MONITORING THE TEMPORAL AND SPATIAL ACTIVATION PATTERN OF ASTROCYTES IN FOCAL CEREBRAL-ISCHEMIA USING IN-SITU HYBRIDIZATION TO GFAP MESSENGER-RNA - COMPARISON WITH SGP-2 AND HSP70 MESSENGER-RNA AND THE EFFECT OF GLUTAMATE-RECEPTOR ANTAGONISTS

We investigated the temporo-spatial expression of astrocyte glial fibr illary acidic protein (gfap) and sulfated glycoprotein 2 (sgp-2) mRNAs in comparison to 70-kDa heat shock protein (hsp70) mRNA by in situ hy bridisation in rats subjected to permanent occlusion of the middle cer ebral artery (MCA). Gfap mRNA started to increase in the cingulate cor tex of the lesioned hemisphere 6 h after MCA occlusion and gradually s pread over the lateral part of the ipsilateral cortex and the striatum from 12 h to 3 days, peaking at 3 days after MCA occlusion. Gfap mRNA also increased in the contralateral cingulate cortex and corpus callo sum at 12 and 24 h. Hsp70 mRNA increased markedly in the ipsilateral c ortex adjacent to the ischemic lesion, and slightly within the lesion area from 3 to 24 h and disappeared after 3 days. By 7 days, gfap and sgp-2 mRNAs were increased markedly in the peri-infarct area, and in t he ipsilateral thalamus parallel with the delayed neuronal damage, whe reas the widespread increase of gfap mRNA in the ipsilateral hemispher e declined. Post-occlusion treatment with the glutamate receptor antag onists MK-801 and NBQX slightly attenuated the induction of gfap but d id not qualitatively affect the topical expression pattern. Within the cingulate cortex MK-801 treatment resulted in a significant decrease of the signal intensity at all survival times, reflecting most likely an attenuation of lesion-induced spreading depression Like depolarizat ion waves by MK-801. The area of hsp70 expression was reduced by both MK-801 and NBQX, most likely reflecting the decrease of the lesion are a by both treatment regimens. Our study thus revealed an early and wid espread increase of gfap mRNA in the non-ischemic areas including the contralateral hemisphere starting between 3 and 6 h, and a delayed cir cumscribed expression in the peri-infarct border zone after 1 week. Co mparison with the expression of hsp70 mRNA suggests that the absence o f an early gfap mRNA induction in the peri-lesion zone reflects an imp airment of astrocytic function which may be of importance for infarct growth during the early evolution of the pathological process.