Neuroprotective effects of hypothermia and Caspase inhibitor on hypoxic-ischemic brain damage in neonatal rats

Objective To investigate the protective effects of mild hypothermia and/or Caspase inhibitor(zVAD-fmk:benzyloxycarbonyl-Val-Ala-Asp-fluoromethyl ketone) on hypoxic-ischemic brain damage(HIBD).Methods The model rats(subjected to unilateral left carotereal artery ligation and given 8% oxygen for 2h) were randomly allocated to HI-29℃ group(A),zVAD(B),HI-29℃+zVAD(C),HI-37℃ (D) and placebo group(E).The control group(F)was shamoperated animals.Changes of brain edema,expression of Caspase-3 in the cortex and hippocampus,percentage of hippocampal dead neurons(HDNP) and apoptotic cells in the hippocampus were investigated.Results Brain edema, expression of Caspase-3 in the cortex and hippocampus,HDNP and apoptotic cells in the hippocampus were significantly decreased in group B,C and D compared with those in group A.The most obvious attenuation was observed in group D.No significant difference existed between group E and group F.Conclusion Mild hypothermia and/or zVAD-fmk have protective effects on HIBD,especially when mild hypothermia and zVAD-fmk are used simultaneously.