CYTOKINES IN CEREBRAL-ISCHEMIA - EXPRESSION OF TRANSFORMING GROWTH-FACTOR-BETA-1 (TGF-BETA-1) MESSENGER-RNA IN THE POSTISCHEMIC ADULT-RAT HIPPOCAMPUS

Transient global cerebral ischemia induces selective neuronal degenera tion in the adult rat hippocampus, which is both preceded and accompan ied by activation of microglia and astrocytes. Altered expression patt erns of cytokines and growth factors might influence the postischemic neuron-glial interactions as well as the degenerative neuronal process es. Northern blotting of hippocampal tissue from ischemic animals reve aled elevated levels of transforming growth factor beta-1 (TGF-beta(1) ) mRNA, and in the present in situ hybridization study we examine the endogenous expression and cellular localization of TGF-beta(1) mRNA in the adult rat hippocampus at various intervals following 10 min of gl obal cerebral ischemia. Six hours after ischemia, a diffuse expression of TGF-beta(1) mRNA was found throughout the brain, which further int ensified until Day 2 and thereafter subsided. In parallel, a massive i ncrease of signal was observed in the hilus fascia dentata from Day 1 and in area CA1 from Day 2 to 4, both areas displaying selective neuro nal degeneration. Peak levels of TGF-beta(1) mRNA were found in the hi lus around Day 4, whereas expression in the CA1 area persisted through Day 21, the latest time point examined. A similar biphasic response, consisting of a transient, generalized reaction and a persistent lesio n-associated activation in areas undergoing selective neuronal degener ation, was previously described for microglia and is reconfirmed in th e present study. Cells of the microglial/macrophage lineage thus inclu de the potent modulatory cytokine TGF-beta(1) in their potential reper toire of responses to both CNS activation and lesioning. (C) 1995 Acad emic Press, Inc.