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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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Ultrastructural  analysis of a cortical stab  wound. Electron micrographs of the frontal cerebral  cortex 3 d after the injury.  The pictures show the border  zone between the spongy tissue of the wounded area and  the surrounding compact  cortical tissue. In wild-type  (A), GFAP−/− (B), or  vimentin−/− (C) mice, the  extracellular space (small asterisk) is restricted and free  of debris. In GFAP−/−  vim−/− mice the extracellular space is filled with masses  of filamentous and diffuse  debris (large asterisk). A, astrocytic profile; M, myelinated axon; S, synaptosome-like profile. Bar, 1 μm.
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Figure 9: Ultrastructural analysis of a cortical stab wound. Electron micrographs of the frontal cerebral cortex 3 d after the injury. The pictures show the border zone between the spongy tissue of the wounded area and the surrounding compact cortical tissue. In wild-type (A), GFAP−/− (B), or vimentin−/− (C) mice, the extracellular space (small asterisk) is restricted and free of debris. In GFAP−/− vim−/− mice the extracellular space is filled with masses of filamentous and diffuse debris (large asterisk). A, astrocytic profile; M, myelinated axon; S, synaptosome-like profile. Bar, 1 μm.

Mentions: To further characterize scar formation in the mutant mice, we analyzed the zone immediately adjacent to the central necrotic area of cortical injury by electron microscopy. This area was similar in wild-type, GFAP−/−, or vimentin−/− mice, but differed in GFAP−/−vim−/− mice. The difference was most apparent in the border zone between the severely disarranged tissue close to the wound and the more distant, compact and normal looking brain tissue. Here, the GFAP−/−vim−/− mice exhibited fragmented tissue with a high accumulation of extracellular debris. This debris was diffuse, finely granular or filamentous of moderate electron density (Fig. 9 d). This was in contrast to mice of the other genotypes (Fig. 9, a–c) in which the brain tissue in the corresponding area showed easily identifiable components (e.g., myelinated and unmyelinated axons, synaptosome-like profiles), narrow extracellular spaces and virtually no extracellular debris.


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)

Ultrastructural  analysis of a cortical stab  wound. Electron micrographs of the frontal cerebral  cortex 3 d after the injury.  The pictures show the border  zone between the spongy tissue of the wounded area and  the surrounding compact  cortical tissue. In wild-type  (A), GFAP−/− (B), or  vimentin−/− (C) mice, the  extracellular space (small asterisk) is restricted and free  of debris. In GFAP−/−  vim−/− mice the extracellular space is filled with masses  of filamentous and diffuse  debris (large asterisk). A, astrocytic profile; M, myelinated axon; S, synaptosome-like profile. Bar, 1 μm.
© Copyright Policy
Related In: Results  -  Collection

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

Figure 9: Ultrastructural analysis of a cortical stab wound. Electron micrographs of the frontal cerebral cortex 3 d after the injury. The pictures show the border zone between the spongy tissue of the wounded area and the surrounding compact cortical tissue. In wild-type (A), GFAP−/− (B), or vimentin−/− (C) mice, the extracellular space (small asterisk) is restricted and free of debris. In GFAP−/− vim−/− mice the extracellular space is filled with masses of filamentous and diffuse debris (large asterisk). A, astrocytic profile; M, myelinated axon; S, synaptosome-like profile. Bar, 1 μm.
Mentions: To further characterize scar formation in the mutant mice, we analyzed the zone immediately adjacent to the central necrotic area of cortical injury by electron microscopy. This area was similar in wild-type, GFAP−/−, or vimentin−/− mice, but differed in GFAP−/−vim−/− mice. The difference was most apparent in the border zone between the severely disarranged tissue close to the wound and the more distant, compact and normal looking brain tissue. Here, the GFAP−/−vim−/− mice exhibited fragmented tissue with a high accumulation of extracellular debris. This debris was diffuse, finely granular or filamentous of moderate electron density (Fig. 9 d). This was in contrast to mice of the other genotypes (Fig. 9, a–c) in which the brain tissue in the corresponding area showed easily identifiable components (e.g., myelinated and unmyelinated axons, synaptosome-like profiles), narrow extracellular spaces and virtually no extracellular debris.

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