The expression of transforming growth factor-beta1 (TGF-beta 1) in hippocampal neurons: a temporary upregulated protein level after transient forebrain ischemia in the rat

Exogenous TGF-beta 1 has been shown to protect neurons from damage induced in vitro and in vivo. In this study we attempted to examine the expression of endogenous TGF-beta 1 mRNA and protein in the hippocampus of non-ischemi c and ischemic rats, and to localize TGF-beta 1 protein and DNA fragmentati on by double-staining. Transient ischemia was induced for 10 min in Wistar rats by clamping both common carotid arteries and lowering blood pressure t o 40 mmHg. Bioactive TGF-beta 1 was selectively determined in CA1 pyramidal neurons of non-ischemic rats. It was upregulated after 3 h and 6 h of repe rfusion corresponding to the increase in TGF-beta 1 RNA level detected by R T-PCR. Lectin and GFAP staining showed no detectable activated microglial c ells and astrocytes in the hippocampus 3 h and 6 h after ischemia. When neu ronal damage proceeded through day 2 to day 4 after ischemia as demonstrate d by TUNEL-staining, TGF-beta 1 immunoreactivity (ir) disappeared in damage d neurons but persisted in viable neurons although TGF-beta 1 mRNA levels c ontinuously increased. Double-staining revealed that TUNEL-positive neurons did not express TGF-beta 1 while TUNEL-negative neurons in the CA1 subfiel d exhibited a distinct TGF-beta 1 ir. These data indicate that hippocampal CA1 neurons can express TGF-beta 1 under physiological conditions and upreg ulate its expression during the first hours after ischemia, that is indepen dent of the activation of glial cells. The endogenous TGF-beta 1 expressed in neurons may play a role in the pathological process of DNA degradation a nd delayed neuronal death after transient forebrain ischemia. (C) 2000 Else vier Science B.V. All rights reserved.