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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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Schematic drawings represent the process of the lesion scar formation in the mouse brain. One day after traumatic CNS injury, the BBB is disrupted and macrophages infiltrated the BBB-free area. a Upregulation of GFAP immunoreactivity in reactive astrocytes is already observed. b Three days after the injury, reactive astrocytes significantly increase around the lesion site, but they are absent from the lesion center where the BBB is destroyed. Fibroblasts intrude from the damaged meninges to the lesion site. c By 1 week after injury, fibroblasts actively proliferate and secrete ECMs to form the fibrotic scar. Reactive astrocytes re-occupy the surrounding area of the lesion site and BBB-free area around the lesion site is eliminated. d At 2 weeks after, processes of reactive astrocytes seal the lesion site to form a glia limitans
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Fig1: Schematic drawings represent the process of the lesion scar formation in the mouse brain. One day after traumatic CNS injury, the BBB is disrupted and macrophages infiltrated the BBB-free area. a Upregulation of GFAP immunoreactivity in reactive astrocytes is already observed. b Three days after the injury, reactive astrocytes significantly increase around the lesion site, but they are absent from the lesion center where the BBB is destroyed. Fibroblasts intrude from the damaged meninges to the lesion site. c By 1 week after injury, fibroblasts actively proliferate and secrete ECMs to form the fibrotic scar. Reactive astrocytes re-occupy the surrounding area of the lesion site and BBB-free area around the lesion site is eliminated. d At 2 weeks after, processes of reactive astrocytes seal the lesion site to form a glia limitans

Mentions: The molecular changes in the glial and fibrotic scar are closely related with the tissue repair process of the CNS lesion site. Following CNS injury, bleeding occurs and the BBB is broken down. The infiltration of blood proteins such as thrombin (Nishino et al. 1993) and fibrinogen (Ryu et al. 2009) triggers the inflammatory reaction. At the same time, hematogenous cells including leukocytes, macrophages and lymphocytes also invade from the lesion site to the surrounding neural tissue and secrete various cytokines and chemokines (Donnelly and Popovich 2008; Merrill and Benveniste 1996). Under the influence of these factors, astrocytes, microglia and oligodendrocyte progenitor cells are activated and constitute the glial scar around the lesion site. On the other hand, from several days after injury, fibroblasts intrude from the damaged meninges to the lesion site, proliferate and secrete extracellular matrix molecules (ECMs) including type IV collagen (Type IV collagen), fibronectin and laminin to form the fibrotic scar (Fig. 1). The composition and arrangements of cells in these lesion scars are postulated to play important roles for the protection of damaged tissue, re-establishment of the BBB and isolation of the lesion site from the surrounding neural tissue (Berry et al. 1983; Mathewson and Berry 1985; Maxwell et al. 1990a; for review, see Shearer and Fawcett 2001). Simultaneously, the cells of these scars express the above-mentioned axonal growth-inhibiting molecules, which are believed to prevent the axonal regeneration and functional recovery in the injured CNS.Fig. 1


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)

Schematic drawings represent the process of the lesion scar formation in the mouse brain. One day after traumatic CNS injury, the BBB is disrupted and macrophages infiltrated the BBB-free area. a Upregulation of GFAP immunoreactivity in reactive astrocytes is already observed. b Three days after the injury, reactive astrocytes significantly increase around the lesion site, but they are absent from the lesion center where the BBB is destroyed. Fibroblasts intrude from the damaged meninges to the lesion site. c By 1 week after injury, fibroblasts actively proliferate and secrete ECMs to form the fibrotic scar. Reactive astrocytes re-occupy the surrounding area of the lesion site and BBB-free area around the lesion site is eliminated. d At 2 weeks after, processes of reactive astrocytes seal the lesion site to form a glia limitans
© Copyright Policy
Related In: Results  -  Collection

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

Fig1: Schematic drawings represent the process of the lesion scar formation in the mouse brain. One day after traumatic CNS injury, the BBB is disrupted and macrophages infiltrated the BBB-free area. a Upregulation of GFAP immunoreactivity in reactive astrocytes is already observed. b Three days after the injury, reactive astrocytes significantly increase around the lesion site, but they are absent from the lesion center where the BBB is destroyed. Fibroblasts intrude from the damaged meninges to the lesion site. c By 1 week after injury, fibroblasts actively proliferate and secrete ECMs to form the fibrotic scar. Reactive astrocytes re-occupy the surrounding area of the lesion site and BBB-free area around the lesion site is eliminated. d At 2 weeks after, processes of reactive astrocytes seal the lesion site to form a glia limitans
Mentions: The molecular changes in the glial and fibrotic scar are closely related with the tissue repair process of the CNS lesion site. Following CNS injury, bleeding occurs and the BBB is broken down. The infiltration of blood proteins such as thrombin (Nishino et al. 1993) and fibrinogen (Ryu et al. 2009) triggers the inflammatory reaction. At the same time, hematogenous cells including leukocytes, macrophages and lymphocytes also invade from the lesion site to the surrounding neural tissue and secrete various cytokines and chemokines (Donnelly and Popovich 2008; Merrill and Benveniste 1996). Under the influence of these factors, astrocytes, microglia and oligodendrocyte progenitor cells are activated and constitute the glial scar around the lesion site. On the other hand, from several days after injury, fibroblasts intrude from the damaged meninges to the lesion site, proliferate and secrete extracellular matrix molecules (ECMs) including type IV collagen (Type IV collagen), fibronectin and laminin to form the fibrotic scar (Fig. 1). The composition and arrangements of cells in these lesion scars are postulated to play important roles for the protection of damaged tissue, re-establishment of the BBB and isolation of the lesion site from the surrounding neural tissue (Berry et al. 1983; Mathewson and Berry 1985; Maxwell et al. 1990a; for review, see Shearer and Fawcett 2001). Simultaneously, the cells of these scars express the above-mentioned axonal growth-inhibiting molecules, which are believed to prevent the axonal regeneration and functional recovery in the injured CNS.Fig. 1

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