TRANSFORMING GROWTH-FACTOR-BETA-1 PREVENTS GLUTAMATE NEUROTOXICITY INRAT NEOCORTICAL CULTURES AND PROTECTS MOUSE NEOCORTEX FROM ISCHEMIC-INJURY INVIVO

Transforming growth factor-beta1 (TGF-beta1) has been shown to be an i njury-related peptide growth factor within the mammalian central nervo us system. We tested whether TGF-beta1 has the capacity to protect rat neocortical neurons against excitotoxic damage in vitro and mouse neo cortex against ischemic injury in vivo. After 14 days in vitro, cultur ed neurons from rat cerebral cortex were exposed to 1 mM L-glutamate i n serum-free culture medium. The cultures received TGF-beta1 immediate ly after the addition of glutamate. Eighteen hours later, the cell via bility of the cultures was determined using trypan blue exclusion. TGF -beta1 (1-10 ng/ml) significantly reduced the excitotoxic neuronal dam age in a concentration-dependent manner. In vivo, male NMRI mice were subjected to a permanent occlusion of the left middle cerebral artery by microbipolar electrocoagulation. After 48 h, the animals received a transcardiac injection of carbon black. The area of ischemia (devoid of carbon) was restricted to the neocortex and its size was determined planimetrically by means of an image-analyzing system. The treatment with TGF-beta1 (1 mug/kg i.c.v.) at 6, 4, or 2 h prior to vessel occlu sion reduced the area of ischemia by 5.3, 10.0, and 9.6%, respectively . The effect of the treatment with TGF-beta1 was statistically signifi cant (p < 0.05 by two-way ANOVA). The present in vitro and in vivo dat a suggest that TGF-beta1 has the capacity to diminish the deleterious consequences of an excitotoxic or ischemic insult.