Neuro-protective 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 caroteral artery ligation and given 8% oxygen for 2h) were randomly allocated to HI-37℃group(A),HI-37℃+zVAD(B),HI-29℃(C),HI-29℃+zVAD-fmk(D) and placebo group(E). The control group(F) was sham-operated 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 at 24h after HI insult. The effects on body weights gain (percentage of increased weight, WIP), macroscopical changes (percentage of cortox and hippocampal dead neurons) and expression level of Caspase-3 in the cortex and hippocampus were assessed at 14d. Y-maze was used to explore the behaviors of discrimination learning and memory in 30d HIBD rats.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 group A. The most obvious attenuation was observed in group D. No significant difference existed between group E and group F. Compared with the control group, the differences of the percentage of increased weight at 14d in hypothermia and/or zVAD-fmk treated groups were not statistically significant. Microscopic examination showed that cortox and hippocampus neural death rate in the zVAD-fmk-treated group was proved significantly reduced compared with that in the HI group. Compared with that in HI group, the discriminative learning times in hypothermia and/or zVAD-fmk treated groups decreased,and the memory retention rate increased,the differences of which were significant.Conclusion Mild hypothermia and/or zVAD-fmk showed protective effects on brain HI damage in neonatal rats. The optimal effect was obtained when Mild hypothermia and zVAD-fmk were simultaneously used.