308:, also called keratosulfate, is formed from repeating disaccharide galactose units and N-acetylglucosamines. It is also 6-sulfated. This sulfation is crucial to the elongation of the keratan sulfate chain. A study was done using N-acetylglucosamine 6-O-sulfotransferase-1 deficient mice. The wild type mouse showed a significant up regulation of mRNA expressing N-acetylglucosamine 6-O-sulfotransferase-1 at the site of cortical injury. However, in the N-acetylglucosamine 6-O-sulfotransferase-1 deficient mice, the expression of keratan sulfate was significantly decreased when compared to the wild type mice. Similarly, glial scar formation was significantly reduced in the N-acetylglucosamine 6-O-sulfotransferase-1 mice, and as a result, nerve regeneration was less inhibited.
141:). While the peripheral nervous system has an intrinsic ability for repair and regeneration, the central nervous system is, for the most part, incapable of self-repair and regeneration. There is currently no treatment for recovering human nerve-function after injury to the central nervous system. Multiple attempts at nerve re-growth across the PNS-CNS transition have not been successful. There is simply not enough knowledge about regeneration in the central nervous system. In addition, although the peripheral nervous system has the capability for regeneration, much research still needs to be done to optimize the environment for maximum regrowth potential. Neuroregeneration is important clinically, as it is part of the
611:. In allografts, the tissue for the graft is taken from another person, the donor, and implanted in the recipient. Xenografts involve taking donor tissue from another species. Allografts and xenografts have the same disadvantages as autografts, but in addition, tissue rejection from immune responses must also be taken into account. Often immunosuppression is required with these grafts. Disease transmission also becomes a factor when introducing tissue from another person or animal. Overall, allografts and xenografts do not match the quality of outcomes seen with autografts, but they are necessary when there is a lack of autologous nerve tissue.
248:, which axons cannot grow across. The proximal segment attempts to regenerate after injury, but its growth is hindered by the environment. It is important to note that central nervous system axons have been proven to regrow in permissive environments; therefore, the primary problem to central nervous system axonal regeneration is crossing or eliminating the inhibitory lesion site. Another problem is that the morphology and functional properties of central nervous system neurons are highly complex, for this reason a neuron functionally identical cannot be replaced by one of another type (
164:
270:
instance, transforming growth factors B-1 and -2, interleukins, and cytokines play a role in the initiation of scar formation. The accumulation of reactive astrocytes at the site of injury and the up regulation of molecules that are inhibitory for neurite outgrowth contribute to the failure of neuroregeneration. The up-regulated molecules alter the composition of the extracellular matrix in a way that has been shown to inhibit neurite outgrowth extension. This scar formation involves several cell types and families of molecules.
531:. If a large segment of nerve is harmed, as can happen in a crush or stretch injury, the nerve will need to be exposed over a larger area. Injured portions of the nerve are removed. The cut nerve endings are then carefully reapproximated using very small sutures. The nerve repair must be covered by healthy tissue, which can be as simple as closing the skin or it can require moving skin or muscle to provide healthy padded coverage over the nerve. The type of anesthesia used depends on the complexity of the injury. A
557:: Sharp injuries, such as a knife wound, damage only a very short segment of the nerve, availing for direct suture. In contrast, nerves that are divided by stretch or crush may be damaged over long segments. These nerve injuries are more difficult to treat and generally have a poorer outcome. In addition, associated injuries, like injury to bone, muscle and skin, can make nerve recovery more difficult.
583:
sutured over the window. Regenerating axons are redirected into the stump. Efficacy of this technique is partially dependent upon the degree of partial neurectomy performed on the donor, with increasing degrees of neurectomy giving rise to increasing axon regeneration within the lesioned nerve, but with the consequence of increasing deficit to the donor.
564:: After a nerve is repaired, the regenerating nerve endings must grow all the way to their target. For example, a nerve injured at the wrist that normally provides sensation to the thumb must grow to the end of the thumb in order to provide sensation. The return of function decreases with increased distance over which a nerve must grow.
550:: Recovery of a nerve after surgical repair depends mainly on the age of the patient. Young children can recover close-to-normal nerve function. In contrast, a patient over 60 years old with a cut nerve in the hand would expect to recover only protective sensation; that is, the ability to distinguish hot/cold or sharp/dull.
222:
environment. The hostile, non-permissive growth environment is, in part, created by the migration of myelin-associated inhibitors, astrocytes, oligodendrocytes, oligodendrocyte precursors, and microglia. The environment within the CNS, especially following trauma, counteracts the repair of myelin and
192:
site in order to clear away debris such as damaged tissue which is inhibitory to regeneration. When a nerve axon is severed, the end still attached to the cell body is labeled the proximal segment, while the other end is called the distal segment. After injury, the proximal end swells and experiences
586:
Some evidence suggests that local delivery of soluble neurotrophic factors at the site of autologous nerve grafting may enhance axon regeneration within the graft and help expedite functional recovery of a paralyzed target. Other evidence suggests that gene-therapy induced expression of neurotrophic
573:
Currently, autologous nerve grafting, or a nerve autograft, is known as the gold standard for clinical treatments used to repair large lesion gaps in the peripheral nervous system. It is important that nerves are not repaired under tension, which could otherwise happen if cut ends are reapproximated
171:
Neuroregeneration in the peripheral nervous system (PNS) occurs to a significant degree. After an injury to the axon, peripheral neurons activate a variety of signaling pathways which turn on pro-growth genes, leading to reformation of a functional growth cone and regeneration. The growth of these
205:
within hours of the injury; the axons and myelin degenerate, but the endoneurium remains. In the later stages of regeneration the remaining endoneurial tube directs axon growth back to the correct targets. During
Wallerian degeneration, Schwann cells grow in ordered columns along the endoneurial
582:
When appropriate, a nearby donor may be used to supply innervation to lesioned nerves. Trauma to the donor can be minimized by utilizing a technique known as end-to-side repair. In this procedure, an epineurial window is created in the donor nerve and the proximal stump of the lesioned nerve is
269:
scar formation is induced following damage to the nervous system. In the central nervous system, this glial scar formation significantly inhibits nerve regeneration, which leads to a loss of function. Several families of molecules are released that promote and drive glial scar formation. For
243:
Slower degeneration of the distal segment than that which occurs in the peripheral nervous system also contributes to the inhibitory environment because inhibitory myelin and axonal debris are not cleared away as quickly. All these factors contribute to the formation of what is known as a
578:
for axonal regeneration across the gap. However, this is not a perfect treatment; often the outcome is only limited function recovery. Also, partial de-innervation is frequently experienced at the donor site, and multiple surgeries are required to harvest the tissue and implant it.
303:
Like the chondroitin sulfate proteoglycans, keratan sulfate proteoglycan (KSPG) production is up regulated in reactive astrocytes as part of glial scar formation. KSPGs have also been shown to inhibit neurite outgrowth extension, limiting nerve regeneration.
639:
A direction of research is towards the use of drugs that target remyelinating inhibitor proteins, or other inhibitors. Possible strategies include vaccination against these proteins (active immunisation), or treatment with previously created antibodies
793:
Prang P, MĂŒller R, Eljaouhari A, Heckmann K, Kunz W, Weber T, Faber C, Vroemen M, Bogdahn U, Weidner N (July 2006). "The promotion of oriented axonal regrowth in the injured spinal cord by alginate-based anisotropic capillary hydrogels".
630:
in order to guide axonal regrowth. The creation of artificial nerve conduits is also known as entubulation because the nerve ends and intervening gap are enclosed within a tube composed of biological or synthetic materials.
1806:
Karnezis T, Mandemakers W, McQualter JL, Zheng B, Ho PP, Jordan KA, Murray BM, Barres B, Tessier-Lavigne M, Bernard CC (July 2004). "The neurite outgrowth inhibitor Nogo A is involved in autoimmune-mediated demyelination".
1694:
Shiotani A, O'Malley BW, Coleman ME, Alila HW, Flint PW (September 1998). "Reinnervation of motor endplates and increased muscle fiber size after human insulin-like growth factor I gene transfer into the paralyzed larynx".
295:(CS-GAGs), are covalently coupled to the protein core CSPGs. CSPGs have been shown to inhibit regeneration in vitro and in vivo, but the role that the CSPG core protein vs. CS-GAGs had not been studied until recently.
290:
pathway is involved. Chondroitin sulfate proteoglycans (CSPGs) have been shown to be up regulated in the central nervous system (CNS) following injury. Repeating disaccharides of glucuronic acid and galactosamine,
235:
rapidly form, and the glia actually produce factors that inhibit remyelination and axon repair; for instance, NOGO and NI-35. The axons themselves also lose the potential for growth with age, due to a decrease in
1273:
De Winter F, Oudega M, Lankhorst AJ, Hamers FP, Blits B, Ruitenberg MJ, Pasterkamp RJ, Gispen WH, Verhaagen J (May 2002). "Injury-induced class 3 semaphorin expression in the rat spinal cord".
193:
some retrograde degeneration, but once the debris is cleared, it begins to sprout axons and the presence of growth cones can be detected. The proximal axons are able to regrow as long as the
1852:"Application of neutralizing antibodies against NI-35/250 myelin-associated neurite growth inhibitory proteins to the adult rat cerebellum induces sprouting of uninjured purkinje cell axons"
201:(also known as the endoneurial tube or channel). Human axon growth rates can reach 2 mm/day in small nerves and 5 mm/day in large nerves. The distal segment, however, experiences
390:(Semaphorin 3A) is present in the scar that forms in both central nervous system and peripheral nerve injuries and contributes to the outgrowth-inhibitory properties of these scars
218:
Unlike peripheral nervous system injury, injury to the central nervous system is not followed by extensive regeneration. It is limited by the inhibitory influences of the glial and
286:. Astrocytes are a predominant type of glial cell in the central nervous system that provide many functions including damage mitigation, repair, and glial scar formation. The
1968:
1015:
Bregman BS, Kunkel-Bagden E, Schnell L, Dai HN, Gao D, Schwab ME (November 1995). "Recovery from spinal cord injury mediated by antibodies to neurite growth inhibitors".
523:. The injured nerve is identified and exposed so that normal nerve tissue can be examined above and below the level of injury, usually with magnification, using either
1565:
Kalantarian B, Rice DC, Tiangco DA, Terzis JK (October 1998). "Gains and losses of the XII-VII component of the "baby-sitter" procedure: a morphometric analysis".
1651:
Fansa H, Schneider W, Wolf G, Keilhoff G (July 2002). "Influence of insulin-like growth factor-I (IGF-I) on nerve autografts and tissue-engineered nerve grafts".
645:
336:
328:
1961:
76:(CNS) by the functional mechanisms involved, especially in the extent and speed of repair. When an axon is damaged, the distal segment undergoes
849:
742:
206:
tube, creating a band of BĂŒngner cells that protects and preserves the endoneurial channel. Also, macrophages and
Schwann cells release
1954:
758:
Stabenfeldt SE, GarcĂa AJ, LaPlaca MC (June 2006). "Thermoreversible laminin-functionalized hydrogel for neural tissue engineering".
327:, has been identified as an inhibitor of remyelination in the CNS, especially in autoimmune mediated demyelination, such as found in
2131:
2126:
670:
619:
Because of the limited functionality received from autografts, the current gold standard for nerve regeneration and repair, recent
2009:
1608:
Tiangco DA, Papakonstantinou KC, Mullinax KA, Terzis JK (May 2001). "IGF-I and end-to-side nerve repair: a dose-response study".
1423:"Astrocytes and neurons share region-specific transcriptional signatures that confer regional identity to neuronal reprogramming"
283:
335:(MS). Nogo A functions via either its amino-Nogo terminus through an unknown receptor, or by its Nogo-66 terminus through NgR1,
2080:
1369:"Human neuroma contains increased levels of semaphorin 3A, which surrounds nerve fibers and reduces neurite extension in vitro"
435:
574:
across a gap. Nerve segments are taken from another part of the body (the donor site) and inserted into the lesion to provide
1771:
Phillips JB, Bunting SC, Hall SM, Brown RA (2005). "Neural tissue engineering: a self-organizing collagen guidance conduit".
360:
110:, is becoming a rapidly growing field dedicated to the discovery of new ways to recover nerve functionality after injury.
587:
factors within the target muscle itself can also help enhance axon regeneration. Accelerating neuroregeneration and the
92:, which is an attempt at repair. In the CNS, synaptic stripping occurs as glial foot processes invade the dead synapse.
710:
102:
alone affect an estimated 10,000 people each year. As a result of this high incidence of neurological injuries, nerve
1421:
Herrero-Navarro Ă, Puche-Aroca L, Moreno-Juan V, Sempere-FerrĂ ndez A, Espinosa A, SusĂn R, et al. (April 2021).
520:
163:
1066:
Shafqat, Areez; Albalkhi, Ibrahem; Magableh, Hamzah M.; Saleh, Tariq; Alkattan, Khaled; Yaqinuddin, Ahmed (2023).
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target is critically important in order to reduce the possibility of permanent paralysis due to muscular atrophy.
620:
485:
126:
107:
69:
2217:
1367:
Tannemaat MR, Korecka J, Ehlert EM, Mason MR, van Duinen SG, Boer GJ, Malessy MJ, Verhaagen J (December 2007).
447:
2085:
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95:
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2065:
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202:
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103:
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77:
73:
438:) because they share the same lineage as neurons and regionâspecific transcription signatures, while the
2004:
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347:. Antagonising this inhibitor results in improved remyelination, as it is involved in the RhoA pathway.
2174:
2149:
1434:
1188:
1024:
729:
Kandel ER, Schwartz JH, Jessell TM (2003). "Chapter 55: The formation and regeneration of synapses".
641:
528:
413:
409:
207:
99:
1179:
Zhang H, Uchimura K, Kadomatsu K (November 2006). "Brain keratan sulfate and glial scar formation".
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532:
519:
Surgery can be done in case a peripheral nerve has become cut or otherwise divided. This is called
2111:
1832:
1676:
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1212:
1127:"Intrinsic electrical properties of mammalian neurons and CNS function: a historical perspective"
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997:
649:
543:
The expectations after surgical repair of a divided peripheral nerve depends on several factors:
332:
146:
1230:
Song I, Dityatev A (January 2018). "Crosstalk between glia, extracellular matrix and neurons".
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1935:
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1318:"A perspective on the role of class III semaphorin signaling in central nervous system trauma"
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1068:"Tackling the glial scar in spinal cord regeneration: new discoveries and future directions"
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886:
878:
803:
767:
972:
Bradbury EJ, McMahon SB (August 2006). "Spinal cord repair strategies: why do they work?".
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While theses techniques show lot of promise in animal models for many otherwise incurable
305:
1906:"Promotion of Functional Nerve Regeneration by Inhibition of Microtubule Detyrosination"
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1102:
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1028:
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1978:
1930:
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Buffo A, Zagrebelsky M, Huber AB, Skerra A, Schwab ME, Strata P, Rossi F (March 2000).
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41:
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Gobrecht P, Andreadaki A, Diekmann H, Heskamp A, Leibinger M, Fischer D (April 2016).
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are not expressed or re-expressed; for instance, the extracellular matrix is lacking
219:
130:
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1001:
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Proteins of oligodendritic or glial debris origin that influence neuroregeneration:
1946:
1921:
1836:
1385:
1259:
1052:
840:(2006). "Nerve Regeneration: Tissue Engineering Strategies". In Bronzino JD (ed.).
489:
454:
384:(Semaphorin 4D) functions through the PlexinB1 receptor and inhibits remyelination.
177:
142:
134:
31:
1637:
1480:"A Widespread Neurogenic Potential of Neocortical Astrocytes Is Induced by Injury"
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1997:
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17:
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180:. Injury to the peripheral nervous system immediately elicits the migration of
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or cell products. Neuroregenerative mechanisms may include generation of new
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1992:
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Zamboni M, Llorens-Bobadilla E, Magnusson JP, Frisén J (October 2020).
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have also been used against inhibitory factors such as NI-35 and NOGO.
228:
138:
65:
1664:
1416:
1414:
2035:
2019:
1538:
Payne SH (2001). "Nerve repair and grafting in the upper extremity".
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705:
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81:
61:
49:
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is intact, and they have made contact with the
Schwann cells in the
1820:
2014:
524:
462:
162:
113:
The nervous system is divided by neurologists into two parts: the
474:
428:
378:
functions through the EphA4 receptor and inhibits remyelination.
340:
287:
57:
53:
1950:
434:
The most commonly targeted glias are astrocytes (usually using
844:(third ed.). Boca Raton, Fla.: CRC Taylor & Francis.
363:
acts via the receptors NgR2, GT1b, NgR1, p75, TROY and LINGO1.
453:
Targeted genes usually depend on the type of neuron sought; (
644:). These strategies appear promising on animal models with
481:
and self-amplification phase before maturating as neurons.
1732:"IGF-1 gene transfer into denervated rat laryngeal muscle"
477:
can also increase reprograming efficiency by causing a
27:
Renewal or physiological repair of damaged nerve tissue
867:"Intrinsic mechanisms of neuronal axon regeneration"
2185:
2142:
2094:
2056:
2049:
2028:
1985:
1736:Archives of OtolaryngologyâHead & Neck Surgery
730:
1730:Flint PW, Shiotani A, O'Malley BW (March 1999).
1316:Mecollari V, Nieuwenhuis B, Verhaagen J (2014).
1540:Journal of the Southern Orthopaedic Association
760:Journal of Biomedical Materials Research Part A
84:sheath. The proximal segment can either die by
831:
829:
827:
825:
603:Variations on the nerve autograft include the
1962:
1533:
1531:
1529:
1527:
1525:
1523:
1174:
1172:
8:
925:"Glial inhibition of CNS axon regeneration"
737:(fourth ed.). Cambridge: McGraw Hill.
623:research has focused on the development of
353:a non-permissive growth factor from myelin.
2053:
1969:
1955:
1947:
1181:Annals of the New York Academy of Sciences
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948:
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646:experimental autoimmune encephalomyelitis
329:experimental autoimmune encephalomyelitis
68:. Neuroregeneration differs between the
721:
323:âThe protein family Nogo, particularly
1610:Journal of Reconstructive Microsurgery
1567:Journal of Reconstructive Microsurgery
405:in vivo glias to neurons reprogramming
278:In response to scar-inducing factors,
167:GuillainâBarrĂ© syndrome â nerve damage
153:Peripheral nervous system regeneration
98:affect over 90,000 people every year.
473:and elicits a neurogenic program and
7:
842:The biomedical engineering handbook
371:Oligodendrocyte myelin glycoprotein
214:Central nervous system regeneration
40:involves the regrowth or repair of
1869:10.1523/JNEUROSCI.20-06-02275.2000
1322:Frontiers in Cellular Neuroscience
1244:10.1016/j.brainresbull.2017.03.003
1131:Frontiers in Cellular Neuroscience
1072:Frontiers in Cellular Neuroscience
808:10.1016/j.biomaterials.2006.01.053
25:
284:chondroitin sulfate proteoglycans
2010:Lateralization of brain function
865:Mahar M, Cavalli V (June 2018).
446:because some serotypes pass the
274:Chondroitin sulfate proteoglycan
2081:Somatosensory evoked potentials
521:peripheral nerve reconstruction
450:and it does not cause disease.
1922:10.1523/JNEUROSCI.4486-15.2016
1386:10.1523/JNEUROSCI.4571-07.2007
361:Myelin-associated glycoprotein
282:up regulate the production of
1:
299:Keratan sulfate proteoglycans
256:Inhibition of axonal regrowth
974:Nature Reviews. Neuroscience
929:Nature Reviews. Neuroscience
871:Nature Reviews. Neuroscience
733:Principles of neural Science
145:of many diseases, including
137:along with their associated
1910:The Journal of Neuroscience
1856:The Journal of Neuroscience
1373:The Journal of Neuroscience
1125:LlinĂĄs RR (November 2014).
923:Yiu G, He Z (August 2006).
711:Spinal cord injury research
2234:
1749:10.1001/archotol.125.3.274
1709:10.1089/hum.1998.9.14-2039
1496:10.1016/j.stem.2020.07.006
1085:10.3389/fncel.2023.1180825
676:Microtubule detyrosination
500:Neural stem cells grafting
486:neurodegenerative diseases
259:
240:expression, among others.
172:axons is also governed by
156:
106:and repair, a subfield of
29:
2076:Auditory evoked potential
883:10.1038/s41583-018-0001-8
621:neural tissue engineering
599:Allografts and xenografts
569:Autologous nerve grafting
496:have started as of 2023.
127:peripheral nervous system
108:neural tissue engineering
70:peripheral nervous system
1785:10.1089/ten.2005.11.1611
1335:10.3389/fncel.2014.00328
1144:10.3389/fncel.2014.00320
469:...); RBPJ-k blocks the
312:Other inhibitory factors
210:that enhance re-growth.
30:Not to be confused with
2086:Visual evoked potential
1232:Brain Research Bulletin
1201:10.1196/annals.1377.014
628:nerve guidance conduits
535:is almost always used.
159:Peripheral nerve injury
117:(which consists of the
96:Nervous system injuries
2170:Long-term potentiation
2122:Postsynaptic potential
2066:Bereitschaftspotential
1579:10.1055/s-2007-1000208
1447:10.1126/sciadv.abe8978
1287:10.1006/exnr.2002.7884
1275:Experimental Neurology
691:Magnetic nanoparticles
615:Nerve guidance conduit
444:adeno-associated virus
203:Wallerian degeneration
176:factors secreted from
168:
115:central nervous system
90:chromatolytic reaction
78:Wallerian degeneration
74:central nervous system
2005:Intracranial pressure
701:Regenerative medicine
654:Monoclonal antibodies
442:used is typically an
410:Transcription factors
260:Further information:
184:, Schwann cells, and
166:
2175:Long-term depression
2150:Axoplasmic transport
1622:10.1055/s-2001-14516
642:passive immunisation
529:operating microscope
457:is known to produce
208:neurotrophic factors
100:Spinal cord injuries
2165:Synaptic plasticity
2157:/Nerve regeneration
1809:Nature Neuroscience
1439:2021SciA....7.8978H
1193:2006NYASA1086...81Z
1029:1995Natur.378..498B
772:10.1002/jbm.a.30638
555:mechanism of injury
533:surgical tourniquet
448:blood brain barrier
414:activation of genes
400:Neurons replacement
395:Clinical treatments
129:(which consists of
2112:Membrane potential
1977:Physiology of the
1773:Tissue Engineering
1697:Human Gene Therapy
1653:Muscle & Nerve
671:Muscle LIM protein
648:(EAE), a model of
333:multiple sclerosis
293:glycosaminoglycans
169:
147:multiple sclerosis
2205:
2204:
2201:
2200:
2155:Neuroregeneration
2102:Neurotransmission
1665:10.1002/mus.10165
1490:(4): 605â617.e5.
1023:(6556): 498â501.
851:978-0-8493-2123-8
744:978-0-8385-7701-1
576:endoneurial tubes
479:dedifferentiation
418:CRISPR activation
38:Neuroregeneration
16:(Redirected from
2225:
2117:Action potential
2095:Other short term
2058:Evoked potential
2054:
1971:
1964:
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1916:(14): 3890â902.
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1779:(9â10): 1611â7.
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1433:(15): eabe8978.
1427:Science Advances
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1221:
1220:
1176:
1167:
1166:
1156:
1146:
1122:
1116:
1115:
1105:
1087:
1063:
1057:
1056:
1037:10.1038/378498a0
1012:
1006:
1005:
969:
963:
962:
952:
920:
905:
904:
894:
862:
856:
855:
833:
820:
819:
790:
784:
783:
755:
749:
748:
736:
726:
21:
18:Neurorestoration
2233:
2232:
2228:
2227:
2226:
2224:
2223:
2222:
2218:Neurophysiology
2208:
2207:
2206:
2197:
2181:
2161:Neuroplasticity
2138:
2090:
2045:
2024:
1981:
1975:
1945:
1903:
1900:
1898:Further reading
1895:
1849:
1848:
1844:
1805:
1804:
1800:
1770:
1769:
1765:
1729:
1728:
1724:
1703:(14): 2039â47.
1693:
1692:
1688:
1650:
1649:
1645:
1607:
1606:
1602:
1564:
1563:
1559:
1537:
1536:
1521:
1477:
1476:
1472:
1420:
1419:
1412:
1379:(52): 14260â4.
1366:
1365:
1361:
1315:
1314:
1310:
1272:
1271:
1267:
1229:
1228:
1224:
1178:
1177:
1170:
1124:
1123:
1119:
1065:
1064:
1060:
1014:
1013:
1009:
986:10.1038/nrn1964
971:
970:
966:
941:10.1038/nrn1956
922:
921:
908:
864:
863:
859:
852:
838:Mallapragada SK
835:
834:
823:
792:
791:
787:
757:
756:
752:
745:
728:
727:
723:
719:
696:Neuroprotection
662:
637:
617:
601:
571:
562:level of injury
541:
517:
512:
507:
505:Tissue regrowth
502:
494:clinical trials
422:small molecules
407:
402:
397:
314:
306:Keratan sulfate
301:
276:
264:
258:
216:
161:
155:
88:or undergo the
42:nervous tissues
35:
28:
23:
22:
15:
12:
11:
5:
2231:
2229:
2221:
2220:
2210:
2209:
2203:
2202:
2199:
2198:
2196:
2195:
2193:Myelinogenesis
2189:
2187:
2183:
2182:
2180:
2179:
2178:
2177:
2172:
2158:
2152:
2146:
2144:
2140:
2139:
2137:
2136:
2135:
2134:
2129:
2119:
2114:
2109:
2104:
2098:
2096:
2092:
2091:
2089:
2088:
2083:
2078:
2073:
2068:
2062:
2060:
2051:
2047:
2046:
2044:
2043:
2038:
2032:
2030:
2026:
2025:
2023:
2022:
2017:
2012:
2007:
2002:
2001:
2000:
1989:
1987:
1983:
1982:
1979:nervous system
1976:
1974:
1973:
1966:
1959:
1951:
1901:
1899:
1896:
1894:
1893:
1862:(6): 2275â86.
1842:
1821:10.1038/nn1261
1798:
1763:
1722:
1686:
1643:
1600:
1557:
1546:(3): 173â189.
1519:
1484:Cell Stem Cell
1470:
1410:
1359:
1308:
1265:
1222:
1168:
1117:
1058:
1007:
964:
906:
877:(6): 323â337.
857:
850:
821:
802:(19): 3560â9.
785:
750:
743:
720:
718:
715:
714:
713:
708:
703:
698:
693:
688:
686:Magnetic field
683:
681:Myelinogenesis
678:
673:
668:
661:
658:
636:
633:
616:
613:
600:
597:
570:
567:
566:
565:
558:
551:
540:
537:
516:
513:
511:
508:
506:
503:
501:
498:
490:brain injuries
431:into neurons.
406:
403:
401:
398:
396:
393:
392:
391:
385:
379:
373:
364:
354:
348:
313:
310:
300:
297:
275:
272:
257:
254:
225:Growth factors
215:
212:
157:Main article:
154:
151:
72:(PNS) and the
26:
24:
14:
13:
10:
9:
6:
4:
3:
2:
2230:
2219:
2216:
2215:
2213:
2194:
2191:
2190:
2188:
2184:
2176:
2173:
2171:
2168:
2167:
2166:
2162:
2159:
2156:
2153:
2151:
2148:
2147:
2145:
2141:
2133:
2130:
2128:
2125:
2124:
2123:
2120:
2118:
2115:
2113:
2110:
2108:
2105:
2103:
2100:
2099:
2097:
2093:
2087:
2084:
2082:
2079:
2077:
2074:
2072:
2069:
2067:
2064:
2063:
2061:
2059:
2055:
2052:
2048:
2042:
2039:
2037:
2034:
2033:
2031:
2029:Primarily PNS
2027:
2021:
2018:
2016:
2013:
2011:
2008:
2006:
2003:
1999:
1996:
1995:
1994:
1991:
1990:
1988:
1986:Primarily CNS
1984:
1980:
1972:
1967:
1965:
1960:
1958:
1953:
1952:
1949:
1944:
1941:
1937:
1932:
1927:
1923:
1919:
1915:
1911:
1907:
1897:
1889:
1885:
1880:
1875:
1870:
1865:
1861:
1857:
1853:
1846:
1843:
1838:
1834:
1830:
1826:
1822:
1818:
1815:(7): 736â44.
1814:
1810:
1802:
1799:
1794:
1790:
1786:
1782:
1778:
1774:
1767:
1764:
1759:
1755:
1750:
1745:
1741:
1737:
1733:
1726:
1723:
1718:
1714:
1710:
1706:
1702:
1698:
1690:
1687:
1682:
1678:
1674:
1670:
1666:
1662:
1658:
1654:
1647:
1644:
1639:
1635:
1631:
1627:
1623:
1619:
1616:(4): 247â56.
1615:
1611:
1604:
1601:
1596:
1592:
1588:
1584:
1580:
1576:
1573:(7): 459â71.
1572:
1568:
1561:
1558:
1553:
1549:
1545:
1541:
1534:
1532:
1530:
1528:
1526:
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1515:
1511:
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1501:
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1471:
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1411:
1406:
1402:
1397:
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1387:
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1374:
1370:
1363:
1360:
1355:
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1346:
1341:
1336:
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1323:
1319:
1312:
1309:
1304:
1300:
1296:
1292:
1288:
1284:
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1276:
1269:
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1261:
1257:
1253:
1249:
1245:
1241:
1237:
1233:
1226:
1223:
1218:
1214:
1210:
1206:
1202:
1198:
1194:
1190:
1186:
1182:
1175:
1173:
1169:
1164:
1160:
1155:
1150:
1145:
1140:
1136:
1132:
1128:
1121:
1118:
1113:
1109:
1104:
1099:
1095:
1091:
1086:
1081:
1077:
1073:
1069:
1062:
1059:
1054:
1050:
1046:
1042:
1038:
1034:
1030:
1026:
1022:
1018:
1011:
1008:
1003:
999:
995:
991:
987:
983:
980:(8): 644â53.
979:
975:
968:
965:
960:
956:
951:
946:
942:
938:
935:(8): 617â27.
934:
930:
926:
919:
917:
915:
913:
911:
907:
902:
898:
893:
888:
884:
880:
876:
872:
868:
861:
858:
853:
847:
843:
839:
832:
830:
828:
826:
822:
817:
813:
809:
805:
801:
797:
789:
786:
781:
777:
773:
769:
766:(4): 718â25.
765:
761:
754:
751:
746:
740:
735:
734:
725:
722:
716:
712:
709:
707:
704:
702:
699:
697:
694:
692:
689:
687:
684:
682:
679:
677:
674:
672:
669:
667:
664:
663:
659:
657:
655:
651:
647:
643:
634:
632:
629:
626:
625:bioartificial
622:
614:
612:
610:
606:
598:
596:
594:
590:
589:reinnervation
584:
580:
577:
568:
563:
559:
556:
552:
549:
546:
545:
544:
538:
536:
534:
530:
526:
522:
514:
509:
504:
499:
497:
495:
491:
487:
482:
480:
476:
472:
471:Notch pathway
468:
464:
460:
459:glutamatergic
456:
451:
449:
445:
441:
437:
432:
430:
427:
423:
419:
415:
411:
404:
399:
394:
389:
386:
383:
380:
377:
374:
372:
368:
365:
362:
358:
355:
352:
349:
346:
342:
338:
334:
330:
326:
322:
319:
318:
317:
311:
309:
307:
298:
296:
294:
289:
285:
281:
273:
271:
268:
263:
255:
253:
251:
247:
241:
239:
234:
230:
226:
221:
220:extracellular
213:
211:
209:
204:
200:
196:
191:
187:
183:
179:
178:Schwann cells
175:
165:
160:
152:
150:
148:
144:
140:
136:
135:spinal nerves
132:
128:
124:
120:
116:
111:
109:
105:
101:
97:
93:
91:
87:
83:
80:, losing its
79:
75:
71:
67:
63:
59:
55:
51:
47:
43:
39:
33:
19:
2154:
1913:
1909:
1902:
1859:
1855:
1845:
1812:
1808:
1801:
1776:
1772:
1766:
1742:(3): 274â9.
1739:
1735:
1725:
1700:
1696:
1689:
1659:(1): 87â93.
1656:
1652:
1646:
1613:
1609:
1603:
1570:
1566:
1560:
1543:
1539:
1487:
1483:
1473:
1430:
1426:
1376:
1372:
1362:
1325:
1321:
1311:
1281:(1): 61â75.
1278:
1274:
1268:
1235:
1231:
1225:
1187:(1): 81â90.
1184:
1180:
1134:
1130:
1120:
1075:
1071:
1061:
1020:
1016:
1010:
977:
973:
967:
932:
928:
874:
870:
860:
841:
836:Recknor JB,
799:
796:Biomaterials
795:
788:
763:
759:
753:
732:
724:
638:
635:Immunisation
618:
602:
585:
581:
572:
561:
554:
547:
542:
518:
483:
452:
433:
424:are used to
408:
387:
381:
375:
366:
356:
350:
320:
315:
302:
277:
265:
242:
217:
170:
143:pathogenesis
112:
104:regeneration
94:
37:
36:
32:Neurogenesis
1998:Wakefulness
1238:: 101â108.
331:(EAE), and
250:LlinĂĄs' law
233:Glial scars
199:endoneurium
186:macrophages
174:chemotactic
123:spinal cord
2132:Inhibitory
2127:Excitatory
717:References
593:denervated
510:Peripheral
280:astrocytes
267:Glial cell
262:Glial scar
246:glial scar
182:phagocytes
125:) and the
2143:Long term
2107:Chronaxie
2041:Sensation
1094:1662-5102
609:xenograft
605:allograft
539:Prognosis
467:GABAergic
426:reprogram
376:Ephrin B3
223:neurons.
195:cell body
86:apoptosis
2212:Category
1940:27053198
1888:10704503
1829:15184901
1793:16259614
1758:10190798
1681:38261013
1673:12115953
1630:11396586
1595:24168382
1552:12132829
1514:32758425
1465:33827819
1405:18160633
1354:25386118
1303:39940363
1295:12009760
1252:28284900
1217:27885790
1209:17185507
1163:25408634
1112:37293626
1103:10244598
1002:11890502
994:16858392
959:16858390
901:29666508
816:16500703
780:16555267
660:See also
607:and the
229:laminins
66:synapses
1993:Arousal
1931:6705512
1879:6772513
1837:9613584
1717:9759931
1587:9819092
1505:7534841
1456:8026135
1435:Bibcode
1396:6673446
1345:4209881
1328:: 328.
1260:3287589
1189:Bibcode
1154:4219458
1137:: 320.
1053:4352534
1045:7477407
1025:Bibcode
950:2693386
892:5987780
515:Surgery
416:(using
388:Sema 3A
382:Sema 4D
188:to the
139:ganglia
131:cranial
50:neurons
2036:Reflex
2020:Memory
1938:
1928:
1886:
1876:
1835:
1827:
1791:
1756:
1715:
1679:
1671:
1638:528789
1636:
1628:
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1585:
1550:
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1301:
1293:
1258:
1250:
1215:
1207:
1161:
1151:
1110:
1100:
1092:
1051:
1043:
1017:Nature
1000:
992:
957:
947:
899:
889:
848:
814:
778:
741:
706:SPIONs
527:or an
525:loupes
440:vector
345:LINGO1
325:Nogo-A
190:lesion
82:myelin
62:myelin
2186:Other
2015:Sleep
1833:S2CID
1677:S2CID
1634:S2CID
1591:S2CID
1299:S2CID
1256:S2CID
1213:S2CID
1049:S2CID
998:S2CID
591:of a
492:, no
463:ASCL1
429:glias
420:) or
351:NI-35
238:GAP43
119:brain
64:, or
58:axons
46:cells
2071:P300
2050:Both
1936:PMID
1884:PMID
1825:PMID
1789:PMID
1754:PMID
1713:PMID
1669:PMID
1626:PMID
1583:PMID
1548:PMID
1510:PMID
1461:PMID
1401:PMID
1350:PMID
1291:PMID
1248:PMID
1205:PMID
1185:1086
1159:PMID
1108:PMID
1090:ISSN
1041:PMID
990:PMID
955:PMID
897:PMID
846:ISBN
812:PMID
776:PMID
739:ISBN
666:PTEN
560:The
553:The
488:and
475:Sox2
455:NGN2
436:GFAP
367:OMgp
341:TROY
321:NOGO
288:RhoA
133:and
121:and
54:glia
1926:PMC
1918:doi
1874:PMC
1864:doi
1817:doi
1781:doi
1744:doi
1740:125
1705:doi
1661:doi
1618:doi
1575:doi
1500:PMC
1492:doi
1451:PMC
1443:doi
1391:PMC
1381:doi
1340:PMC
1330:doi
1283:doi
1279:175
1240:doi
1236:136
1197:doi
1149:PMC
1139:doi
1098:PMC
1080:doi
1033:doi
1021:378
982:doi
945:PMC
937:doi
887:PMC
879:doi
804:doi
768:doi
652:.
548:Age
357:MAG
343:or
337:p75
252:).
2214::
1934:.
1924:.
1914:36
1912:.
1908:.
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1858:.
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