Transforming growth factor- s (TGF 1-3) are involved in the regulation of proliferation, differentiation, and survival of various cell types. Previously, we described TGFexpression in the intact rat brain. In the present study, induction of TGF- s was examined after focal ischemia elicited by middle cerebral artery occlusion (MCAO) in the rat. The middle cerebral artery was occluded for 1h except for a group of animals with permanent 24h occlusion. The expression patterns of TGF- s were examined by in situ hybridization histochemistry at 3h, 24h, 72h and 1 month after MCAO. The mRNA levels of TGF- s were only slightly elevated 3h after MCAO. In contrast, 24h later, TGF- 1 showed elevated expression level in the penumbra around the lesion and in the II and V ipsilateral cortical layers. By 72h after the occlusion, TGF- 1 mRNA-expressing cells also appeared within the infarct area and in the corpus callosum. The tissue was largely dissolved within the infarct area 1 month after the ischemic attack. Nevertheless, TGF- 1 mRNA-expression remained high around the lesion. The expression patterns of TGF- 2 and 3 were markedly different: mRNAs of these subtypes were increased in layers II, III, and V of the ipsilateral cerebral cortex without any induction in the caudate putamen 24h after MCAO. The induction was even more pronounced after 24h permanent occlusion with similar expression patterns. However, TGF- 2 and 3 mRNA levels were reduced outside the infarct area by 72h after the occlusion without any appearance of TGF- 2 and 3 mRNA within the lesioned area. By 1 month after the occlusion TGF- 2 and 3 mRNAs are present in small cell groups near to the lesionned area. The observations suggest that endogenous TGF- 1 and TGF- 2 and 3 may participate in neuroprotection although they are induced by different mechanisms following an ischemic attack.

Support: 

Bolyai Fellowship, OTKA NNF85612 and K100319 grants for AD.