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Abnormal reaction to central nervous system injury in mice lacking glial fibrillary acidic protein and vimentin.

Pekny M, Johansson CB, Eliasson C, Stakeberg J, Wallén A, Perlmann T, Lendahl U, Betsholtz C, Berthold CH, Frisén J - J. Cell Biol. (1999)

Bottom Line: In response to injury of the central nervous system, astrocytes become reactive and express high levels of the intermediate filament (IF) proteins glial fibrillary acidic protein (GFAP), vimentin, and nestin.Glial scar formation appeared normal after spinal cord or brain lesions in GFAP-/- or vimentin-/- mice, but was impaired in GFAP-/-vim-/- mice that developed less dense scars frequently accompanied by bleeding.These results show that GFAP and vimentin are required for proper glial scar formation in the injured central nervous system and that some degree of functional overlap exists between these IF proteins.

View Article: PubMed Central - PubMed

Affiliation: Department of Medical Biochemistry, Gothenburg University, SE-405 30 Gothenburg, Sweden. milos.pekny@medkem.gu.se

ABSTRACT
In response to injury of the central nervous system, astrocytes become reactive and express high levels of the intermediate filament (IF) proteins glial fibrillary acidic protein (GFAP), vimentin, and nestin. We have shown that astrocytes in mice deficient for both GFAP and vimentin (GFAP-/-vim-/-) cannot form IFs even when nestin is expressed and are thus devoid of IFs in their reactive state. Here, we have studied the reaction to injury in the central nervous system in GFAP-/-, vimentin-/-, or GFAP-/-vim-/- mice. Glial scar formation appeared normal after spinal cord or brain lesions in GFAP-/- or vimentin-/- mice, but was impaired in GFAP-/-vim-/- mice that developed less dense scars frequently accompanied by bleeding. These results show that GFAP and vimentin are required for proper glial scar formation in the injured central nervous system and that some degree of functional overlap exists between these IF proteins.

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Blood vessel dilation. Hematoxylin and eosin stained  coronal brain sections from wild-type (A) and GFAP−/−vim−/−  (B) mice show an increased number of large diameter blood vessels in GFAP−/−vim−/− mice (some are indicated by arrowheads in B). The lumen of the lateral ventricle is indicated with  an asterisk and the corpus callosum is labeled cc. Bar, 500 μm.
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Figure 1: Blood vessel dilation. Hematoxylin and eosin stained coronal brain sections from wild-type (A) and GFAP−/−vim−/− (B) mice show an increased number of large diameter blood vessels in GFAP−/−vim−/− mice (some are indicated by arrowheads in B). The lumen of the lateral ventricle is indicated with an asterisk and the corpus callosum is labeled cc. Bar, 500 μm.

Mentions: We first analyzed the uninjured nervous system of the mutant mice. Many blood vessels appeared dilated in the brain and spinal cord of GFAP−/−vim−/− mice (Fig. 1). The lumina of these structures were lined with von Willebrand factor–immunoreactive endothelial cells indicating that they were true blood vessels rather than, for example, cavities formed by degeneration (data not shown). Measurements of blood vessel diameters in these mice revealed an almost threefold increase in the number of blood vessels with a diameter >15 μm compared to wild-type mice (P < 0.0005; Fig. 2 A). We frequently noticed that there was an unusually deep indentation in the tissue of the dorsal spinal cord in many of the mutant mice. In wild-type mice, there is often an invagination below the dorsal spinal vein, but measurements of the depth of the invagination revealed a statistically significant increase in the depth compared to wild-type mice in GFAP−/− (P < 0.005), vimentin−/− (P < 0.0001), and GFAP−/−vim−/− mice (P < 0.0001; Figs. 2 B and 6, A–D).


Abnormal reaction to central nervous system injury in mice lacking glial fibrillary acidic protein and vimentin.

Pekny M, Johansson CB, Eliasson C, Stakeberg J, Wallén A, Perlmann T, Lendahl U, Betsholtz C, Berthold CH, Frisén J - J. Cell Biol. (1999)

Blood vessel dilation. Hematoxylin and eosin stained  coronal brain sections from wild-type (A) and GFAP−/−vim−/−  (B) mice show an increased number of large diameter blood vessels in GFAP−/−vim−/− mice (some are indicated by arrowheads in B). The lumen of the lateral ventricle is indicated with  an asterisk and the corpus callosum is labeled cc. Bar, 500 μm.
© Copyright Policy
Related In: Results  -  Collection

Show All Figures
getmorefigures.php?uid=PMC2185074&req=5

Figure 1: Blood vessel dilation. Hematoxylin and eosin stained coronal brain sections from wild-type (A) and GFAP−/−vim−/− (B) mice show an increased number of large diameter blood vessels in GFAP−/−vim−/− mice (some are indicated by arrowheads in B). The lumen of the lateral ventricle is indicated with an asterisk and the corpus callosum is labeled cc. Bar, 500 μm.
Mentions: We first analyzed the uninjured nervous system of the mutant mice. Many blood vessels appeared dilated in the brain and spinal cord of GFAP−/−vim−/− mice (Fig. 1). The lumina of these structures were lined with von Willebrand factor–immunoreactive endothelial cells indicating that they were true blood vessels rather than, for example, cavities formed by degeneration (data not shown). Measurements of blood vessel diameters in these mice revealed an almost threefold increase in the number of blood vessels with a diameter >15 μm compared to wild-type mice (P < 0.0005; Fig. 2 A). We frequently noticed that there was an unusually deep indentation in the tissue of the dorsal spinal cord in many of the mutant mice. In wild-type mice, there is often an invagination below the dorsal spinal vein, but measurements of the depth of the invagination revealed a statistically significant increase in the depth compared to wild-type mice in GFAP−/− (P < 0.005), vimentin−/− (P < 0.0001), and GFAP−/−vim−/− mice (P < 0.0001; Figs. 2 B and 6, A–D).

Bottom Line: In response to injury of the central nervous system, astrocytes become reactive and express high levels of the intermediate filament (IF) proteins glial fibrillary acidic protein (GFAP), vimentin, and nestin.Glial scar formation appeared normal after spinal cord or brain lesions in GFAP-/- or vimentin-/- mice, but was impaired in GFAP-/-vim-/- mice that developed less dense scars frequently accompanied by bleeding.These results show that GFAP and vimentin are required for proper glial scar formation in the injured central nervous system and that some degree of functional overlap exists between these IF proteins.

View Article: PubMed Central - PubMed

Affiliation: Department of Medical Biochemistry, Gothenburg University, SE-405 30 Gothenburg, Sweden. milos.pekny@medkem.gu.se

ABSTRACT
In response to injury of the central nervous system, astrocytes become reactive and express high levels of the intermediate filament (IF) proteins glial fibrillary acidic protein (GFAP), vimentin, and nestin. We have shown that astrocytes in mice deficient for both GFAP and vimentin (GFAP-/-vim-/-) cannot form IFs even when nestin is expressed and are thus devoid of IFs in their reactive state. Here, we have studied the reaction to injury in the central nervous system in GFAP-/-, vimentin-/-, or GFAP-/-vim-/- mice. Glial scar formation appeared normal after spinal cord or brain lesions in GFAP-/- or vimentin-/- mice, but was impaired in GFAP-/-vim-/- mice that developed less dense scars frequently accompanied by bleeding. These results show that GFAP and vimentin are required for proper glial scar formation in the injured central nervous system and that some degree of functional overlap exists between these IF proteins.

Show MeSH
Related in: MedlinePlus