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Role of the lesion scar in the response to damage and repair of the central nervous system.

Kawano H, Kimura-Kuroda J, Komuta Y, Yoshioka N, Li HP, Kawamura K, Li Y, Raisman G - Cell Tissue Res. (2012)

Bottom Line: At the interface, the reactive astrocytes and the fibroblasts interact to form an organized tissue, the glia limitans.While much attention has been paid to the inhibitory effects of the astrocytic component of the scars on axon regeneration, this review will cover a number of recent studies in which manipulations of the fibroblastic component of the scar by reagents, such as blockers of collagen synthesis have been found to be beneficial for axon regeneration.To what extent these changes in the fibroblasts act via subsequent downstream actions on the astrocytes remains for future investigation.

View Article: PubMed Central - PubMed

Affiliation: Laboratory of Neural Regeneration, Tokyo Metropolitan Institute of Medical Science, Setagaya City, Tokyo 156-8506, Japan. kawano-ht@igakuken.or.jp

ABSTRACT
Traumatic damage to the central nervous system (CNS) destroys the blood-brain barrier (BBB) and provokes the invasion of hematogenous cells into the neural tissue. Invading leukocytes, macrophages and lymphocytes secrete various cytokines that induce an inflammatory reaction in the injured CNS and result in local neural degeneration, formation of a cystic cavity and activation of glial cells around the lesion site. As a consequence of these processes, two types of scarring tissue are formed in the lesion site. One is a glial scar that consists in reactive astrocytes, reactive microglia and glial precursor cells. The other is a fibrotic scar formed by fibroblasts, which have invaded the lesion site from adjacent meningeal and perivascular cells. At the interface, the reactive astrocytes and the fibroblasts interact to form an organized tissue, the glia limitans. The astrocytic reaction has a protective role by reconstituting the BBB, preventing neuronal degeneration and limiting the spread of damage. While much attention has been paid to the inhibitory effects of the astrocytic component of the scars on axon regeneration, this review will cover a number of recent studies in which manipulations of the fibroblastic component of the scar by reagents, such as blockers of collagen synthesis have been found to be beneficial for axon regeneration. To what extent these changes in the fibroblasts act via subsequent downstream actions on the astrocytes remains for future investigation.

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Elimination of the fibrotic scar in the mouse and rat brain has been shown to promote axonal regeneration in a variety of animal models. a In injured brain, axons stop at the border of the fibrotic scar and do not regenerate. b In neonatal and DPY-treated animals, axons regenerate despite of the presence of glial scar and chondroitin sulfate proteoglycan (CSPG) (Stichel et al. 1999a; Kawano et al. 2005). c In the hypothalamic arcuate nucleus (ARC) and by chondroitinase ABC (ChABC) treatment, upregulation of chondroitin sulfate is prevented and axons regenerate (Homma et al. 2006; Li et al. 2007). d In olfactory ensheathing cell (OEC)-transplanted rats, fibrotic scar is not formed and axons regenerate (Teng et al. 2008)
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Fig2: Elimination of the fibrotic scar in the mouse and rat brain has been shown to promote axonal regeneration in a variety of animal models. a In injured brain, axons stop at the border of the fibrotic scar and do not regenerate. b In neonatal and DPY-treated animals, axons regenerate despite of the presence of glial scar and chondroitin sulfate proteoglycan (CSPG) (Stichel et al. 1999a; Kawano et al. 2005). c In the hypothalamic arcuate nucleus (ARC) and by chondroitinase ABC (ChABC) treatment, upregulation of chondroitin sulfate is prevented and axons regenerate (Homma et al. 2006; Li et al. 2007). d In olfactory ensheathing cell (OEC)-transplanted rats, fibrotic scar is not formed and axons regenerate (Teng et al. 2008)

Mentions: There are reports that transected axons stop at the border of the fibrotic scar (Fig. 2a; Camand et al. 2004; Stichel and Müller 1994) and fibroblasts have been shown to express various axonal growth-inhibitory molecules including NG2 proteoglycan (Tang et al. 2003), phosphacan (Tang et al. 2003), tenascin-C (Tang et al. 2003), semaphorin 3A (Pasterkamp et al. 1999) and EphB2 (Bundesen et al. 2003). However, since the CNS tissue is rapidly walled off by astrocytes, the ability of the fibrotic scar to present either a physical or molecular obstacle to the regeneration of severed axons depends upon the extent to which the axons come into contact with it.Fig. 2


Role of the lesion scar in the response to damage and repair of the central nervous system.

Kawano H, Kimura-Kuroda J, Komuta Y, Yoshioka N, Li HP, Kawamura K, Li Y, Raisman G - Cell Tissue Res. (2012)

Elimination of the fibrotic scar in the mouse and rat brain has been shown to promote axonal regeneration in a variety of animal models. a In injured brain, axons stop at the border of the fibrotic scar and do not regenerate. b In neonatal and DPY-treated animals, axons regenerate despite of the presence of glial scar and chondroitin sulfate proteoglycan (CSPG) (Stichel et al. 1999a; Kawano et al. 2005). c In the hypothalamic arcuate nucleus (ARC) and by chondroitinase ABC (ChABC) treatment, upregulation of chondroitin sulfate is prevented and axons regenerate (Homma et al. 2006; Li et al. 2007). d In olfactory ensheathing cell (OEC)-transplanted rats, fibrotic scar is not formed and axons regenerate (Teng et al. 2008)
© Copyright Policy
Related In: Results  -  Collection

Show All Figures
getmorefigures.php?uid=PMC3375417&req=5

Fig2: Elimination of the fibrotic scar in the mouse and rat brain has been shown to promote axonal regeneration in a variety of animal models. a In injured brain, axons stop at the border of the fibrotic scar and do not regenerate. b In neonatal and DPY-treated animals, axons regenerate despite of the presence of glial scar and chondroitin sulfate proteoglycan (CSPG) (Stichel et al. 1999a; Kawano et al. 2005). c In the hypothalamic arcuate nucleus (ARC) and by chondroitinase ABC (ChABC) treatment, upregulation of chondroitin sulfate is prevented and axons regenerate (Homma et al. 2006; Li et al. 2007). d In olfactory ensheathing cell (OEC)-transplanted rats, fibrotic scar is not formed and axons regenerate (Teng et al. 2008)
Mentions: There are reports that transected axons stop at the border of the fibrotic scar (Fig. 2a; Camand et al. 2004; Stichel and Müller 1994) and fibroblasts have been shown to express various axonal growth-inhibitory molecules including NG2 proteoglycan (Tang et al. 2003), phosphacan (Tang et al. 2003), tenascin-C (Tang et al. 2003), semaphorin 3A (Pasterkamp et al. 1999) and EphB2 (Bundesen et al. 2003). However, since the CNS tissue is rapidly walled off by astrocytes, the ability of the fibrotic scar to present either a physical or molecular obstacle to the regeneration of severed axons depends upon the extent to which the axons come into contact with it.Fig. 2

Bottom Line: At the interface, the reactive astrocytes and the fibroblasts interact to form an organized tissue, the glia limitans.While much attention has been paid to the inhibitory effects of the astrocytic component of the scars on axon regeneration, this review will cover a number of recent studies in which manipulations of the fibroblastic component of the scar by reagents, such as blockers of collagen synthesis have been found to be beneficial for axon regeneration.To what extent these changes in the fibroblasts act via subsequent downstream actions on the astrocytes remains for future investigation.

View Article: PubMed Central - PubMed

Affiliation: Laboratory of Neural Regeneration, Tokyo Metropolitan Institute of Medical Science, Setagaya City, Tokyo 156-8506, Japan. kawano-ht@igakuken.or.jp

ABSTRACT
Traumatic damage to the central nervous system (CNS) destroys the blood-brain barrier (BBB) and provokes the invasion of hematogenous cells into the neural tissue. Invading leukocytes, macrophages and lymphocytes secrete various cytokines that induce an inflammatory reaction in the injured CNS and result in local neural degeneration, formation of a cystic cavity and activation of glial cells around the lesion site. As a consequence of these processes, two types of scarring tissue are formed in the lesion site. One is a glial scar that consists in reactive astrocytes, reactive microglia and glial precursor cells. The other is a fibrotic scar formed by fibroblasts, which have invaded the lesion site from adjacent meningeal and perivascular cells. At the interface, the reactive astrocytes and the fibroblasts interact to form an organized tissue, the glia limitans. The astrocytic reaction has a protective role by reconstituting the BBB, preventing neuronal degeneration and limiting the spread of damage. While much attention has been paid to the inhibitory effects of the astrocytic component of the scars on axon regeneration, this review will cover a number of recent studies in which manipulations of the fibroblastic component of the scar by reagents, such as blockers of collagen synthesis have been found to be beneficial for axon regeneration. To what extent these changes in the fibroblasts act via subsequent downstream actions on the astrocytes remains for future investigation.

Show MeSH
Related in: MedlinePlus