TIME-COURSE OF CILIARY NEUROTROPHIC FACTOR MESSENGER-RNA EXPRESSION IS COINCIDENT WITH THE PRESENCE OF PROTOPLASMIC ASTROCYTES IN TRAUMATIZED RAT STRIATUM

Adrenal grafting for Parkinson's disease has led to modest functional improvement despite poor graft survival. One explanation is a neurotro phic response within the traumatized striatum. This study was undertak en to investigate the time course of the astrocytic response in vivo a nd in vitro, and the expression of ciliary neurotrophic factor (CNTF) mRNA following striatal injury. Unilateral stereotaxic biopsy of the r at striatum was performed and gelatin sponge (gelfoam) was immediately placed into the biopsy cavity. Rats were sacrificed on days 1, 3, 5, 7, 14, and 28 post biopsy. Immunohistochemical staining of the traumat ized striatum with antibodies to glial fibrillary acidic protein (GFAP ) was carried out, The reactive astrocytes which appeared within 7 day s after trauma were mostly protoplasmic on the basis of morphology, an d maximal on day 7, being 30 times the level in the normal striatum. A fter day 7, fibrous astrocytes appeared and increased up to day 28, wh ile protoplasmic astrocytes decreased. In addition, immunocytochemical double staining of short term cultured astrocytes from the traumatize d striatum with anti-A2B5 and anti-GFAP antibodies revealed that 84% a nd 90% of astrocytes were type 1 astrocytes on days 3 and 7, respectiv ely; however, by day 28 47% of astrocytes were type 2. Northern blot a nalysis revealed that CNTF mRNA expression was up-regulated and peaked on day 7, coincident with a predominance of protoplasmic astrocytes i n vivo and type 1 astrocytes in vitro, respectively. These findings su ggest that the expression of CNTF mRNA is part of the early astrocytic response to trauma, particularly associated with protoplasmic astrocy tes in vivo and type 1 astrocytes in vitro. We conclude that reactive astrocytes are likely candidates to produce the neurite promoting acti vity seen in previous studies after trauma in the striatum. CNTF may r epresent an early signal in the astrocyte-mediated neurotrophic and ne urite promoting responses. (C) 1995 Wiley-Liss, Inc.