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Daniel Sun, Ming Lye-Barthel, Richard H. Masland, Tatjana C. Jakobs; Structural Remodeling Of Fibrous Astrocytes After Axonal Injury. Invest. Ophthalmol. Vis. Sci. 2011;52(14):2679.
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Astrocytes respond to virtually all injuries and diseases by becoming reactive. This is characterized by hypertrophy of the soma and processes and an increase in the expression of glial fibrillary acidic protein (GFAP). Because the cells obscure each other in immunostaining, little is known about the morphological changes of a single reactive astrocyte, nor how single astrocytes combine to form the glial scar. Using a transgenic mouse that expresses green fluorescent protein in subsets of astrocytes (hGFAPpr-EGFP), we investigated the behavior of reactive fibrous astrocytes after axonal degeneration in three CNS structures: the glial lamina at the head of the optic nerve, the myelinated portion of the optic nerve, and the corpus callosum.
Astrocytes in the hGFAPpr-EGFP strain express EGFP under the human GFAP promoter (Nolte et al., 2001). This allows for the morphology of an individual astrocyte to be seen in its entirety; even the finest processes are visible. Their morphology and spatial arrangement was examined at 3d, 7d, 2wks and 1mth after an optic nerve crush or cortical stab wound. The optic nerve was crushed for 10 s. Tissue was prepared for either cryo- or vibratome-sectioning and imaged using a laser scanning confocal
Fibrous astrocytes react to injury by undergoing a two-stage remodeling process. They first retract their primary processes, simplifying their shape, and by 3 days post-crush dramatically reducing their spatial coverage by as much as eightfold. In the subsequent week, they partially re-extend long processes, returning to a near normal morphology and an extensive spatial overlap. In the glial lamina, processes do not reorganize to form a honeycomb arrangement. The resulting glial scar consists of an irregular array of astrocyte processes, contrasting with their original orderly arrangement.
These morphological changes are a general feature of fibrous astrocytes in CNS fiber tracts and are in distinct contrast to those reported for protoplasmic astrocytes of the grey matter. The main common feature between the response of fibrous and protoplasmic astrocytes was the hypertrophy of the soma and remaining processes. It is unclear why a two-stage remodeling of fibrous astrocytes is required, and how it contributes to the formation of the glial scar.
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