Transforming growth factor-bs (TGF-b1-3) form a small group of related cytokines involved in the regulation of proliferation, differentiation, and survival of various cell types. TGF-b was suggested to be neuroprotective because injection of TGF-b decrease while injection of antagonists of TGF-b action increase the infarct size.

Previously, we described the expression patterns of different TGF-b subtypes in the intact rat brain and the time course of their induction following MCAO. The present study identified the cell types of TGF-b1 and -b2 expression in the brain after different survival periods following MCAO using a combination of in situ hybridization histochemistry for TGF-bs and immunolabeling for neural, astroglial and microglial markers. At 24h after focal ischemia, around the lesion most TGF-b1-expressing cells co-localized with IBA-1, a microglial marker, while a few TGF-b1-expressing cells co-localized with GFAP, an astroglial marker. By 72h after the occlusion, TGF-b1 mRNA-expressing cells also appeared in microglia within the ischemic core. TGF-b2 was expressed only in NeuN-positive cells in the II. and V cortical layers at 24h after the occlusion. None of the TGF-b2-expressing cells contained GFAP or IBA-1 immunoreactivity. By 72h after focal ischemia TGF-b2 expression did not change. At 1 month after occlusion, the ischemic tissue was largely dissolved and demarcated by a glial scar. TGF-b1 co-localized around the lesion with microglial markers. TGF-b2 was also expressed in some microglial cells distributed in small cell groups near the lesion. These results suggest that TGF-b1 and TGF-b2 and -b3 have different ways of induction and possibly participate in separate neuroprotective mechanisms that involve distinct cell types.

Support: Bolyai Fellowship, OTKA NNF85612 and K100319 grants for AD.