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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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Response to cortical injury in wild-type and mutant mice. Hematoxylin and erythrosin staining and nestin-IR in adjacent sections of frontal cortex from mice 3 d or 3 wk after a fine needle cortical injury. In most of GFAP−/−vim−/− mice 3 d after the injury,  bleeding was detected within the lesion zone (D). Nestin-immunoreactive cells can be seen in the lesion area in all animals 3 d after the  injury, but the labeling appears weaker and more diffuse in the cells of vimentin−/− and GFAP−/−vim−/− mice (G and H). The injury was sealed in animals of all genotypes 3 wk after this type of injury (I–L). Bar, 100 μm.
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Figure 8: Response to cortical injury in wild-type and mutant mice. Hematoxylin and erythrosin staining and nestin-IR in adjacent sections of frontal cortex from mice 3 d or 3 wk after a fine needle cortical injury. In most of GFAP−/−vim−/− mice 3 d after the injury, bleeding was detected within the lesion zone (D). Nestin-immunoreactive cells can be seen in the lesion area in all animals 3 d after the injury, but the labeling appears weaker and more diffuse in the cells of vimentin−/− and GFAP−/−vim−/− mice (G and H). The injury was sealed in animals of all genotypes 3 wk after this type of injury (I–L). Bar, 100 μm.

Mentions: Glial scar formation was also analyzed in the brain. A cortical stab wound was done with a fine needle, resulting in a much more restricted injury than the spinal cord lesion. Interestingly, 3 out of 11 GFAP−/−vim−/− mice died shortly after the injury and the necropsy showed extensive intracranial bleeding that was interpreted as the cause of death (data not shown). In the group of GFAP−/−vim−/− mice that were killed 3 d after the injury, 3 out of 5 mice showed extensive bleeding at the site of injury (Fig. 8 D). Bleeding of comparable magnitude was not seen in mice of other genotypes. In all wild-type, GFAP−/− and vimentin−/− mice, as well as in the GFAP−/−vim−/− mice that survived the operation, the discrete injury caused by the needle did not cause any apparent clinical symptoms and was sealed within 3 wk (Fig. 8). Nestin-IR was detected around the cortical lesion 3 d after the injury in mice of all genotypes (Fig. 8). However, whereas nestin-IR was comparably strong and revealed distinct reactive astrocytes in both wild-type and GFAP−/− mice, it was weaker and diffuse in vimentin−/− and GFAP−/−vim−/− mice (Fig. 8, G and H). Nestin-IR was reduced to undetectable levels after 3 wk in mice of all genotypes (data not shown).


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)

Response to cortical injury in wild-type and mutant mice. Hematoxylin and erythrosin staining and nestin-IR in adjacent sections of frontal cortex from mice 3 d or 3 wk after a fine needle cortical injury. In most of GFAP−/−vim−/− mice 3 d after the injury,  bleeding was detected within the lesion zone (D). Nestin-immunoreactive cells can be seen in the lesion area in all animals 3 d after the  injury, but the labeling appears weaker and more diffuse in the cells of vimentin−/− and GFAP−/−vim−/− mice (G and H). The injury was sealed in animals of all genotypes 3 wk after this type of injury (I–L). Bar, 100 μm.
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Related In: Results  -  Collection

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Figure 8: Response to cortical injury in wild-type and mutant mice. Hematoxylin and erythrosin staining and nestin-IR in adjacent sections of frontal cortex from mice 3 d or 3 wk after a fine needle cortical injury. In most of GFAP−/−vim−/− mice 3 d after the injury, bleeding was detected within the lesion zone (D). Nestin-immunoreactive cells can be seen in the lesion area in all animals 3 d after the injury, but the labeling appears weaker and more diffuse in the cells of vimentin−/− and GFAP−/−vim−/− mice (G and H). The injury was sealed in animals of all genotypes 3 wk after this type of injury (I–L). Bar, 100 μm.
Mentions: Glial scar formation was also analyzed in the brain. A cortical stab wound was done with a fine needle, resulting in a much more restricted injury than the spinal cord lesion. Interestingly, 3 out of 11 GFAP−/−vim−/− mice died shortly after the injury and the necropsy showed extensive intracranial bleeding that was interpreted as the cause of death (data not shown). In the group of GFAP−/−vim−/− mice that were killed 3 d after the injury, 3 out of 5 mice showed extensive bleeding at the site of injury (Fig. 8 D). Bleeding of comparable magnitude was not seen in mice of other genotypes. In all wild-type, GFAP−/− and vimentin−/− mice, as well as in the GFAP−/−vim−/− mice that survived the operation, the discrete injury caused by the needle did not cause any apparent clinical symptoms and was sealed within 3 wk (Fig. 8). Nestin-IR was detected around the cortical lesion 3 d after the injury in mice of all genotypes (Fig. 8). However, whereas nestin-IR was comparably strong and revealed distinct reactive astrocytes in both wild-type and GFAP−/− mice, it was weaker and diffuse in vimentin−/− and GFAP−/−vim−/− mice (Fig. 8, G and H). Nestin-IR was reduced to undetectable levels after 3 wk in mice of all genotypes (data not shown).

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