Objective: To explore the effects of mild hypothermia combined with ifenprodil on the survival of neuronal and translocation of apoptosis inducing factor (AIF) following global cerebral ischemia-reperfusion to understand the mechanism of combination in cerebral resuscitation.
Methods: Eighty male SD rats were randomly divided into 5 groups of sham (I), model (II), ifenprodil (III), mild hypothermia (IV) and ifenprodil plus mild hypothermia (V) (n = 16 each). Group I completed all procedures except for ventricular fibrillation (VF) and cardio pulmonary resuscitation (CPR). For groups II and V, the model of global cerebral ischemia-reperfusion was established and VF induced with transoesophageal cardiac pacing; groups III and V received by an intraperitoneal injection of ifenprodil immediately after reperfusion and other groups had an equal volume of distilled water. Rectal temperature was cooled down to (32 ± 1)°C in groups IV and V by rubbing body surface with ethanol in 10 min after reperfusion and maintained 4 hours continuously while other groups at (37 ± 1)°C. In hippocampal CA1 region at 24 hours after reperfusion, the pathomorphological changes and quantity of pyramidal cells were detected with hematoxylin and eosin staining, nuclear translocation of AIF was shown with immunofluorescence technique and the nuclear expression level of AIF was measured with Western blot.
Results: Compared with group I (75.0 ± 3.2), the number of pyramidal cells decreased in other groups (P < 0.05); compared with group II (36.0 ± 1.2), the number increased in group III (46.8 ± 1.3), IV (49.0 ± 2.7) and V (61.3 ± 2.60) (P < 0.05). In particular, cell count increased significantly in group V (P < 0.05). Compared to group I, the translocation of AIF form mitochondria to nucleus was detected in other groups; compared with group I (0.022 ± 0.003), the expression level of AIF in the nucleus was higher in other groups (P < 0.05). Compared with group II (1.020 ± 0.029) , the expression levels of AIF in groups III (0.870 ± 0.016), IV (0.820 ± 0.050) and V (0.550 ± 0.050) were lower (P < 0.05). And it decreased significantly in group V (P < 0.05).
Conclusion: Mild hypothermia plus ifenprodil may alleviate neuronal damage after global cerebral ischemia/reperfusion injury through mitigating its pro-apoptotic role after AIF translocation.