REACTIVE ASTROCYTES IN NEONATE BRAIN UP-REGULATE INTERMEDIATE FILAMENT GENE-EXPRESSION IN RESPONSE TO AXONAL INJURY

We have examined the injury response of astrocytes in the immature hamster brain in this study, focusing on alterations in the expression of glial fibrillary acidic protein (GFAP) and vimentin. In the adult CNS these two type Ill intermediate filament (IF) proteins have been shown to undergo robust increases in expression in response to axonal injury. Since injury to the immature CNS reportedly elicits less glial scar formation than adult brain injury, we examined the possibility that immature astrocytes respond differently than adult astrocytes to CNS injury with respect to IF gene expression. In situ hybridization using a 35S-labeled cDNA GFAP probe was done on brainstem sections obtained 2, 7 and 14 days after unilateral transection of the corticospinal tract in P8 hamster pups. The results indicated that substantial increases in GFAP mRNA were associated with the degenerating portion of the corticospinal tract by 2 days after axotomy and that the levels remained elevated for at least 14 days. Double-label immunofluorescence studies of this material suggested that GFAP as well as vimentin protein levels were also increased in many astrocytes in and around the degenerating corticospinal tract 2-14 days after axotomy. Most of the reactive astrocytes in the degenerating regions exhibited increases in GFAP and vimentin immunostaining but some vimentin-negative GFAP-positive reactive astrocytes were also observed, particularly in regions surrounding the actual degenerative zones. The results from these experiments revealed that immature astrocytes have the potential for altering their normal developmental program of GFAP and vimentin expression after injury and mount a response that is qualitatively similar to that of astrocytes after CNS injury in the adult animal.