Effects of selective head mild hypothermia on endogenous neuroprotection in brain following global cerebral ischemia/reperfusion injury: experiment with dogs

Abstract

To study the effects of selective head mild hypothermia on endogenous neuroprotection in brain following global cerebral ischemia/reperfusion. Fifteen dogs were randomly divided into three groups: nonischemic control group (Group A, n = 4), undergoing thoracotomy without cerebral ischemia and general care for 8 hours thereafter; cerebral ischemia/reperfusion group (Group B, n = 5) undergoing thoracotomy, clipping of the ascending aorta for 18 min, cardiac resuscitation, maintenance of respiration and circulation for 8 h; and mild hypothermia group (Group C, n = 6), received selective head mild hypothermia, i.e. lowering the tympanic temperature to (34 +/- 0.5) degrees C for 8 hours after cerebral ischemia. The neurological function was assessed by Glasgow coma scale and Pittsburgh brain stem score. At the end of experiment, the dog brains were taken out to obtain the right parietal cerebral cortex. Immunohistochemistry was used to detect the parvalbumin (PV) and HSP(70). Xanthine oxidase method was used to detect the superoxide dismutase (SOD) activities: total SOD (T-SOD), manganese SOD (Mn-SOD), and copper-zinc SOD (Cu-ZnSOD). Spectrophotometry was used to detect the activities of glutathione (GSH) and glutathione peroxidase (GSH-Px). The comprehensive neurological score of Group C was 23.4 +/- 1.5, significantly higher than that of Group B (18.6 +/- 1.0, P < 0.05). The cerebral cortex of Group A showed a lot of PV positive neurons, the density of PV-positive neurons decreased significantly in Group B (P < 0.05), and the density of PV-positive neurons win Group C was significantly higher then that of Group B, however, still significantly lower than that of Group A (both P < 0.05). The density of HSP70-LI neurons of Group A was very low (5.5 +/- 2.1), those of Groups B and C were significantly higher than that of Group A (15.6 +/- 3.7 and 27.1 +/- 4.9 respectively, P < 0.05 or P < 0.01), that of Group C being significantly higher than that of Group B (P < 0.05). The contents of GSH, T-SOD, MnSOD, Cu-ZnSOD, and GSH-Px of Group B were all significantly lower than those of Group A (P < 0.05 or P < 0.01). The contents of GSH, T-SOD, and Cu-ZnSOD of Group C were significantly higher than those of Group B (P < 0.05 or P < 0.01), Mild hypothermia may up-regulate the endogenous neuroprotection in brain tissue following cerebral ischemia/reperfusion and may be beneficial to cerebral ischemia.