EXPRESSION OF TRANSFORMING GROWTH-FACTOR-BETA-1 AND INTERLEUKIN-1-BETA MESSENGER-RNA IN RAT-BRAIN FOLLOWING TRANSIENT FOREBRAIN ISCHEMIA

Transforming growth factor-beta1 (TGF-beta1) and interleukin-1beta mRNA expression were studied in rat brains after 30 min of global ischemia by in situ hybridization. Ischemia was produced by four-vessel occlusion followed by different recirculation times ranging between 15 min and 7 days. TGF-beta1 mRNA could first be detected 3 days after ischemia in the hippocampus, in layers II/III of cortex, in the striatum and in parts of the ventral thalamus. At 7 days after recirculation a prominent increase in TGF-beta1 mRNA was observed in the CA1 sector of the hippocampus. Induction of interleukin-1beta mRNA, however, was less marked and limited to the rostral striatum 3 and 7 days after ischemia. TGF-beta1 expression 7 days after ischemia correlated well with the histological localization of regions where neuronal degeneration and subsequent astrocytic and microglial activation had occurred. In adjacent brain sections, the distribution of TGF-beta1 mRNA after 7 days closely resembled that of the immunostaining pattern of activated microglia, indicating that at this time point TGF-beta1 mRNA was mainly produced by microglial cells. The late induction of TGF-beta1 mRNA after ischemia points to an involvement in the persistent glial response rather than the initial glial activation. The differential pattern of interleukin-1beta mRNA induction indicates regional variations of cytokine production after ischemic brain lesions.