Effects of local mild hypothermia on the expression of EMAP-II and proEMAP-II after cerebral ischemia and reperfusion

Abstract

Objective To investigate the effects of local mild hypothermia on the expression of EMAP-Ⅱ and proEMAP-Ⅱ after cerebral ischemia and reperfusion in rats and to explore the possible neuroprotection mechanism of mild hypothermia.Methods Forty-four male Wistar rats were divided randomly into a sham-operation group (Sham),a normothermia group (NT) and a hypothermia group (HT).Middle cerebral artery occlusion was performed using Longa's method,and reperfusion was allowed after 2 hours of occlusion.Mild hypothermia (33.0 ± 0.5)℃ for 6 hours was initiated at the start of reperfusion,followed by rewarming.Brains were harvested after 6,12,24,48 and 72 hours of reperfusion and used for HE staining to evaluate cellular apzoptosis and immunohistochemical staining for detecting the expression EMAP-Ⅱ and proEMAP-Ⅱ.Results The expression of EMAP-Ⅱ and proEMAP-Ⅱ in the ischemic penumbra was significant at 6 hours in the normothermia and hypothermia groups.It peaked at 12 hours in the normothermia group and 24 hours in the hypothermia group,and then decreased gradually.At 72 hours the expression of EMAP-Ⅱ and proEMAP-Ⅱ in the ischemic penumbras was very close to that in the sham group.EMAP-Ⅱ-positive cells were significantly fewer in the hypothermia group than in the normothermia group at all time points.ProEMAP-Ⅱ-positive cells were significantly more numerous in the normothermia group than in the hypothermia group at 6,12 and 24 hours.Conclusions Mild hypothermia (33.0 ± 0.5) ℃ has a valid neuroprotective effect which involves reducing EMAP-Ⅱ and proEMAP-Ⅱ expression in the ischemic penumbra and inhibiting apoptosis and inflammatory reactions after cerebral ischemia and reperfusion,at least in rats. Key words: Cerebral ischemia; Cerebral reperfusion; Hypothermia; EMAP-Ⅱ ; Apoptosis