Hypothermic intervention for 3 hours inhibits apoptosis in neonatal rats with hypoxic-ischemic brain damage

A neonatal rat model of hypoxic-ischemic brain damage was designed and implemented in this study. Rats were subjected to hypothermia at 31 degrees C immediately following hypoxia-ischemia for either 3, 6 or 15 hours. TdT-mediated dUTP nick end labeling demonstrated that the number of apoptotic cells was reduced in the rat cerebral cortex, hippocampus and periventricular white matter following hypothermia. Immunohistochemistry revealed that Bcl-2 and p16 expression were decreased. Inhibition of apoptosis was greatest with the 3 hour hypothermic treatment, followed by hypothermia for 6 hours. In contrast, hypothermia for 15 hours led to a decrease in neuronal number in the cerebral cortex. The results demonstrate that hypothermic intervention at 31 degrees C protects brain tissue against hypoxic-ischemic brain damage by inhibiting apoptosis, and that the optimal length of treatment is 3 hours.