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Regeneration beyond the glial scar

Regeneration beyond the glial scar With a few exceptions, severed axons within long myelinated tracts of the central nervous system (CNS) are capable only of abortive sprouting that provides little functional recovery. Injury to the CNS induces tissue damage that creates barriers to regeneration, and one of the main barriers is the glial scar, which consists predominately of reactive astrocytes and proteoglycans. In addition to preventing regeneration, the glial scar might provide several important beneficial functions for stabilizing fragile CNS tissue after injury. After injury, the subpopulation of reactive astrocytes that undergo mitosis immediately surrounding the core of the lesion seems to repair the blood–brain barrier, prevent an overwhelming inflammatory response and limit cellular degeneration. When regenerating axons encounter the environment of the glial scar, so-called dystrophic endbulbs form. For many years, these unusually shaped endbulbs were considered to be sterile, and therefore incapable of extending a growth cone, but more recent research has indicated that axons with dystrophic endings can in fact return to active growth states. In addition to growth-promoting molecules, astrocytes produce four classes of proteoglycan; heparan sulphate proteoglycan, dermatan sulphate proteoglycan, keratan sulphate proteoglycan and chondroitin sulphate proteoglycan (CSPG). Evidence that CSPGs might have a role in the failure of regeneration in the CNS after injury began to emerge in the early 1990s. In addition to the inhibitory effects of CSPGs, several other molecules are now known to be upregulated in the core of the lesion and to contribute to the growth-retarding effects of the glial scar. These include semaphorin 3, ephrin-B2 and its receptor EPHB2, and the Slit proteins. To overcome the inhibitory environment of the glial scar, treatments should ideally provide a growth supportive highway across the lesion cavity, intrinsically enhance the ability of neurons to elongate and manipulate the extrinsic inhibitors that block growth in the immediate environment of the scar. http://www.deepdyve.com/assets/images/DeepDyve-Logo-lg.png Nature Reviews Neuroscience Springer Journals

Regeneration beyond the glial scar

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References (156)

Publisher
Springer Journals
Copyright
Copyright © 2004 by Nature Publishing Group
Subject
Biomedicine; Biomedicine, general; Neurosciences; Behavioral Sciences; Biological Techniques; Neurobiology; Animal Genetics and Genomics
ISSN
1471-003X
eISSN
1471-0048
DOI
10.1038/nrn1326
Publisher site
See Article on Publisher Site

Abstract

With a few exceptions, severed axons within long myelinated tracts of the central nervous system (CNS) are capable only of abortive sprouting that provides little functional recovery. Injury to the CNS induces tissue damage that creates barriers to regeneration, and one of the main barriers is the glial scar, which consists predominately of reactive astrocytes and proteoglycans. In addition to preventing regeneration, the glial scar might provide several important beneficial functions for stabilizing fragile CNS tissue after injury. After injury, the subpopulation of reactive astrocytes that undergo mitosis immediately surrounding the core of the lesion seems to repair the blood–brain barrier, prevent an overwhelming inflammatory response and limit cellular degeneration. When regenerating axons encounter the environment of the glial scar, so-called dystrophic endbulbs form. For many years, these unusually shaped endbulbs were considered to be sterile, and therefore incapable of extending a growth cone, but more recent research has indicated that axons with dystrophic endings can in fact return to active growth states. In addition to growth-promoting molecules, astrocytes produce four classes of proteoglycan; heparan sulphate proteoglycan, dermatan sulphate proteoglycan, keratan sulphate proteoglycan and chondroitin sulphate proteoglycan (CSPG). Evidence that CSPGs might have a role in the failure of regeneration in the CNS after injury began to emerge in the early 1990s. In addition to the inhibitory effects of CSPGs, several other molecules are now known to be upregulated in the core of the lesion and to contribute to the growth-retarding effects of the glial scar. These include semaphorin 3, ephrin-B2 and its receptor EPHB2, and the Slit proteins. To overcome the inhibitory environment of the glial scar, treatments should ideally provide a growth supportive highway across the lesion cavity, intrinsically enhance the ability of neurons to elongate and manipulate the extrinsic inhibitors that block growth in the immediate environment of the scar.

Journal

Nature Reviews NeuroscienceSpringer Journals

Published: Feb 1, 2004

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