Academic literature on the topic 'Axonal loss'
Create a spot-on reference in APA, MLA, Chicago, Harvard, and other styles
Consult the lists of relevant articles, books, theses, conference reports, and other scholarly sources on the topic 'Axonal loss.'
Next to every source in the list of references, there is an 'Add to bibliography' button. Press on it, and we will generate automatically the bibliographic reference to the chosen work in the citation style you need: APA, MLA, Harvard, Chicago, Vancouver, etc.
You can also download the full text of the academic publication as pdf and read online its abstract whenever available in the metadata.
Journal articles on the topic "Axonal loss"
1
Spinner, Michael A., Katherine Pinter, Catherine M. Drerup, and Tory G. Herman. "A Conserved Role for Vezatin Proteins in Cargo-Specific Regulation of Retrograde Axonal Transport." Genetics 216, no. 2 (August 11, 2020): 431–45. http://dx.doi.org/10.1534/genetics.120.303499.
Full textAbstract:
Active transport of organelles within axons is critical for neuronal health. Retrograde axonal transport, in particular, relays neurotrophic signals received by axon terminals to the nucleus and circulates new material among en passant synapses. A single motor protein complex, cytoplasmic dynein, is responsible for nearly all retrograde transport within axons: its linkage to and transport of diverse cargos is achieved by cargo-specific regulators. Here, we identify Vezatin as a conserved regulator of retrograde axonal transport. Vertebrate Vezatin (Vezt) is required for the maturation and maintenance of cell-cell junctions and has not previously been implicated in axonal transport. However, a related fungal protein, VezA, has been shown to regulate retrograde transport of endosomes in hyphae. In a forward genetic screen, we identified a loss-of-function mutation in the Drosophila vezatin-like (vezl) gene. We here show that vezl loss prevents a subset of endosomes, including signaling endosomes containing activated BMP receptors, from initiating transport out of motor neuron terminal boutons. vezl loss also decreases the transport of endosomes and dense core vesicles, but not mitochondria, within axon shafts. We disrupted vezt in zebrafish and found that vezt loss specifically impairs the retrograde axonal transport of late endosomes, causing their accumulation in axon terminals. Our work establishes a conserved, cargo-specific role for Vezatin proteins in retrograde axonal transport.
2
Minzenberg, Michael, Michelle Berkelaar, Garth Bray, and Lisa Mckerracher. "Changes in retinal ganglion cell axons after optic nerve crush: neurofilament expression is not the sole determinant of calibre." Biochemistry and Cell Biology 73, no. 9-10 (September 1, 1995): 599–604. http://dx.doi.org/10.1139/o95-065.
Full textAbstract:
After injury in the central nervous system of adult mammals, many of the axons that remain attached to their intact cell bodies degenerate and decrease in calibre. To understand this process better, we have investigated the relationship between axonal loss, cell loss, and the time course of changes in axonal calibre. Optic nerves (ONs) were crushed and the numbers and sizes of axons remaining close to the cell bodies (2 mm from the eye) and near the site of the lesion (6 mm from the eye) were determined for nerves examined between 1 week and 3 months after injury. Comparison with the retinal ganglion cell (RGC) counts from the same animals revealed that axonal loss was concomitant with cell body loss for at least the first 2 weeks after injury. However, there was no significant change in the calibre of the surviving neurons until 1 month after injury. Thereafter, the axonal calibre was decreased equally along the ON. No progressive somatofugal atrophy was observed. These decreases in axonal calibre occur much later than the immediate drop in neurofilament (NF) expression that also follows injury. The late effect of injury on axonal calibre suggests that NF expression is not the sole determinant of axon size of the RGC fibers in the ON. Other factors are likely additional contributing factors, such as the decreased rate of axonal transport that would help maintain the axonal neurofilament content.Key words: axonal calibre, axotomy, neuronal cell death, neurofilaments, retinal ganglion cell, optic nerve.
3
Zheng, Yanrong, Xiangnan Zhang, Xiaoli Wu, Lei Jiang, Anil Ahsan, Shijia Ma, Ziyu Xiao, et al. "Somatic autophagy of axonal mitochondria in ischemic neurons." Journal of Cell Biology 218, no. 6 (April 12, 2019): 1891–907. http://dx.doi.org/10.1083/jcb.201804101.
Full textAbstract:
Mitophagy protects against ischemic neuronal injury by eliminating damaged mitochondria, but it is unclear how mitochondria in distal axons are cleared. We find that oxygen and glucose deprivation-reperfusion reduces mitochondrial content in both cell bodies and axons. Axonal mitochondria elimination was not abolished in Atg7fl/fl;nes-Cre neurons, suggesting the absence of direct mitophagy in axons. Instead, axonal mitochondria were enwrapped by autophagosomes in soma and axon-derived mitochondria prioritized for elimination by autophagy. Intriguingly, axonal mitochondria showed prompt loss of anterograde motility but increased retrograde movement upon reperfusion. Anchoring of axonal mitochondria by syntaphilin blocked neuronal mitophagy and aggravated injury. Conversely, induced binding of mitochondria to dynein reinforced retrograde transport and enhanced mitophagy to prevent mitochondrial dysfunction and attenuate neuronal injury. Therefore, we reveal somatic autophagy of axonal mitochondria in ischemic neurons and establish a direct link of retrograde mitochondrial movement with mitophagy. Our findings may provide a new concept for reducing ischemic neuronal injury by correcting mitochondrial motility.
4
Rao, Mala V., Megan K. Houseweart, Toni L. Williamson, Thomas O. Crawford, Janet Folmer, and Don W. Cleveland. "Neurofilament-dependent Radial Growth of Motor Axons and Axonal Organization of Neurofilaments Does Not Require the Neurofilament Heavy Subunit (NF-H) or Its Phosphorylation." Journal of Cell Biology 143, no. 1 (October 5, 1998): 171–81. http://dx.doi.org/10.1083/jcb.143.1.171.
Full textAbstract:
Neurofilaments are essential for establishment and maintenance of axonal diameter of large myelinated axons, a property that determines the velocity of electrical signal conduction. One prominent model for how neurofilaments specify axonal growth is that the 660–amino acid, heavily phosphorylated tail domain of neurofilament heavy subunit (NF-H) is responsible for neurofilament-dependent structuring of axoplasm through intra-axonal crossbridging between adjacent neurofilaments or to other axonal structures. To test such a role, homologous recombination was used to generate NF-H–null mice. In peripheral motor and sensory axons, absence of NF-H does not significantly affect the number of neurofilaments or axonal elongation or targeting, but it does affect the efficiency of survival of motor and sensory axons. Loss of NF-H caused only a slight reduction in nearest neighbor spacing of neurofilaments and did not affect neurofilament distribution in either large- or small-diameter motor axons. Since postnatal growth of motor axon caliber continues largely unabated in the absence of NF-H, neither interactions mediated by NF-H nor the extensive phosphorylation of it within myelinated axonal segments are essential features of this growth.
5
Haney, C. A., Z. Sahenk, C. Li, V. P. Lemmon, J. Roder, and B. D. Trapp. "Heterophilic Binding of L1 on Unmyelinated Sensory Axons Mediates Schwann Cell Adhesion and Is Required for Axonal Survival." Journal of Cell Biology 146, no. 5 (September 6, 1999): 1173–84. http://dx.doi.org/10.1083/jcb.146.5.1173.
Full textAbstract:
This study investigated the function of the adhesion molecule L1 in unmyelinated fibers of the peripheral nervous system (PNS) by analysis of L1- deficient mice. We demonstrate that L1 is present on axons and Schwann cells of sensory unmyelinated fibers, but only on Schwann cells of sympathetic unmyelinated fibers. In L1-deficient sensory nerves, Schwann cells formed but failed to retain normal axonal ensheathment. L1-deficient mice had reduced sensory function and loss of unmyelinated axons, while sympathetic unmyelinated axons appeared normal. In nerve transplant studies, loss of axonal-L1, but not Schwann cell-L1, reproduced the L1-deficient phenotype. These data establish that heterophilic axonal-L1 interactions mediate adhesion between unmyelinated sensory axons and Schwann cells, stabilize the polarization of Schwann cell surface membranes, and mediate a trophic effect that assures axonal survival.
6
Wisco, Dolora, Eric D. Anderson, Michael C. Chang, Caren Norden, Tatiana Boiko, Heike Fölsch, and Bettina Winckler. "Uncovering multiple axonal targeting pathways in hippocampal neurons." Journal of Cell Biology 162, no. 7 (September 29, 2003): 1317–28. http://dx.doi.org/10.1083/jcb.200307069.
Full textAbstract:
Neuronal polarity is, at least in part, mediated by the differential sorting of membrane proteins to distinct domains, such as axons and somata/dendrites. We investigated the pathways underlying the subcellular targeting of NgCAM, a cell adhesion molecule residing on the axonal plasma membrane. Following transport of NgCAM kinetically, surprisingly we observed a transient appearance of NgCAM on the somatodendritic plasma membrane. Down-regulation of endocytosis resulted in loss of axonal accumulation of NgCAM, indicating that the axonal localization of NgCAM was dependent on endocytosis. Our data suggest the existence of a dendrite-to-axon transcytotic pathway to achieve axonal accumulation. NgCAM mutants with a point mutation in a crucial cytoplasmic tail motif (YRSL) are unable to access the transcytotic route. Instead, they were found to travel to the axon on a direct route. Therefore, our results suggest that multiple distinct pathways operate in hippocampal neurons to achieve axonal accumulation of membrane proteins.
7
Lamoureux, Phillip, Gordon Ruthel, Robert E. Buxbaum, and Steven R. Heidemann. "Mechanical tension can specify axonal fate in hippocampal neurons." Journal of Cell Biology 159, no. 3 (November 4, 2002): 499–508. http://dx.doi.org/10.1083/jcb.200207174.
Full textAbstract:
Here we asked whether applied mechanical tension would stimulate undifferentiated minor processes of cultured hippocampal neurons to become axons and whether tension could induce a second axon in an already polarized neuron. Experimental tension applied to minor processes produced extensions that demonstrated axonal character, regardless of the presence of an existing axon. Towed neurites showed a high rate of spontaneous growth cone advance and could continue to grow out for 1–3 d after towing. The developmental course of experimental neurites was found to be similar to that of unmanipulated spontaneous axons. Furthermore, the experimentally elongated neurites showed compartmentation of the axonal markers dephospho-tau and L-1 in towed outgrowth after 24 h. Extension of a second axon from an already polarized neuron does not lead to the loss of the spontaneous axon either immediately or after longer term growth. In addition, we were able to initiate neurites de novo that subsequently acquired axonal character even though spontaneous growth cone advance began while the towed neurite was still no longer than its sibling processes. This suggests that tension rather than the achievement of a critical neurite length determined axonal specification.
8
Noval, Susana, Inés Contreras, Silvia Muñoz, Celia Oreja-Guevara, Beatriz Manzano, and Gema Rebolleda. "Optical Coherence Tomography in Multiple Sclerosis and Neuromyelitis Optica: An Update." Multiple Sclerosis International 2011 (2011): 1–11. http://dx.doi.org/10.1155/2011/472790.
Full textAbstract:
Optical coherence tomography (OCT) uses light interference patterns to produce a cross-sectional image of the retina. It is capable of measuring the unmyelinated axons of the retinal ganglionar cells as they converge on the optic disc. In a disease like multiple sclerosis (MS), in which axonal loss has been identified as an important cause of sustained disability, it may prove an invaluable tool. OCT has demonstrated that axonal loss occurs after each episode of optic neuritis and that the degree of axonal loss is correlated to visual outcomes. Furthermore, axonal loss occurs in MS even in the absence of inflammatory episodes, and the degree of this loss is correlated with the duration of the disease process, with more thinning as the disease advances and in progressive forms. Thus, OCT retinal nerve fiber layer measurements may represent an objective outcome measure with which to evaluate the effect of treatment.
9
Tallantyre, Emma C., Lars Bø, Omar Al-Rawashdeh, Trudy Owens, Chris H. Polman, James S. Lowe, and Nikos Evangelou. "Clinico-pathological evidence that axonal loss underlies disability in progressive multiple sclerosis." Multiple Sclerosis Journal 16, no. 4 (March 9, 2010): 406–11. http://dx.doi.org/10.1177/1352458510364992.
Full textAbstract:
Growing evidence suggests that axonal degeneration rather than demyelination is the pathological substrate underlying chronic, irreversible disability in multiple sclerosis. However, direct evidence linking clinical disability measured in vivo with corresponding post-mortem measures of axonal pathology is lacking. Our objective in this study was to investigate the relationship between motor disability accumulated by patients with multiple sclerosis during life and the degree of axonal loss observed in their descending motor tracts after death. Human spinal cord derived at autopsy from 45 patients with multiple sclerosis was investigated. The medical records of each patient were reviewed by a multiple sclerosis neurologist to determine the degree of motor disability reached before death. Spinal cord sections were stained immunohistochemically. The degree of demyelination and the number of surviving corticospinal tract axons were measured in each patient. Patients who had accumulated higher levels of motor disability prior to death demonstrated fewer surviving corticospinal axons. Motor disability did not correlate with degree of demyelination. This study provides for the first time, direct clinico-pathological evidence that axonal loss is the pathological substrate of established disability in multiple sclerosis.
10
Llobet Rosell, Arnau, and Lukas J. Neukomm. "Axon death signalling in Wallerian degeneration among species and in disease." Open Biology 9, no. 8 (August 2019): 190118. http://dx.doi.org/10.1098/rsob.190118.
Full textAbstract:
Axon loss is a shared feature of nervous systems being challenged in neurological disease, by chemotherapy or mechanical force. Axons take up the vast majority of the neuronal volume, thus numerous axonal intrinsic and glial extrinsic support mechanisms have evolved to promote lifelong axonal survival. Impaired support leads to axon degeneration, yet underlying intrinsic signalling cascades actively promoting the disassembly of axons remain poorly understood in any context, making the development to attenuate axon degeneration challenging. Wallerian degeneration serves as a simple model to study how axons undergo injury-induced axon degeneration (axon death). Severed axons actively execute their own destruction through an evolutionarily conserved axon death signalling cascade. This pathway is also activated in the absence of injury in diseased and challenged nervous systems. Gaining insights into mechanisms underlying axon death signalling could therefore help to define targets to block axon loss. Herein, we summarize features of axon death at the molecular and subcellular level. Recently identified and characterized mediators of axon death signalling are comprehensively discussed in detail, and commonalities and differences across species highlighted. We conclude with a summary of engaged axon death signalling in humans and animal models of neurological conditions. Thus, gaining mechanistic insights into axon death signalling broadens our understanding beyond a simple injury model. It harbours the potential to define targets for therapeutic intervention in a broad range of human axonopathies.
Dissertations / Theses on the topic "Axonal loss"
1
Evangelou, N. "Approaches to defining axonal loss in multiple sclerosis." Thesis, University of Oxford, 2000. http://ethos.bl.uk/OrderDetails.do?uin=uk.bl.ethos.249538.
Full text
2
Fernando, Francisca Shama. "The role of the slow Wallerian degeneration genes in human neurodegeneration." Thesis, University of Oxford, 2003. http://ethos.bl.uk/OrderDetails.do?uin=uk.bl.ethos.289356.
Full text
3
Young, Elizabeth Ann. "Axonal Na/K ATPase: Localization, Loss, and Lessons Learned." Case Western Reserve University School of Graduate Studies / OhioLINK, 2010. http://rave.ohiolink.edu/etdc/view?acc_num=case1278699912.
Full text
4
Licht-Mayer, Simon. "Mitochondrial dynamics in demyelinated axons in a cerebellar slice culture system." Thesis, University of Edinburgh, 2018. http://hdl.handle.net/1842/33134.
Full textAbstract:
Axonal degeneration is the major cause of disability in progressive multiple sclerosis (MS). It has been shown that in MS and relevant disease models, demyelinated axons harbor an increased number of mitochondria, which is reflected in bigger stationary sites of mitochondria, increased mitochondrial activity and increased transport speed of mitochondria. This axonal response of mitochondria to demyelination (ARMD) is protective, as there is an increase in energy demand due to the redistribution of sodium channels along the axon following demyelination. However, it remains to be determined how this ARMD is mounted and how mitochondrial dynamics are involved. By using in vivo and in vitro systems we are determined to elucidate the transport and fusion dynamics of the ARMD and where these additional mitochondria come from. Using a cerebellar slice culture system with lysolecithin induced demyelination, we show that the increase in mitochondrial occupancy of the axon already occurs at 24 hours after demyelination and plateaus around 3 to 4 days after demyelination. At 24 hours, there was a steep increase in the mitochondrial numbers inside the axon, which is then followed by an increase in mitochondrial size over the following days. All parameters decrease again over the following days, but remain elevated compared to baseline even 12 days after demyelination. To determine the source of these additional mitochondria and to assess the fusion dynamics within the axon, we used a lentivirus expressing a mitochondrial targeted photoconvertible dye (mEOS2) to label mitochondria in Purkinje cells. The mitochondria that are labelled green in the Purkinje cell axons are then photoconverted to red by illuminating the initial part of the axon with a 405-nm laser and imaged over the following 20 minutes to determine the transport and fusion dynamics. This showed an increased number of mitochondria moving from the cell body into the axon, as well as an increase in retrograde transport of mitochondria in the demyelinated compared to the myelinated axons. Furthermore the size of newly transported mitochondria and their speed was increased in the anterograde direction. Furthermore, the fusion rate of newly transported mitochondria with stationary converted mitochondria was increased in the demyelinated axons compared to myelinated control. These changes can also be observed in unmyelinated axons, as well as axons of cerebellar slices of the dysmyelinating shiverer mutant with or without lysolecithin treatment. The manipulation of mitochondrial dynamics after demyelination with the fission inhibitor mdivi-1 and the ATPase inhibitor oligomycin both showed an increasing or decreasing effect on the mitochondrial parameters after demyelination respectively. The effect on the axonal health after demyelination was detrimental with both of these treatments. Increasing mitochondrial biogenesis with pioglitazone increased axonal mitochondrial parameters, as well as ameliorated axonal damage after demyelination with lysolecithin. As the neuronal cell bodies in MS harbour mitochondrial DNA deletions, which affects their physiology, including energy production efficiency, another aim of this thesis was to model this deficiency in vitro. As it was not possible to model these mitochondrial defects in vitro within the experiments of this thesis, the characterization of a mitochondrial mutant in vivo model was done as a contribution to a greater set of experiments performed by other members of the Mahad lab.
5
Papadopoulos, Dimitrios. "Axonal loss and neurodegeneration in the Mog-induced EAE model of multiple sclerosis." Thesis, Imperial College London, 2003. http://ethos.bl.uk/OrderDetails.do?uin=uk.bl.ethos.406559.
Full text
6
Trip, Sachid Anand. "Development of in vivo markers of axonal loss and demyelination in optic neuritis." Thesis, University College London (University of London), 2009. http://discovery.ucl.ac.uk/14258/.
Full textAbstract:
Axonal loss and remyelination are major pathological substrates implicated in the balance between recovery and fixed disability that occurs following optic neuritis and other forms of relapse in multiple sclerosis. Optic neuritis is an ideal model for studying the functional consequences of a single demyelinating lesion. Several quantitative measures of vision can assess function of the anterior visual pathway, and electrophysiological testing can provide measures of axonal integrity and myelination. These measures are highly reproducible and permit the functional relevance of any structural changes to be determined. The studies presented in this thesis applied three retinal imaging techniques and three optic nerve MRI techniques to investigate the extent and functional significance of axonal loss and remyelination following optic neuritis. Two of the retinal imaging measures, optical coherence tomography (OCT) and scanning laser polarimetry, demonstrated functionally relevant neuroaxonal loss in patients with incomplete recovery following optic neuritis. In acute optic neuritis patients, OCT detected retinal nerve fibre layer (RNFL) thinning after three months and quantified acute peripapillary RNFL swelling in bulbar cases. MRI-detected optic nerve atrophy correlated well with OCT RNFL thinning supporting the hypothesis that axonal loss is the major substrate of atrophy. Furthermore, there was evidence from the atrophy study of retrograde degeneration from the optic nerve to RNFL to macula. Optic nerve diffusion tensor imaging demonstrated increased mean diffusivity and reduced fractional anisotropy in nerves affected by optic neuritis compatible with a process of axonal disruption or loss. Optic nerve magnetisation transfer ratio in affected optic nerves correlated with both visual evoked potential latency and RNFL thickness suggesting that MTR may not be an exclusive marker of myelination alone and also reflects co-existent axonal loss. Anterior visual pathway imaging may be useful in monitoring therapies that aim to prevent axonal loss and enhance remyelination in optic neuritis.
7
Smith, Matthew Alan. "Differential Loss of Bidirectional Axonal Transport with Structural Persistence Within The Same Optic Projection of the DBA/2J Glaucomatous Mouse." NEOMED Integrated Pharmaceutical Medicine / OhioLINK, 2014. http://rave.ohiolink.edu/etdc/view?acc_num=ne2mh1401723180.
Full text
8
Palomo, Guerrero Marta. "Papel de CPT1C en el desarrollo axonal y en el transporte de los endosomas tardíos." Doctoral thesis, Universitat Internacional de Catalunya, 2018. http://hdl.handle.net/10803/463046.
Full textAbstract:
La paraplejía espástica hereditaria agrupa un conjunto de desórdenes neurodegenerativos caracterizados por espasticidad y rigidez muscular. Todos ellos están relacionados clínica y patológicamente con problemas en el desarrollo axonal del tracto corticoespinal y las columnas dorsales de la médula espinal.
Hasta la fecha se han descrito 77 genes asociados a esta enfermedad. Sus mutaciones afectan a diversas funciones celulares como el transporte intracelular, la función mitocondrial o el metabolismo lipídico, entre otras. Entre estos genes se encuentra CPT1C.
CPT1C es una carnitina palmitoil transferasa que se encuentra localizada en el RE de neuronas. A diferencias del resto de CPTs, CPT1C no presenta actividad catalítica pero mantiene la capacidad de unir malonil-CoA. El malonil-CoA es un intermediario en la síntesis de ácidos grasos, y sus niveles varían según el estado energético de la célula. Recientemente se ha sugerido que CPT1C podría ser un sensor de malonil-CoA y regular la función de otras proteínas.
Entre las posibles proteínas interactoras de CPT1C se encuentra la protrudina. Se ha descrito el papel de la protrudina en el transporte y desarrollo axonal, pero no cuál es su mecanismo regulador. En esta tesis proponemos que CPT1C podría interaccionar con protrudina y, mediante la unión a malonil-CoA, regular el transporte y desarrollo axonal. Para ello se han realizado dos aproximaciones. En primer lugar se ha estudiado la implicación de CPT1C en el crecimiento axonal y dendrítico en neuronas corticales procedentes de embriones de ratones WT y KO CPT1C. En segundo lugar se ha estudiado la interacción de CPT1C con protrudina y su papel en la localización y transporte de endosomas tardíos en células HeLa. En ambas aproximaciones se ha estudiado la influencia de la unión de malonil-CoA a CPT1C.
Los resultados obtenidos demuestran que CPT1C es necesaria para el correcto crecimiento axonal y ramificación dendrítica dependiendo de su unión a malonil-CoA.
En este trabajo hemos podido demostrar además la interacción de CPT1C con protrudina, y describir su papel en la regulación de la localización y transporte de LEs, función que se encuentra regulada por la unión de malonil-CoA.
9
Vaur, Pauline Magda Marie. "Caractérisation des effets protecteurs du NAD+ et du Nicotinamide Riboside lors de la dégénérescence axonale dans le système nerveux central : Implications dans les processus neurodégénératifs." Thesis, Paris 6, 2016. http://www.theses.fr/2016PA066594/document.
Full textAbstract:
Les maladies neurodégénératives se caractérisent par une déconnexion synaptique et une dégénérescence des axones (DA) précoces, menant à la mort spécifique d’une population neuronale. Les niveaux intracellulaires de NAD+, co-facteur essentiel dans le maintien de l’intégrité axonale, sont fortement diminués lors de ces pathologies. L’augmentation des taux de NAD+ est ainsi une stratégie thérapeutique dans la prévention de ces maladies. La capacité du nicotinamide riboside (NR) à retarder la DA dans le système nerveux périphérique (SNP) ainsi que la récente mise en évidence d'une conversion extracellulaire du NAD+ en NR dans des lignées cellulaires et dans le SNP soulignent l'intérêt de ce précurseur du NAD+. Mon projet de thèse repose sur la caractérisation des effets du NAD+ et du NR lors de la DA dans des neurones du système nerveux central (SNC). A partir d'un modèle d'excitotoxicité mis au point en dispositifs microfluidiques, nous montrons pour la première fois que le NR protège de la DA dans des neurones corticaux de manière plus efficace que le NAD+. Cet effet différentiel a également été validé dans un modèle ischémique in vivo. De manière surprenante, lors d'une neurodégénérescence induite par une déplétion aigüe en NAD+, un effet protecteur total à la fois du NAD+ et du NR a été mis en évidence. L'analyse de la voie de conversion extracellulaire a ainsi révélée une adaptation du métabolisme du NAD+ et de sa conversion en NR en fonction du paradigme neurotoxique. En conclusion, ce travail démontre un fort effet protecteur du NR dans le SNC et ouvre de nouvelles voies thérapeutiques dans la prévention des processus neurodégénératifsSynaptic and axonal degeneration (AxD) are major events in neurodegenerative diseases. Levels of NAD+, an important coenzyme for axonal integrity, are strongly reduced in different degeneration models so enhancing cellular NAD+ is one of the numerous therapeutic strategies against neuronal pathologies. Nicotinamide riboside (NR) is a good NAD+ precursor as it has already been shown to delay AxD in peripheral nervous system (PNS) and extracellular NAD+ conversion to NR was previously described in cell lines and in PNS. During my thesis project, we analyzed the role of NR metabolism to prevent degeneration processes in cortical neurons. Using an excitotoxicity model developed in microfluidic devices, we showed for the first time that both NAD+ and NR delay AxD in cortical neurons, with a more potent effect for NR. We confirm this differential effect in an in vivo ischemic model. Moreover, NR effect is mainly restricted to the axonal compartment and intracellular NAD+ depletion is reverted after NR application, suggesting that axonal integrity is totally dependent on NAD+ local metabolism. Furthermore, in a complete NAD+ depletion paradigm, NAD+ and NR have surprisingly the same strong effect, protecting equally neuronal death and AxD. Examination of the extracellular pathway suggest that NAD+ conversion to NR is limited in excitotoxicity but effective in the NAD+ depletion model. These results reveal that NR and NAD+ metabolism depend on the neurotoxic paradigm. Our results demonstrate that NR has a strong and local neuroprotective effect on AxD in several neurotoxic processes. These findings open new therapeutic strategies to prevent neurodegenerative diseases
10
Bruckert, Hélène. "Caractérisation d'Hrp48, une protéine de liaison aux ARNs, lors de la morphogenèse axonale chez la drosophile." Nice, 2012. http://www.theses.fr/2012NICE4063.
Full textAbstract:
Des études récentes ont montré que le contrôle post-transcriptionnel des ARNms joue un rôle essentiel sur la croissance et le guidage axonal, processus permettant la mise en place de circuits neuronaux. Afin d’étudier ce type de régulation in vivo, mon projet de thèse visait à caractériser Hrp48, une protéine de liaison aux ARNs appartenant à la famille conservée des hnRNPA/B. J’ai montré que l’inactivation d’hrp48 entraîne des défauts de croissance axonale comme des neurones projetant leurs axones dans une mauvaise direction ou au-delà de leur cible classique, défauts remarquablement plus forts chez les femelles que chez les mâles. Mes travaux ont révélé que la protéine femelle-spécifique Sex-léthal s’accumule ectopiquement dans le noyau des cellules mutantes hrp48, ce qui pourrait être à l’origine des défauts sexe-spécifiques de migration axonale observés. En parallèle, j’ai montré que l’inactivation de sema-1a, une cible ARNm putative d’Hrp48, provoque des défauts proches des mutants hrp48, et qu’hrp48 et sema-1a interagissent génétiquement. Par ailleurs, le niveau général d’ARNm sema-1a est plus faible chez les femelles que chez les mâles. Ces résultats suggèrent donc qu’une dérégulation de sema-1a pourrait induire les défauts sexe-spécifiques de croissance axonale observés en contexte mutant hrp48. Ce travail a permis de proposer un modèle préliminaire de régulation post-transcriptionnelle par une protéine de liaison aux ARNs de la famille hnRNPA/B in vivo et a mis en évidence des différences cryptiques entre les femelles et les mâles. Il s’inscrit dans le cadre d’études récentes révélant des différences sexe-spécifiques dans le contrôle de l’expression des gènesRecent studies have shown that post-transcriptional regulatory mechanisms play essential roles in axon growth and guidance, processes involved in the establishment of neuronal circuits during development. To study these mechanisms in vivo, my project aimed at characterizing the role of the RNA-binding protein Hrp48, which belongs to the conserved hnRNP A/B family. I showed that inactivating hrp48 function leads to strong and specific axon migration defects, including axon misguidance and overextension. Notably, I have observed that the frequency of hrp48 mutant phenotypes is much higher in females than in males. Moreover, I showed that the female-specific Sex-lethal protein ectopically accumulates in the nucleus of mutant cells. This abnormal nuclear accumulation could explain the sex-specific defects observed in axonal migration. In parallel, I could show that inactivation of sema-1α, an Hrp48 putative mRNA target, causes defects similar to those observed in hrp48 mutants, and that hrp48 and sema-1 α genetically interact. Moreover, the overall levels of sema-1 α transcripts are much lower in females than in males. These results suggest that sema-1 α misregulation may induce the sex-specific defects in axonal growth observe upon hrp48 downregulation. Tis work has allowed us to propose a preliminary in vivo model for a post-transcriptional regulatory mechanism controlled by a member of the hnRNP A/B family. Furthermore, it has revealed cryptic differences between females and males in the context of recent studies revealing sex-specific differences in the control of gene expression
Books on the topic "Axonal loss"
1
Weir, Andrew. Multiple sclerosis. Edited by Patrick Davey and David Sprigings. Oxford University Press, 2018. http://dx.doi.org/10.1093/med/9780199568741.003.0231.
Full textAbstract:
Multiple sclerosis is an idiopathic inflammatory disorder of the CNS. The characteristic pathological feature is the occurrence of ‘plaques’: well-defined areas of myelin loss, with relative axonal preservation.
2
Donaghy, Michael. Polyneuropathy. Oxford University Press, 2011. http://dx.doi.org/10.1093/med/9780198569381.003.0453.
Full textAbstract:
Typically polyneuropathy will cause the combination of distal limb muscle weakness, loss of tendon reflexes, and reduced distal limb sensation. There is variable involvement of the autonomic innervation, damage to which causes a dry, vasodilated foot or hand. Loss of tendon reflexes is a cardinal sign of polyneuropathy, often restricted to the ankle jerks in axonal degeneration, but involving more proximal reflexes in acquired demyelinating neuropathies which may involve more proximal segments or the nerve roots. Clinical features suggestive of demyelinating or conduction block polyneuropathy include: a relative lack of muscle wasting in relation to the degree of weakness because no denervation has occurred; weakness of proximal muscles as well as distal, because of nerve root involvement; and disproportionate loss of joint position and vibration sensations compared to relative preservation of pain and temperature sensations which are carried by unmyelinated fibres.
3
Teener, James W. Entrapment Neuropathies. Oxford University Press, 2017. http://dx.doi.org/10.1093/med/9780199937837.003.0122.
Full textAbstract:
Entrapment neuropathies are a subset of compression neuropathies caused by chronic impingement upon a nerve by nearby structures. The resulting pathology depends upon the duration and severity of entrapment, and ranges from demyelination if entrapment is mild or brief to axonal loss in more severe cases. Entrapment neuropathies typically cause symptoms referable to a single nerve distribution, but sensory symptoms may appear to extend beyond the typical dermatome of the entrapped nerve. Diagnosis is based upon clinical history and examination, and is supported by electrodiagnostic studies and imaging. A variety of supportive therapies may result in improvement of symptoms, but in cases of severe entrapment, surgical intervention to release the nerve is often necessary, and even then recovery is often incomplete.
4
Franssen, Hessel. Generalized peripheral neuropathies. Oxford University Press, 2016. http://dx.doi.org/10.1093/med/9780199688395.003.0020.
Full textAbstract:
The chapter on generalized peripheral neuropathies describes how to perform and interpret electrophysiological studies aimed at diagnosing polyneuropathy. It first reviews methodological issues, such as stimulation and recording, and takes into account temperature. Next, the relevant pathophysiology of single myelinated axons, as found in animal experiments, is discussed and related to findings on nerve conduction studies performed in patients. This is followed by a discussion of criteria for axon loss and demyelination. Finally, typical findings in specific neuropathies are described and examples of typical findings are shown in the figures.
5
Fink, John K. Upper Motor Neuron Disorders. Oxford University Press, 2017. http://dx.doi.org/10.1093/med/9780199937837.003.0031.
Full textAbstract:
Symptomatic disturbance of corticospinal and corticobulbar tracts (collectively, the upper motor neuron UMN) occurs in innumerable acquired central nervous system disorders including the consequences of trauma, hypoxia-ischemia, inflammation (e.g. multiple sclerosis), toxins (e.g. thiocyanate1 and specific organophosphorus compound toxicity2) and deficiencies (e.g. hypocupremia3 and vitamin B12 deficiency). Variable degrees of UMN disturbance frequently accompany degenerative disorders in which disturbance of another neurologic system results in the primary clinical. Neuropathologic studies have shown prominent axon degeneration involving corticospinal tracts (HSP and PLS) and corticobulbar tracts (PLS); and mildly affecting dorsal columns (HSP and PLS to some degree). Myelin loss is considered secondary to axon degeneration. Loss of cortical motor neurons is observed in PLS. Anterior horn cells are typically spared in both HSP and PLS. Presently, treatment for HSP and PLS is symptomatic and includes physical therapy and spasticity reducing medications.
6
Montgomery, Erwin B. Approach to DBS in the Vicinity of the Subthalamic Nucleus. Oxford University Press, 2016. http://dx.doi.org/10.1093/med/9780190259600.003.0011.
Full textAbstract:
The regional anatomy around the DBS lead in the subthalamic nucleus (STN) determines efficacy and adverse effects. Understanding the regional anatomy allows the programmer to adjust the stimulation to provide optimal benefit and the absence of adverse effects.The STN lies near the junction of the diencephalon and mesencephalon. It is just ventral to the thalamus, just lateral to the brachium conjunctivum and red nucleus, and medial and dorsal to the internal capsule. These structures are important because inappropriate stimulation causes side effects. For examples: Electrical fields spreading to ascending sensory medial lemniscus and spinothalamic pathways behind the STN produce paresthesias. Inadvertent stimulation of the brachium conjunctivum can cause ataxia and loss of balance. The red nucleus lies in the brachium conjunctivum, and the exiting axons from the oculomotor nucleus run within the red nucleus. Electrical fields spreading to these structures can result in disconjugate gaze and diplopia. Stimulating the internal capsule laterally or dorsally can cause tonic muscle contractions.
Book chapters on the topic "Axonal loss"
1
Bjartmar, C., and B. D. Trapp. "Axonal Loss in Multiple Sclerosis." In Magnetic Resonance Spectroscopy in Multiple Sclerosis, 15–32. Milano: Springer Milan, 2001. http://dx.doi.org/10.1007/978-88-470-2109-9_3.
Full text
2
Dutta, Ranjan, Jacqueline Chen, Nobuhiko Ohno, Daniel Ontaneda, and Bruce D. Trapp. "Axonal Loss and Neurodegeneration in Multiple Sclerosis." In Neurodegeneration, 238–47. Oxford, UK: John Wiley & Sons, Ltd, 2017. http://dx.doi.org/10.1002/9781118661895.ch20.
Full text
3
van der Knaap, Marjo S., and Jacob Valk. "Wallerian Degeneration and Myelin Loss Secondary to Neuronal and Axonal Degeneration." In Magnetic Resonance of Myelin, Myelination, and Myelin Disorders, 422–27. Berlin, Heidelberg: Springer Berlin Heidelberg, 1995. http://dx.doi.org/10.1007/978-3-662-03078-3_69.
Full text
4
Torroja, L., M. Packard, V. Budnik, and K. White. "Overexpression of APPL, a Drosophila APP Homologue, Compromises Microtubule Associated Axonal Transport and Promotes Synapse Formation." In Neurodegenerative Disorders: Loss of Function Through Gain of Function, 159–71. Berlin, Heidelberg: Springer Berlin Heidelberg, 2001. http://dx.doi.org/10.1007/978-3-662-04399-8_12.
Full text
5
Criste, Gerson, Bruce Trapp, and Ranjan Dutta. "Axonal loss in multiple sclerosis." In Handbook of Clinical Neurology, 101–13. Elsevier, 2014. http://dx.doi.org/10.1016/b978-0-444-52001-2.00005-4.
Full text
6
Santana Dias, Mariana, Victor Guedes de Araujo, Rafael Lani-Louzada, Rafael Linden, Vinicius Toledo Ribas, and Hilda Petrs-Silva. "Perspective on Gene Therapy for Glaucoma." In Glaucoma - Recent Advances and New Perspectives [Working Title]. IntechOpen, 2022. http://dx.doi.org/10.5772/intechopen.104295.
Full textAbstract:
Glaucoma is a chronic and multifactorial neurodegenerative disease marked by structural damage to the optic nerve with axonal loss, progressive retinal ganglion cell degeneration, and optic disc excavation. Both high intraocular pressure and aging are important risk factors, but not essential to the progression of glaucomatous neurodegeneration. Current treatments are based on controlling intraocular pressure, which is not always effective in avoiding the progression of visual loss. In this sense, novel therapeutic strategies to glaucoma should aim to promote the neuroprotection of both the cell soma of retinal ganglion cells and the axons of the optic nerve. Gene therapy is a new therapeutical approach to glaucoma with a great capacity to overcome neurodegeneration. It consists of the transfer of exogenous genetic material to target cells with a therapeutic purpose. Gene therapy strategies for glaucoma include both the neuroprotection aiming to prevent cell soma and axonal loss and the regeneration of optic nerve axons. In this chapter, we review the most promising current gene therapies for glaucoma that address the various aspects of glaucoma pathology. We also discuss the potential of combining neuroprotective and regenerative strategies to reach a synergic effect for the treatment of glaucoma.
7
Berini, Sarah E., and Nathan P. Staff. "Peripheral Nerve Disorders." In Mayo Clinic Neurology Board Review, edited by Kelly D. Flemming, 760–71. Oxford University Press, 2021. http://dx.doi.org/10.1093/med/9780197512166.003.0087.
Full textAbstract:
Disorders of the peripheral nerves are some of the most common conditions that neurologists face in clinical practice. The wide differential diagnosis that often accompanies peripheral nerve disorders may be narrowed by careful attention to the history (time course, severity, preexisting disease, and family history); peripheral neuroanatomy; patient symptomatology (sensory loss, paresthesia, pain, and weakness); and neurologic examination (sensory loss, weakness, atrophy, and reduced muscle stretch reflexes). Electromyography is used to assess large-diameter myelinated axons (touch, pressure, vibration, proprioception, and motor) and aid in localization by helping to narrow the differential diagnosis and predict axonal or demyelinating pathophysiology.
8
Klein, Christopher J. "Painless, Symmetric, Ascending Weakness and Sensory Loss." In Mayo Clinic Cases in Neuroimmunology, edited by Andrew McKeon, B. Mark Keegan, and W. Oliver Tobin, 131–34. Oxford University Press, 2021. http://dx.doi.org/10.1093/med/9780197583425.003.0042.
Full textAbstract:
A 60-year-old man sought care for painless, symmetric, ascending weakness and sensory loss affecting the lower, greater than upper, extremities, progressing over 3 weeks with associated orthostatism. He was diffusely areflexic and had symmetric weakness, distal greater than proximal, with normal bulbar strength. Muscle atrophy was not appreciated, and fasciculations were absent. Sensory examination revealed pan-sensory loss at the feet and hands. His gait was unsteady with prominent steppage. He was unable to climb stairs, kneel, or arise without assistance. Pertinent medical and social history included a spinal fusion at C5-T1, a 10-pack-year smoking history, and congestive heart failure, New York Heart Association class III with an intracardiac defibrillator for ventricular fibrillation, and taking carvedilol and furosemide. Needle electromyography and nerve conduction studies showed a severe axonal sensory-motor polyneuropathy with proximal involvement, suggesting polyradicular colocalization. Cerebrospinal fluid obtained during unremarkable spinal myelography, for exclusion of spinal compression, showed normal and abnormal findings: total nucleated cells, 3/µL; glucose, 87 mg/dL; and protein, 326 mg/dL. Sural nerve biopsy showed marked active axonal injury without significant inflammatory infiltrates. Expanded autoimmune neuroimmunologic testing by indirect immunofluorescence staining identified the classic pattern for antineuronal nuclear antibody type 1 –immunoglobulin G. Chest radiography and computed tomography showed a consolidation and volume loss in the left lower lobe without identifiable mass. The patient was diagnosed with paraneoplastic axonal sensory-motor polyneuropathy in the setting of antineuronal nuclear antibody type 1-immunoglobulin G positivity and likely small cell lung carcinoma. Acute motor axonal neuropathy was thought to be the diagnosis, and the patient was treated with plasma exchange. He continued to worsen and was transferred to the intensive care unit with new shortness of breath. Escalated therapy with intravenous immunoglobulin did not help. He had development of urinary retention, bulbar weakness, confusion, and flail limbs in all extremities. On identification of antineuronal nuclear antibody type 1-immunoglobulin G, he was treated with intravenous methylprednisolone, but his condition worsened. The patient and his family opted for comfort measures. His defibrillator was turned off, and he died 20 days after first coming to the hospital. At autopsy, small cell lung carcinoma of the left lung was identified without bronchial mass or metastasis. Neural tissues had diffuse microglial activation, with scattered microglial nodules and prominent perivascular chronic lymphocytic infiltrates. Antineuronal nuclear antibody type 1-immunoglobulin G autoimmunity was first reported in 1965. Patients had sensory neuropathy with nonmetastatic cancer and dorsal ganglia degeneration at autopsy. Neuropathy is the most common neurologic presentation, but the neurologic phenotypes have expanded since the original descriptions to include cerebellar, cognitive, and spinal cord involvement.
9
Foster, Paul J., Anthony Khawaja, Lisanne J. Balk, Zaynah Muthy, and Axel Petzold. "Sensory loss—vision." In Oxford Textbook of Neurologic and Neuropsychiatric Epidemiology, edited by Carol Brayne, Valery L. Feigin, Lenore J. Launer, and Giancarlo Logroscino, 345–54. Oxford University Press, 2020. http://dx.doi.org/10.1093/med/9780198749493.003.0033.
Full textAbstract:
This chapter focuses on degenerative optic neuropathy. The retina and optic nerve share their embryological origin with the brain and are widely regarded as part of the central nervous system. Retinal microvasculature and neuronal components offer a unique ‘window’ on tissues that are closely allied to intracranial structures. Consequently, the eye is vulnerable to the same processes that cause neurodegenerative diseases. Axonal damage in the brain may affect the retinal nerve fibre layer (RNFL), the inner plexiform, and ganglion cell layers, halting at the level of the inner nuclear layer. On this basis, it seems that it is likely that patterns and trends in the inner retinal layers mirror those in the brain, and that these patterns may reflect wider risk of neurodegenerative changes. The dementias and Parkinson’s disease are associated with measurable changes in the retina and optic nerve. Two specific forms of degenerative optic neuropathy that deserve special consideration on the basis of their greater frequency are glaucoma and multiple sclerosis (MS) associated optic neuritis (MSON).
10
M., Zachary, and Jacob A. "Mechanisms and Patterns of Axonal Loss in Multiple Sclerosis." In Neurodegeneration. InTech, 2012. http://dx.doi.org/10.5772/35703.
Full textConference papers on the topic "Axonal loss"
1
Fournier, Adam, Suneil Hosmane, and K. T. Ramesh. "Thresholds for Embryonic CNS Axon Integrity, Degeneration, and Regrowth Using a Focal Compression Platform." In ASME 2012 Summer Bioengineering Conference. American Society of Mechanical Engineers, 2012. http://dx.doi.org/10.1115/sbc2012-80331.
Full textAbstract:
Traumatic axonal injuries (TAI) are broadly defined as the focal or multi-focal damage of axons within white matter tracts of the central nervous system (CNS), and can occur in the setting of spinal cord injury (SCI) and traumatic brain injury (TBI). TAI can result from mechanical forces associated with the rapid deformation of white matter regions during trauma. Through combinations of compression, stretch, and shear, axon injury often results in an irreversible loss of functional neural connectivity, since the scope for axonal regeneration in the CNS is extremely limited.
2
Sotudeh-Chafi, M., N. Abolfathi, A. Nick, V. Dirisala, G. Karami, and M. Ziejewski. "A Multi-Scale Finite Element Model for Shock Wave-Induced Axonal Brain Injury." In ASME 2008 Summer Bioengineering Conference. American Society of Mechanical Engineers, 2008. http://dx.doi.org/10.1115/sbc2008-192342.
Full textAbstract:
Traumatic brain injuries (TBIs) involve a significant portion of human injuries resulting from a wide range of civilian accidents as well as many military scenarios. Axonal damage is one of the most common and important pathologic features of traumatic brain injury. Axons become brittle when exposed to rapid deformations associated with brain trauma. Accordingly, rapid stretch of axons can damage the axonal cytoskeleton, resulting in a loss of elasticity and impairment of axoplasmic transport. Subsequent swelling of the axon occurs in discrete bulb formations or in elongated varicosities that accumulate organelles. Ultimately, swollen axons may become disconnected [1]. The shock waves generated by a blast, subject all the organs in the head to displacement, shearing and tearing forces. The brain is especially vulnerable to these forces — the fronts of compressed air waves cause rapid forward or backward movements of the head, so that the brain rattles against the inside of the skull. This can cause subdural hemorrhage and contusions. The forces exerted on the brain by shock waves are known to damage axons in the affected areas. This axonal damage begins within minutes of injury, and can continue for hours or days following the injury [2]. Shock waves are also known to damage the brain at the subcellular level, but exactly how remains unclear. Kato et al., [3] described the effects of a small controlled explosion on rats’ brain tissue. They found that high pressure shock waves led to contusions and hemorrhage in both cortical and subcortical brain regions. Based on their result, the threshold for shock wave-induced brain injury is speculated to be under 1 MPa. This is the first report to demonstrate the pressure-dependent effect of shock wave on the histological characteristics of brain tissue. An important step in understanding the primary blast injury mechanism due to explosion is to translate the global head loads to the loading conditions, and consequently damage, of the cells at the local level and to project cell level and tissue level injury criteria towards the level of the head. In order to reach this aim, we have developed a multi-scale non-linear finite element modeling to bridge the micro- and macroscopic scales and establish the connection between microstructure and effective behavior of brain tissue to develop acceptable injury threshold. Part of this effort has been focused on measuring the shock waves created from a blast, and studying the response of the brain model of a human head exposed to such an environment. The Arbitrary Lagrangian Eulerian (ALE) and Fluid/Solid Interactions (FSI) formulation have been used to model the brain-blast interactions. Another part has gone into developing a validated fiber-matrix based micro-scale model of a brain tissue to reproduce the effective response and to capturing local details of the tissue’s deformations causing axonal injury. The micro-model of the axon and matrix is characterized by a transversely isotropic viscoelastic material and the material model is formulated for numerical implementation. Model parameters are fit to experimental frequency response of the storage and loss modulus data obtained and determined using a genetic algorithm (GA) optimizing method. The results from macro-scale model are used in the micro-scale brain tissue to study the effective behavior of this tissue under injury-based loadings. The research involves the development of a tool providing a better understanding of the mechanical behavior of the brain tissue against blast loads and a rational multi-scale approach for driving injury criteria.
3
Ayyalasomayajula, Avinash, and Jonathan Vande Geest. "Determining Heterogeneity in the Scleral Shell Using an Inverse Mechanics Approach." In ASME 2013 Summer Bioengineering Conference. American Society of Mechanical Engineers, 2013. http://dx.doi.org/10.1115/sbc2013-14747.
Full textAbstract:
One of the important events leading to loss of vision in primary open-angle glaucoma — the 2 nd leading cause of blindness in the US [1] — is the death of retinal ganglion cells. Previous research has established a strong correlation between elevated intraocular pressure (IOP) and the incidence of glaucoma [2]. Stiffening of ocular tissues (like sclera) and axonal damage in the optic nerve head (ONH) were found to occur in response to elevated IOPs [3, 4]. As such, the biomechanical environment in and around the ONH, which is surrounded by the sclera and through which the visual information exits the eye, could be important in the incidence of this disease. Additionally, race and ethnicity factors were found to affect the incidence of glaucoma [5].
4
Wu, Xuehai, and Assimina A. Pelegri. "Deep 3D Convolution Neural Network Methods for Brain White Matter Hybrid Computational Simulations." In ASME 2020 International Mechanical Engineering Congress and Exposition. American Society of Mechanical Engineers, 2020. http://dx.doi.org/10.1115/imece2020-24664.
Full textAbstract:
Abstract Material properties of brain white matter (BWM) show high anisotropy due to the complicated internal three-dimensional microstructure and variant interaction between heterogeneous brain-tissue (axon, myelin, and glia). From our previous study, finite element methods were used to merge micro-scale Representative Volume Elements (RVE) with orthotropic frequency domain viscoelasticity to an integral macro-scale BWM. Quantification of the micro-scale RVE with anisotropic frequency domain viscoelasticity is the core challenge in this study. The RVE behavior is expressed by a viscoelastic constitutive material model, in which the frequency-related viscoelastic properties are imparted as storage modulus and loss modulus for the composite comprised of axonal fibers and extracellular glia. Using finite elements to build RVEs with anisotropic frequency domain viscoelastic material properties is computationally very consuming and resource-draining. Additionally, it is very challenging to build every single RVE using finite elements since the architecture of each RVE is arbitrary in an infinite data set. The architecture information encoded in the voxelized location is employed as input data and is consequently incorporated into a deep 3D convolution neural network (CNN) model that cross-references the RVEs’ material properties (output data). The output data (RVEs’ material properties) is calculated in parallel using an in-house developed finite element method, which models RVE samples of axon-myelin-glia composites. This novel combination of the CNN-RVE method achieved a dramatic reduction in the computation time compared with directly using finite element methods currently present in the literature.
5
Borges, Isabella Sabião, João Victor Aguiar Moreira, Eustaquio Costa Damasceno Junior, Alencar Pereira dos Santos, Gabriela Tomás Alves, Leonardo Peixoto Garcia, Maria Fernanda Prado Rosa, et al. "Chronic inflammatory demyelinating polyradiculoneuropathy induced by paclitaxel." In XIII Congresso Paulista de Neurologia. Zeppelini Editorial e Comunicação, 2021. http://dx.doi.org/10.5327/1516-3180.413.
Full textAbstract:
Background: Peripheral neuropathies in cancer are most often due to neurotoxic chemotherapeutic agents. Approximately 30% of patients receiving neurotoxic chemotherapy (CTX) will suffer from chemotherapy-induced peripheral neuropathy (CIPN). Paclitaxel is an extremely effective chemotherapeutic agent for the treatment of breast, ovarian, and lung cancer. However, paclitaxel-induced peripheral neuropathy occurs in 59-87% of patients who receive this drug. Paclitaxel is an anti-tubulin drug that causes microtubule stabilization, resulting in distal axonal degeneration, secondary demyelination and nerve fiber loss. Case: We present a case of a 68-year-old female patient with history of breast cancer who presented sensorial ataxia and progressive muscle weakness two months after starting CTX with paclitaxel. The physical examination showed tetraparesis with proximal predominance, areflexia, severe hypopalesthesia and postural instability. Electroneuromyography showed the existence of asymmetric demyelinating polyradiculoneuropathy, with conduction block and temporal dispersion in practically all evaluated nerves. The cerebrospinal fluid confirmed the albumin-cytological dissociation. Chronic inflammatory demyelinating polyradiculoneuropathy (CIDP) was confirmed and patient underwent monthly treatment with methylprednisolone with good response. Discussion: Evidences has implicated neuroinflammation in the development of PIPN. While most CTX drugs do not cross the blood-brain-barrier, they readily penetrate the blood-nerve-barrier and bind to and accumulate in dorsal root ganglia and peripheral axons. CTX can induce neuroinflammation through activation of immune and immune- like glial cells. In fact, immune cells (e.g., macrophages, lymphocytes) and glial cells (e.g., Schwann cells) in the peripheral nervous system play important role in the induction and maintenance of neuropathy. Conclusion: CIDP should be included in the spectrum of CIPN.
6
Long, Yu, Changhong Zhang, Ning Zhang, Yong Huang, and Xuejun Wen. "Formation of Highly Aligned Grooves on the Inner Surface of Semi-Permeable Hollow Fiber Membrane for the Directional Axonal Outgrowth." In ASME 2005 International Mechanical Engineering Congress and Exposition. ASMEDC, 2005. http://dx.doi.org/10.1115/imece2005-81235.
Full textAbstract:
It is generally believed that organized neural architecture is essential for both nervous system development, function, and regeneration. In the absence of guidance cues, regenerating axons may lose their directions and become misaligned, resulting in the formation of neuromas and/or misappropriate connections. To help regenerate axons across damaged regions and guide them to appropriate targets, some bridging devices such as microgrooves are being intensively researched to achieve a better directional axonal growth. This paper reports a novel fabrication process to generate a highly aligned groove texture on the inner surface of semi-permeable hollow fiber membranes (HFMs). HFMs were shown to be one of the most promising results in guiding axonal regeneration [1]. The fabrication process utilized a wet phase inversion procedure with polyurethane as model polymer, dimethyl sulfoxide (DMSO) as solvent, and water as nonsolvent. Data indicated that highly aligned groove texture could be formed on the HFM inner surface by carefully controlling phase inversion conditions such as the polymer solution flow rate, and/or nonsolvent flow rate, and/or polymer solution concentration ratio. The texture forming mechanism is qualitatively explained using a polyurethane (PU)-DMSO-water ternary phase diagram and the process dynamics. Axonal outgrowth on the HFM with aligned grooves showed the highly aligned orientation and improved axonal outgrowth length. This study will eventually lead to a new and effective way to engineer nerve grafts based on a highly aligned three dimensional scaffold for the spinal cord injury and nerve damage treatment.
7
Musso, Alexandre Amaral, Maria Rufina Barros, and Ryann Pancieri Paseto. "Chronic Inflammatory Demyelinating Polyradiculoneuropathy (CIDP) as a presentation of Familial Amyloid Polyneuropathy (FAP): diagnostic error or overlap?" In XIII Congresso Paulista de Neurologia. Zeppelini Editorial e Comunicação, 2021. http://dx.doi.org/10.5327/1516-3180.640.
Full textAbstract:
Case report: Male, 72 years old, with progressive tetraparesis, paraesthesia and burning pain with distal predominance. Electroneuromyography (ENMG) showed findings suggestive of sensory-motor axonal polyneuropathy and signs of active and chronic denervation in the L5 and S1 territory. Underwent lumbar arthrodesis and during surgery, presented symptomatic bradycardia requiring a pacemaker. He reported partial pain improvement, but had bilateral foot drop and bladder retention. New ENMG demonstrated findings, now suggestive of CIDP. Underwent intravenous corticosteroid therapy without improvement. In 2019, he presented dysphagia for solids, weight loss, erectile dysfunction, postural hypotension and sensory-motor worsening. Underwent Human Immunoglobulin for 6 months. As there was no improvement, he was referred to our service. Best analysis in history revealed heart disease in 3 siblings. Genetic sequencing was performed for FAP that demonstrated a VAL50MET mutation. Context: FAP is an autosomal dominant inherited disease, caused by mutations in the transthyretin (TTR) gene that determine the accumulation of abnormal protein aggregates. Peripheral neuropathy differs from classic CIDP pattern by the distribution of weakness, important impairment of fine fibers and refractoriness to immunosuppressive treatment. Conclusions: FAP is a serious and treatable condition. Early diagnosis has a huge impact on life quality. Although confusion with CIDP is frequent, it is possible through history to differentiate these conditions.
8
Sigal, Ian A., Hongli Yang, Michael D. Roberts, Claude F. Burgoyne, and J. Crawford Downs. "Biomechanics of the Posterior Pole During the Remodeling Progression From Normal to Early Experimental Glaucoma." In ASME 2009 Summer Bioengineering Conference. American Society of Mechanical Engineers, 2009. http://dx.doi.org/10.1115/sbc2009-206518.
Full textAbstract:
Glaucoma is one of the leading causes of blindness worldwide. The loss of vision associated with glaucoma is due to damage to the retinal ganglion cell axons, which transmit visual information to the brain. Damage to these axons is believed to occur as the axons pass through the lamina cribrosa (LC), a connective tissue structure in the optic nerve head at the back of the eye. Elevated intraocular pressure (IOP) has been identified as the main risk factor for the development of the neuropathy, but the mechanism(s) by which a mechanical insult (elevated IOP) is translated into a biological effect (glaucomatous optic neuropathy) is not well understood.
9
Grytz, Rafael, Ian A. Sigal, Jeffrey W. Ruberti, and J. Crawford Downs. "Microstructure Motivated Growth and Remodeling of the Lamina Cribrosa in Early Glaucoma." In ASME 2011 Summer Bioengineering Conference. American Society of Mechanical Engineers, 2011. http://dx.doi.org/10.1115/sbc2011-53780.
Full textAbstract:
Glaucoma is a leading cause of blindness in the world and is due to the loss of retinal ganglion cell axons. These axons deteriorate in a region in the posterior pole of the eye known as the optic nerve head (ONH). The axons pass through the lamina cribrosa (LC) as they exit the eye at the ONH. The LC is characterized by a porous, connective tissue structure composed of laminar beams. The function of the LC is unclear, but is believed to include providing mechanical support to the axons as they transition from inside the pressurized globe to the lower pressure orbital space. Early experimental glaucoma studies have shown that the LC remodels into a thicker, more posterior structure which incorporates more connective tissue after chronic IOP elevation [1,2]. The process by which this occurs is unknown. These structural changes are assumed to play an important role in the pathophysiology of the ocular disease glaucoma, where elevated IOP is known to be the most relevant risk factor.
10
Rajabi, Shadi, Craig A. Simmons, and C. Ross Ethier. "Design of Experiments for Exposure of Astrocytes to Elevated Hydrostatic Pressure and Hypoxia." In ASME 2008 Summer Bioengineering Conference. American Society of Mechanical Engineers, 2008. http://dx.doi.org/10.1115/sbc2008-192558.
Full textAbstract:
Glaucoma, a chronic optic neuropathy, is the second most common cause of blindness, affecting 67 million people worldwide. The damage in glaucoma occurs at the optic nerve head (ONH), where the axons of the retinal ganglion cells leave the eye posteriorly. Glaucoma is frequently associated with elevated intraocular pressure (IOP), and visual field loss can be prevented by significant lowering of IOP. Hence, the role of pressure in glaucoma is important. Unfortunately, the mechanism by which pressure leads to vision loss in glaucoma is very poorly understood.
Reports on the topic "Axonal loss"
1
Song, Sheng-Kwei, William M. Spees, Peng Sun, Yong Wang, and Anne Cross. Noninvasive Detection and Differentiation of Axonal Injury/Loss, Demyelination, and Inflammation. Fort Belvoir, VA: Defense Technical Information Center, October 2014. http://dx.doi.org/10.21236/ada613483.
Full text