, OM group was associated with higher expression of GAP-43 in comparison with the PBS group. In addition to the potential effects on RGCs, transplantations of OM significantly decreased the expression of GFAP in the retinas, suggesting inhibiting astrocyte activation. Conclusions. Transplantation of whole-layer OM in rats contributes to the neuronal survival and axon regeneration after ONI.

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15

MASUKAWA, LEONA M., BRITTA HEDLUND, and GORDON M. SHEPHERD. "Changes in Excitable Properties of Olfactory Receptor Neurons Associated with Nerve Regeneration." Annals of the New York Academy of Sciences 510, no. 1 Olfaction and (November 1987): 475–77. http://dx.doi.org/10.1111/j.1749-6632.1987.tb43595.x.

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16

Goulart, Camila Oliveira, Daniella de Freitas Pereira Ângelo Durço, Lítia Alves de Carvalho, Júlia Teixeira Oliveira, Lucinéia Alves, Leny A. Cavalcante, and Ana Maria Blanco Martinez. "Olfactory ensheathing glia cell therapy and tubular conduit enhance nerve regeneration after mouse sciatic nerve transection." Brain Research 1650 (November 2016): 243–51. http://dx.doi.org/10.1016/j.brainres.2016.09.021.

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17

Collins, Andrew, Daqing Li, Stephen B. Mcmahon, Geoffrey Raisman, and Ying Li. "Transplantation of Cultured Olfactory Bulb Cells Prevents Abnormal Sensory Responses during Recovery from Dorsal Root Avulsion in the Rat." Cell Transplantation 26, no. 5 (May 2017): 913–24. http://dx.doi.org/10.3727/096368917x695353.

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The central branches of the C7 and C8 dorsal roots were avulsed close to their entry point into the spinal cord in adult rats. The forepaw responses to heat and cold stimuli were tested at 1, 2, and 3 weeks after injury. Over this period, the paws were sensitive to both stimuli at 1-2 weeks and returned toward normal at 3 weeks. Immunohistology showed no evidence of axonal regeneration into the spinal cord in a control group of rats with avulsion only, implying that adjacent dorsal roots and their corresponding dermatomes were involved in the recovery. In a further group of rats, a mixture of bulbar olfactory ensheathing cells and olfactory nerve fibroblasts were transplanted into the gap between the avulsed roots and the spinal cord at the time of avulsion. These rats showed no evidence of either loss of sensation or exaggerated responses to stimuli at any of the time points from 1 to 3 weeks. Immunohistology showed that the transplanted cells formed a complete bridge, and the central branches of the dorsal root fibers had regenerated into the dorsal horn of the spinal cord. These regenerating axons, including Tuj1 and CGRP immunoreactive fibers, were ensheathed by the olfactory ensheathing cells. This confirms our previous demonstration of central regeneration by these transplants and suggests that such transplants may provide a useful means to prevent the development of abnormal sensations such as allodynia after spinal root lesions.

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18

Grzesiak, Jakub, Ryszard Fryczkowski, Anna Lis, Dariusz Szarek, Jadwiga Laska, and Krzysztof Marycz. "Characterization of Olfactory Ensheathing Glial Cells Cultured on Polyurethane/Polylactide Electrospun Nonwovens." International Journal of Polymer Science 2015 (2015): 1–10. http://dx.doi.org/10.1155/2015/908328.

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The aim of this research was to evaluate novel biomaterials for neural regeneration. The investigated materials were composed of polyurethane (PU) and polylactide (PLDL) blended at three different w/w ratios, that is, 5/5, 6/4, and 8/2 of PU/PLDL. Ultrathin fibrous scaffolds were prepared using electrospinning. The scaffolds were investigated for their applicability for nerve regeneration by culturing rat olfactory ensheathing glial cells. Cells were cultured on the materials for seven days, during which cellular morphology, phenotype, and metabolic activity were analysed. SEM analysis of the fabricated fibrous scaffolds showed fibers of a diameter mainly lower than 600 μm with unimportant volume of protrusions situated along the fibers, with nonsignificant differences between all analysed materials. Cells cultured on the materials showed differences in their morphology and metabolic activity, depending on the blend composition. The most proper morphology, with numerous p75+and GFAP+cells present, was observed in the sample 6/4, whereas the highest metabolic activity was measured in the sample 5/5. However, none of the investigated samples showed cytotoxicity or negatively influenced cellular morphology. Therefore, the novel electrospun fibrous materials may be considered for regenerative medicine applications, and especially when contacting with highly sensitive nervous cells.

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19

Bartolomei, Juan C., and Charles A. Greer. "Olfactory Ensheathing Cells: Bridging the Gap in Spinal Cord Injury." Neurosurgery 47, no. 5 (November 1, 2000): 1057–69. http://dx.doi.org/10.1097/00006123-200011000-00006.

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Abstract SPINAL CORD INJURY (SCI) continues to be an insidious and challenging problem for scientists and clinicians. Recent neuroscientific advances have changed the pessimistic notion that axons are not capable of significant extension after transection. The challenges of recovering from SCI have been broadly divided into four areas: 1) cell survival; 2) axon regeneration (growth); 3) correct targeting by growing axons; and 4) establishment of correct and functional synaptic appositions. After acute SCI, there seems to be a therapeutic window of opportunity within which the devastating consequences of the secondary injury can be ameliorated. This is supported by several observations in which apoptotic glial cells have been identified up to 1 week after acute SCI. Moreover, autopsy studies have identified anatomically preserved but unmyelinated axons that could potentially subserve normal physiological properties. These observations suggest that therapeutic strategies after SCI can be directed into two broad modalities: 1) prevention or amelioration of the secondary injury, and 2) restorative or regenerative interventions. Intraspinal transplants have been used after SCI as a means for restoring the severed neuraxis. Fetal cell transplants and, more recently, progenitor cells have been used to restore intraspinal circuitry or to serve as relay for damaged axons. In an attempt to remyelinate anatomically preserved but physiologically disrupted axons, newer therapeutic interventions have incorporated the transplantation of myelinating cells, such as Schwann cells, oligodendrocytes, and olfactory ensheathing cells. Of these cells, the olfactory ensheathing cells have become a more favorable candidate for extensive remyelination and axonal regeneration. Olfactory ensheathing cells are found along the full length of the olfactory nerve, from the basal lamina of the epithelium to the olfactory bulb, crossing the peripheral nervous system-central nervous system junction. In vitro, these cells promote robust axonal growth, in part through cell adhesion molecules and possibly by secretion of neurotrophic growth factors that support axonal elongation and extension. In animal models of SCI, transplantation of ensheathing cells supports axonal remyelination and extensive migration throughout the length of the spinal cord. Although the specific properties of these cells that govern enhanced axon regeneration remain to be elucidated, it seems certain that they will contribute to the establishment of new horizons in SCI research.

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20

Li, Ying, Yves Sauvé, Daqing Li, Raymond D. Lund, and Geoffrey Raisman. "Transplanted Olfactory Ensheathing Cells Promote Regeneration of Cut Adult Rat Optic Nerve Axons." Journal of Neuroscience 23, no. 21 (August 27, 2003): 7783–88. http://dx.doi.org/10.1523/jneurosci.23-21-07783.2003.

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21

Andrews, Peter J., Anne-Lise Poirrier, Valerie J. Lund, and David Choi. "Safety of human olfactory mucosal biopsy for the purpose of olfactory ensheathing cell harvest and nerve repair: a prospective controlled study in patients undergoing endoscopic sinus surgery." Rhinology journal 54, no. 2 (June 1, 2016): 183–91. http://dx.doi.org/10.4193/rhino15.365.

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Background: Nasal olfactory mucosa is an accessible source of olfactory ensheathing cells for spinal cord regeneration. However, safety of the biopsy technique and the effects on sense of smell and nasal function have not been robustly assessed in the form of a prospective controlled study. Methodology: National Health Service ethical approval was granted for this study of 131 patients. The primary outcome measure was olfactory function and the secondary outcomes included postoperative complication rates as well as the SNOT 22, NOSE scale scores and surgeon reported (Lund-Kennedy score) nasal function outcomes. Results: 65 patients underwent functional endoscopic sinus surgery (FESS) and superior turbinate biopsy, and 66 patients underwent FESS only as the control group. There was no significant difference in complication rates between the two groups. All Olfactory function outcomes were unaffected following olfactory biopsy. We demonstrated that the patients quality of life and nasal patency as well as surgeon reported outcome measurements remain unaffected following olfactory harvesting. Conclusions: We have uniquely provided level 2a evidence for the safety of endoscopic biopsy of olfactory mucosa, which does not affect nasal function or the sense of smell compared to standard FESS without biopsy.

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22

Starcevic, Susan L., and Barbara S. Zielinski. "Glutathione and GlutathioneS-Transferase in the Rainbow Trout Olfactory Mucosa during Retrograde Degeneration and Regeneration of the Olfactory Nerve." Experimental Neurology 146, no. 2 (August 1997): 331–40. http://dx.doi.org/10.1006/exnr.1997.6548.

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23

Struble, R. G., and S. Beckman-Randall. "CHONDROITIN SULFATE PROTEOGLYCAN (CSPG) EXPRESSION DURING CENTRAL DEGENERATION AND REGENERATION OF THE OLFACTORY NERVE." Journal of Neuropathology and Experimental Neurology 58, no. 5 (May 1999): 550. http://dx.doi.org/10.1097/00005072-199905000-00174.

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24

Reshamwala, Ronak, Megha Shah, James St John, and Jenny Ekberg. "Survival and Integration of Transplanted Olfactory Ensheathing Cells are Crucial for Spinal Cord Injury Repair: Insights from the Last 10 Years of Animal Model Studies." Cell Transplantation 28, no. 1_suppl (November 15, 2019): 132S—159S. http://dx.doi.org/10.1177/0963689719883823.

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Olfactory ensheathing cells (OECs), the glial cells of the primary olfactory nervous system, support the natural regeneration of the olfactory nerve that occurs throughout life. OECs thus exhibit unique properties supporting neuronal survival and growth. Transplantation of OECs is emerging as a promising treatment for spinal cord injury; however, outcomes in both animals and humans are variable and the method needs improvement and standardization. A major reason for the discrepancy in functional outcomes is the variability in survival and integration of the transplanted cells, key factors for successful spinal cord regeneration. Here, we review the outcomes of OEC transplantation in rodent models over the last 10 years, with a focus on survival and integration of the transplanted cells. We identify the key factors influencing OEC survival: injury type, source of transplanted cells, co-transplantation with other cell types, number and concentration of cells, method of delivery, and time of transplantation after the injury. We found that two key issues are hampering optimization and standardization of OEC transplantation: lack of (1) reliable methods for identifying transplanted cells, and (2) three-dimensional systems for OEC delivery. To develop OEC transplantation as a successful and standardized therapy for spinal cord injury, we must address these issues and increase our understanding of the complex parameters influencing OEC survival.

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25

Eward, William C., Carter Lipton, Jonathan Barnwell, Thomas L. Smith, Matthew Crowe, and L. Andrew Koman. "Nerve Conduit Enhancement with Vomeronasal Organ Improves Rat Sciatic Functional Index in a Segmental Nerve Defect Model." Duke Orthopaedic Journal 1, no. 1 (2011): 9–15. http://dx.doi.org/10.5005/jp-journals-10017-1002.

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ABSTRACT Background Segmental nerve loss presents a challenge to the reconstructive surgeon. The best regenerative results are obtained by using autologous interpositional nerve grafts. While this method can be successful, it necessitates a second surgical step, sacrifices donor nerve function and depends upon a finite supply of potential donor nerves. Collagen nerve conduits are commercially available for reconstruction of segmental nerve defects. However, no conduit-based reconstructive strategy has been as successful as autograft reconstruction. We hypothesized that collagen nerve conduits used to bridge a sciatic nerve defect may be enhanced by grafting with vomeronasal organ (VNO), owing to the unique capacity for regeneration of this mammalian olfactory tissue. Methods 21 rats underwent resection of a 1.0 cm segment of sciatic nerve. Seven rats underwent repair of the resultant nerve defect using a commercially available collagen nerve conduit (NeuraGen, Integra Life Sciences, Plainsboro NJ, USA). Seven rats underwent immediate repair of the nerve defect using the conduit filled with freshly harvested VNO allograft. An additional Seven rats underwent resection of a 4 mm segment of sciatic nerve and direct epineural repair. At 14 weeks postoperatively, all animals underwent walking track analysis. Toe prints were analyzed morphometrically to permit calculation of sciatic functional index (SFI). At 16 weeks postoperatively, rats were sacrificed and tissues were processed for histomorphometric analysis. This analysis included quantification of the number and diameter of myelinated axons as well as calculation of the axon density. Results All animals survived treatment without any serious surgical complications. All sciatic nerves were in continuity at sacrifice. All animals showed signs of sciatic denervation (decubitus ulcers, muscle atrophy) postoperatively. At 14 weeks, the mean sciatic functional index (SFI) was significantly higher in the VNO-enhanced group (p = 0.006) and the epineural repair (ER) groups (p = 0.004) than the conduit-only (CO) group. SFI was equivalent between VNO and ER groups (p = 0.338). Axon density was greater in the VNO (p = 0.013) and ER groups (p = 0.048) than in the CO group. Axon density was equivalent between the VNO and ER groups (p = 0.306). Conclusions In a rat sciatic nerve segmental defect model, modification of collagen nerve conduits to contain the pluripotent neuroepitheilial tissue vomeronasal organ (VNO) improves functional recovery and offers increased axon density relative to reconstruction with an empty conduit (CO).

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Struble, Robert G., David N. Dhanraj, Yun Mei, Marty Wilson, Ruilyn Wang, and Vickram Ramkumar. "β-Amyloid precursor protein-like immunoreactivity is upregulated during olfactory nerve regeneration in adult rats." Brain Research 780, no. 1 (January 1998): 129–37. http://dx.doi.org/10.1016/s0006-8993(97)01187-6.

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27

Esaki, Shinichi, Sachiyo Katsumi, Yuki Hamajima, Yoshihisa Nakamura, and Shingo Murakami. "Transplantation of Olfactory Stem Cells with Biodegradable Hydrogel Accelerates Facial Nerve Regeneration After Crush Injury." STEM CELLS Translational Medicine 8, no. 2 (November 12, 2018): 169–78. http://dx.doi.org/10.1002/sctm.15-0399.

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28

Zhu, Shu, Jun Ge, Yuqing Wang, Fengyu Qi, Teng Ma, Meng Wang, Yafeng Yang, Zhongyang Liu, Jinghui Huang, and Zhuojing Luo. "A synthetic oxygen carrier-olfactory ensheathing cell composition system for the promotion of sciatic nerve regeneration." Biomaterials 35, no. 5 (February 2014): 1450–61. http://dx.doi.org/10.1016/j.biomaterials.2013.10.071.

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29

Boecker, Arne Hendrik, Ahmet Bozkurt, Bong Sung Kim, Haktan Altinova, Julian Tank, Ronald Deumens, Rene Tolba, et al. "Cell-enrichment with olfactory ensheathing cells has limited local extra beneficial effects on nerve regeneration supported by the nerve guide Perimaix." Journal of Tissue Engineering and Regenerative Medicine 12, no. 11 (September 12, 2018): 2125–37. http://dx.doi.org/10.1002/term.2731.

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30

Liadi, Modinat, Andrew Collins, Ying Li, and Daqing Li. "The Impact of Tissue Storage Conditions on Rat Olfactory Ensheathing Cell Yield and the Future Clinical Implications." Cell Transplantation 27, no. 9 (August 10, 2018): 1320–27. http://dx.doi.org/10.1177/0963689718787762.

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Trauma causes spinal cord injury, and the devastating consequences of the injury are due to the failure of the damaged central nervous system (CNS) axons to regenerate. Previous studies have shown that olfactory ensheathing cells (OECs) are a unique type of glial cell and they can promote regeneration of CNS axons to aid recovery after spinal cord injury. Transplantation of OECs, in particular from the olfactory bulb (OB), is considered one of the most promising therapeutic strategies for the repair of CNS injuries, including spinal cord injury. Transplantation of OECs can be autologous or allogenic. Here we focused on the less invasive and more error-proof allograft approach which needs a collection of donor OB tissue for OEC production. In this study, we investigated the effects on the yield and proportions of OECs and olfactory nerve fibroblasts (ONFs) from storing OB tissue in various media for periods of 24 and 48 hours. The OEC yield contributes to the viability of a successful cell transplant. We concluded that storing OB tissue for a period longer than 24 hours negatively impacted the total cell number and subsequently the OEC population. This study provides useful information for future clinical applications.

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31

Yan, Carol H., Aakanksha Rathor, Kaelyn Krook, Yifei Ma, Melissa R. Rotella, Robert L. Dodd, Peter H. Hwang, et al. "Effect of Omega-3 Supplementation in Patients With Smell Dysfunction Following Endoscopic Sellar and Parasellar Tumor Resection: A Multicenter Prospective Randomized Controlled Trial." Neurosurgery 87, no. 2 (January 17, 2020): E91—E98. http://dx.doi.org/10.1093/neuros/nyz559.

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Abstract BACKGROUND Endoscopic endonasal approaches pose the potential risk of olfactory loss. Loss of olfaction and potentially taste can be permanent and greatly affect patients’ quality of life. Treatments for olfactory loss have had limited success. Omega-3 supplementation may be a therapeutic option with its effect on wound healing and nerve regeneration. OBJECTIVE To evaluate the impact on olfaction in patients treated with omega-3 supplementation following endoscopic skull base tumor resection. METHODS In this multi-institutional, prospective, randomized controlled trial, 110 patients with sellar or parasellar tumors undergoing endoscopic resection were randomized to nasal saline irrigations or nasal saline irrigations plus omega-3 supplementation. The University of Pennsylvania Smell Identification Test (UPSIT) was administered preoperatively and at 6 wk, 3 mo, and 6 mo postoperatively. RESULTS Eighty-seven patients completed all 6 mo of follow-up (41 control arm, 46 omega-3 arm). At 6 wk postoperatively, 25% of patients in both groups experienced a clinically significant loss in olfaction. At 3 and 6 mo, patients receiving omega-3 demonstrated significantly less persistent olfactory loss compared to patients without supplementation (P = .02 and P = .01, respectively). After controlling for multiple confounding variables, omega-3 supplementation was found to be protective against olfactory loss (odds ratio [OR] 0.05, 95% CI 0.003-0.81, P = .03). Tumor functionality was a significant independent predictor for olfactory loss (OR 32.7, 95% CI 1.15-929.5, P = .04). CONCLUSION Omega-3 supplementation appears to be protective for the olfactory system during the healing period in patients who undergo endoscopic resection of sellar and parasellar masses.

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Radtke, Christine, and Jeffery D. Kocsis. "Peripheral Nerve Injuries and Transplantation of Olfactory Ensheathing Cells for Axonal Regeneration and Remyelination: Fact or Fiction?" International Journal of Molecular Sciences 13, no. 12 (October 10, 2012): 12911–24. http://dx.doi.org/10.3390/ijms131012911.

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Guérout, Nicolas, Célia Duclos, Laurent Drouot, Olivia Abramovici, Nicolas Bon-Mardion, Yann Lacoume, Laetitia Jean, Olivier Boyer, and Jean-Paul Marie. "Transplantation of olfactory ensheathing cells promotes axonal regeneration and functional recovery of peripheral nerve lesion in rats." Muscle & Nerve 43, no. 4 (February 8, 2011): 543–51. http://dx.doi.org/10.1002/mus.21907.

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Paviot, Alexandre, Nicolas Bon-Mardion, Célia Duclos, Jean-Paul Marie, and Nicolas Guérout. "Although olfactory ensheathing cells have remarkable potential to sustain nerve regeneration, they cannot be applied to a severe vagus nerve section/resection model." Muscle & Nerve 43, no. 6 (May 23, 2011): 919–20. http://dx.doi.org/10.1002/mus.22044.

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Li, Chao, Mei Shi, Yang Zhang, Wen-Tao Wang, and Chun-Rong Gong. "Combination of olfactory ensheathing cells and human umbilical cord mesenchymal stem cell-derived exosomes promotes sciatic nerve regeneration." Neural Regeneration Research 15, no. 10 (2020): 1903. http://dx.doi.org/10.4103/1673-5374.280330.

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Astic, L., V. Pellier-Monnin, D. Saucier, C. Charrier, and P. Mehlen. "Expression of netrin-1 and netrin-1 receptor, DCC, in the rat olfactory nerve pathway during development and axonal regeneration." Neuroscience 109, no. 4 (February 2002): 643–56. http://dx.doi.org/10.1016/s0306-4522(01)00535-8.

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Gong, Qizhi, Mary S. Bailey, Sarah K. Pixley, Matthew Ennis, W. Liu, and Michael T. Shipley. "Localization and regulation of low affinity nerve growth factor receptor expression in the rat olfactory system during development and regeneration." Journal of Comparative Neurology 344, no. 3 (June 15, 1994): 336–48. http://dx.doi.org/10.1002/cne.903440303.

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Martín-López, Eduardo, Manuel Nieto-Díaz, and Manuel Nieto-Sampedro. "Differential Adhesiveness and Neurite-promoting Activity for Neural Cells of Chitosan, Gelatin, and Poly-l-Lysine Films." Journal of Biomaterials Applications 26, no. 7 (September 28, 2010): 791–809. http://dx.doi.org/10.1177/0885328210379928.

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Chitosan (Ch) and some of its derivatives have been proposed as good biomaterials for tissue engineering, to construct scaffolds promoting tissue regeneration. In this work we made composite films from Ch and mixtures of Ch with gelatin (G) and poly-l-lysine (PLL), and evaluated the growth on these films of PC12 and C6 lines as well as neurons and glial cells derived from cerebral tissue and dorsal root ganglia (DRG). C6 glioma cells proliferated on Ch, G, and Ch + G films, although metabolic activity was decreased by the presence of the G in the mixtures. NGF-differentiated PC12 cells, adhered preferentially on Ch and films containing PLL. Unlike NGF-treated PC12 cells, cortical and hippocampal neurons showed good adhesion to Ch and Ch + G films, where they extended neurites. Astrocytes adhered on Ch, Ch + G, and Ch + PLL mixtures, although viability decreased during the culture time. Olfactory ensheathing cells (OEC) adhered and proliferated to confluency on the wells covered with Ch + G films. Neurites from DRGs exhibited high extension on these films. These results demonstrate that Ch + G films have excellent adhesive properties for both neurons and regeneration-promoting glia (OEC). These films also promoted neurite extension from DRG, making them good candidates for tissue engineering of nerve repair.

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Karimi, Sarah, Zohreh Bagher, Najmeh Najmoddin, Sara Simorgh, and Mohamad Pezeshki-Modaress. "Alginate-magnetic short nanofibers 3D composite hydrogel enhances the encapsulated human olfactory mucosa stem cells bioactivity for potential nerve regeneration application." International Journal of Biological Macromolecules 167 (January 2021): 796–806. http://dx.doi.org/10.1016/j.ijbiomac.2020.11.199.

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Blits, Bas, Gerard J. Boer, and Joost Verhaagen. "Pharmacological, Cell, and Gene Therapy Strategies to Promote Spinal Cord Regeneration." Cell Transplantation 11, no. 6 (September 2002): 593–613. http://dx.doi.org/10.3727/000000002783985521.

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In this review, recent studies using pharmacological treatment, cell transplantation, and gene therapy to promote regeneration of the injured spinal cord in animal models will be summarized. Pharmacological and cell transplantation treatments generally revealed some degree of effect on the regeneration of the injured ascending and descending tracts, but further improvements to achieve a more significant functional recovery are necessary. The use of gene therapy to promote repair of the injured nervous system is a relatively new concept. It is based on the development of methods for delivering therapeutic genes to neurons, glia cells, or nonneural cells. Direct in vivo gene transfer or gene transfer in combination with (neuro)transplantation (ex vivo gene transfer) appeared powerful strategies to promote neuronal survival and axonal regrowth following traumatic injury to the central nervous system. Recent advances in understanding the cellular and molecular mechanisms that govern neuronal survival and neurite outgrowth have enabled the design of experiments aimed at viral vector-mediated transfer of genes encoding neurotrophic factors, growth-associated proteins, cell adhesion molecules, and antiapoptotic genes. Central to the success of these approaches was the development of efficient, nontoxic vectors for gene delivery and the acquirement of the appropriate (genetically modified) cells for neurotransplantation. Direct gene transfer in the nervous system was first achieved with herpes viral and E1-deleted adenoviral vectors. Both vector systems are problematic in that these vectors elicit immunogenic and cytotoxic responses. Adeno-associated viral vectors and lentiviral vectors constitute improved gene delivery systems and are beginning to be applied in neuroregeneration research of the spinal cord. Ex vivo approaches were initially based on the implantation of genetically modified fibroblasts. More recently, transduced Schwann cells, genetically modified pieces of peripheral nerve, and olfactory ensheathing glia have been used as implants into the injured spinal cord.

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Pascal, Davide, Alessia Giovannelli, Sara Gnavi, Stefan Adriaan Hoyng, Fred de Winter, Michela Morano, Federica Fregnan, et al. "Characterization of Glial Cell Models andIn VitroManipulation of the Neuregulin1/ErbB System." BioMed Research International 2014 (2014): 1–15. http://dx.doi.org/10.1155/2014/310215.

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The neuregulin1/ErbB system plays an important role in Schwann cell behavior both in normal and pathological conditions. Upon investigation of the expression of the neuregulin1/ErbB systemin vitro, we explored the possibility to manipulate the system in order to increase the migration of Schwann cells, that play a fundamental role in the peripheral nerve regeneration. Comparison of primary cells and stable cell lines shows that both primary olfactory bulb ensheathing cells and a corresponding cell line express ErbB1-ErbB2 and neuregulin1, and that both primary Schwann cells and a corresponding cell line express ErbB2-ErbB3, while only primary Schwann cells express neuregulin1. To interfere with the neuregulin1/ErbB system, the soluble extracellular domain of the neuregulin1 receptor ErbB4 (ecto-ErbB4) was expressedin vitroin the neuregulin1 expressing cell line, and an unexpected increase in cell motility was observed.In vitroexperiments suggest that the back signaling mediated by the transmembrane neuregulin1 plays a role in the migratory activity induced by ecto-ErbB4. These results indicate that ecto-ErbB4 could be usedin vivoas a tool to manipulate the neuregulin1/ErbB system.

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Tabakow, Pawel, Geoffrey Raisman, Wojciech Fortuna, Marcin Czyz, Juliusz Huber, Daqing Li, Pawel Szewczyk, et al. "Functional Regeneration of Supraspinal Connections in a Patient with Transected Spinal Cord following Transplantation of Bulbar Olfactory Ensheathing Cells with Peripheral Nerve Bridging." Cell Transplantation 23, no. 12 (December 2014): 1631–55. http://dx.doi.org/10.3727/096368914x685131.

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Guest, James, and W. Dalton Dietrich. "Commentary Regarding the Recent Publication by Tabakow et al., “Functional Regeneration of Supraspinal Connections in a Patient with Transected Spinal Cord following Transplantation of Bulbar Olfactory Ensheathing Cells with Peripheral Nerve Bridging”." Journal of Neurotrauma 32, no. 15 (August 2015): 1176–78. http://dx.doi.org/10.1089/neu.2014.3790.

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Hanemann, C. O., G. Kuhn, A. Lie, C. Gillen, F. Bosse, P. Spreyer, and H. W. Müller. "Expression of decorin mRNA in the nervous system of rat." Journal of Histochemistry & Cytochemistry 41, no. 9 (September 1993): 1383–91. http://dx.doi.org/10.1177/41.9.8354878.

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A rat cDNA clone (pCD67) isolated from a cDNA library of regenerating sciatic nerve by differential hybridization screening revealed 75% homology on the nucleic acid level and 81% homology (including conservative amino acid changes) to the deduced amino acid sequence of the core protein of human dermatan/chondroitin sulfate proteoglycan decorin (PGII, PG40, PG-S2). Two transcripts of 1.3 and 1.75 KB very similar in size to the two decorin mRNA species previously identified in connective tissue were detected by Northern blotting in both normal and injured sciatic nerve and in the mature and embryonic rat brain. The steady-state level of the decorin 1.3 KB mRNA was very much higher in peripheral nerve than in the central nervous system or in other non-neural tissues (skeletal muscle, heart, colon, kidney). In situ hybridization experiments indicated that decorin mRNA is expressed by Schwann cells and vascular cells in peripheral nerve. In the spinal cord the ventral horn motor neurons and other neurons in gray matter showed specific hybridization signals. Furthermore, in situ hybridization indicated decorin expression in Purkinje neurons and cells of the molecular layer in cerebellum, and in neurons of the primary olfactory cortex and brainstem (pons). Our data clearly demonstrate decorin mRNA expression in distinct neural cell populations, suggesting yet unknown functions of this proteoglycan in the peripheral and central nervous system.

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Zheng, Rui, Zhong-Hao Zhang, Yu-Xi Zhao, Chen Chen, Shi-Zheng Jia, Xian-Chun Cao, Li-Ming Shen, Jia-Zuan Ni, and Guo-Li Song. "Transcriptomic Insights into the Response of the Olfactory Bulb to Selenium Treatment in a Mouse Model of Alzheimer’s Disease." International Journal of Molecular Sciences 20, no. 12 (June 19, 2019): 2998. http://dx.doi.org/10.3390/ijms20122998.

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Alzheimer’s disease (AD) is a devastating neurodegenerative disorder characterized by the presence of extracellular senile plaques primarily composed of Aβ peptides and intracellular neurofibrillary tangles (NFTs) composed of hyperphosphorylated tau proteins. Olfactory dysfunction is an early clinical phenotype in AD and was reported to be attributable to the presence of NFTs, senile Aβ plaques in the olfactory bulb (OB). Our previous research found that selenomethionine (Se-Met), a major form of selenium (Se) in organisms, effectively increased oxidation resistance as well as reduced the generation and deposition of Aβ and tau hyperphosphorylation in the olfactory bulb of a triple transgenic mouse model of AD (3×Tg-AD), thereby suggesting a potential therapeutic option for AD. In this study, we further investigated changes in the transcriptome data of olfactory bulb tissues of 7-month-old triple transgenic AD (3×Tg-AD) mice treated with Se-Met (6 µg/mL) for three months. Comparison of the gene expression profile between Se-Met-treated and control mice revealed 143 differentially expressed genes (DEGs). Among these genes, 21 DEGs were upregulated and 122 downregulated. The DEGs were then annotated against the Gene Ontology (GO) and Kyoto Encyclopedia of Genes and Genomes (KEGG) databases. The results show that upregulated genes can be roughly classified into three types. Some of them mainly regulate the regeneration of nerves, such as Fabp7, Evt5 and Gal; some are involved in improving cognition and memory, such as Areg; and some are involved in anti-oxidative stress and anti-apoptosis, such as Adcyap1 and Scg2. The downregulated genes are mainly associated with inflammation and apoptosis, such as Lrg1, Scgb3a1 and Pglyrp1. The reliability of the transcriptomic data was validated by quantitative real time polymerase chain reaction (qRT-PCR) for the selected genes. These results were in line with our previous study, which indicated therapeutic effects of Se-Met on AD mice, providing a theoretical basis for further study of the treatment of AD by Se-Met.

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Sandvig, Ioanna, Marte Thuen, Linh Hoang, Øystein Olsen, Thomas CP Sardella, Christian Brekken, Kåre E. Tvedt, et al. "In vivo MRI of olfactory ensheathing cell grafts and regenerating axons in transplant mediated repair of the adult rat optic nerve." NMR in Biomedicine 25, no. 4 (August 26, 2011): 620–31. http://dx.doi.org/10.1002/nbm.1778.

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Barton, Matthew, James John, Mary Clarke, Alison Wright, and Jenny Ekberg. "The Glia Response after Peripheral Nerve Injury: A Comparison between Schwann Cells and Olfactory Ensheathing Cells and Their Uses for Neural Regenerative Therapies." International Journal of Molecular Sciences 18, no. 2 (January 29, 2017): 287. http://dx.doi.org/10.3390/ijms18020287.

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Bicker, Gerd, and Michael Stern. "Structural and Functional Plasticity in the Regenerating Olfactory System of the Migratory Locust." Frontiers in Physiology 11 (December 3, 2020). http://dx.doi.org/10.3389/fphys.2020.608661.

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Regeneration after injury is accompanied by transient and lasting changes in the neuroarchitecture of the nervous system and, thus, a form of structural plasticity. In this review, we introduce the olfactory pathway of a particular insect as a convenient model to visualize neural regeneration at an anatomical level and study functional recovery at an electrophysiological level. The olfactory pathway of the locust (Locusta migratoria) is characterized by a multiglomerular innervation of the antennal lobe by olfactory receptor neurons. These olfactory afferents were axotomized by crushing the base of the antenna. The resulting degeneration and regeneration in the antennal lobe could be quantified by size measurements, dye labeling, and immunofluorescence staining of cell surface proteins implicated in axonal guidance during development. Within 3 days post lesion, the antennal lobe volume was reduced by 30% and from then onward regained size back to normal by 2 weeks post injury. The majority of regenerating olfactory receptor axons reinnervated the glomeruli of the antennal lobe. A few regenerating axons project erroneously into the mushroom body on a pathway that is normally chosen by second-order projection neurons. Based on intracellular responses of antennal lobe output neurons to odor stimulation, regenerated fibers establish functional synapses again. Following complete absence after nerve crush, responses to odor stimuli return to control level within 10–14 days. On average, regeneration of afferents, and re-established synaptic connections appear faster in younger fifth instar nymphs than in adults. The initial degeneration of olfactory receptor axons has a trans-synaptic effect on a second order brain center, leading to a transient size reduction of the mushroom body calyx. Odor-evoked oscillating field potentials, absent after nerve crush, were restored in the calyx, indicative of regenerative processes in the network architecture. We conclude that axonal regeneration in the locust olfactory system appears to be possible, precise, and fast, opening an avenue for future mechanistic studies. As a perspective of biomedical importance, the current evidence for nitric oxide/cGMP signaling as positive regulator of axon regeneration in connectives of the ventral nerve cord is considered in light of particular regeneration studies in vertebrate central nervous systems.

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Nazareth, Lynn, James St John, Mariyam Murtaza, and Jenny Ekberg. "Phagocytosis by Peripheral Glia: Importance for Nervous System Functions and Implications in Injury and Disease." Frontiers in Cell and Developmental Biology 9 (April 8, 2021). http://dx.doi.org/10.3389/fcell.2021.660259.

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The central nervous system (CNS) has very limited capacity to regenerate after traumatic injury or disease. In contrast, the peripheral nervous system (PNS) has far greater capacity for regeneration. This difference can be partly attributed to variances in glial-mediated functions, such as axon guidance, structural support, secretion of growth factors and phagocytic activity. Due to their growth-promoting characteristic, transplantation of PNS glia has been trialed for neural repair. After peripheral nerve injuries, Schwann cells (SCs, the main PNS glia) phagocytose myelin debris and attract macrophages to the injury site to aid in debris clearance. One peripheral nerve, the olfactory nerve, is unique in that it continuously regenerates throughout life. The olfactory nerve glia, olfactory ensheathing cells (OECs), are the primary phagocytes within this nerve, continuously clearing axonal debris arising from the normal regeneration of the nerve and after injury. In contrast to SCs, OECs do not appear to attract macrophages. SCs and OECs also respond to and phagocytose bacteria, a function likely critical for tackling microbial invasion of the CNS via peripheral nerves. However, phagocytosis is not always effective; inflammation, aging and/or genetic factors may contribute to compromised phagocytic activity. Here, we highlight the diverse roles of SCs and OECs with the focus on their phagocytic activity under physiological and pathological conditions. We also explore why understanding the contribution of peripheral glia phagocytosis may provide us with translational strategies for achieving axonal regeneration of the injured nervous system and potentially for the treatment of certain neurological diseases.

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Saïd, Zaer, Charnavel Pauline, Batut Claire, Duclos Celia, Marie Jean-Paul, and Bon-Mardion Nicolas. "Olfactory Ecto-Mesenchymal Stem Cells in Laryngeal Nerve Regeneration in Rats." Journal of Voice, November 2019. http://dx.doi.org/10.1016/j.jvoice.2019.10.012.

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