The Interfering Effects Of Neuregulin On The Cerebral Ischemia Reperfusion In Mice

Objective To study the effects of neuregulin-1β(NRG-1β)on the nervous behavioral function,cerebral infarction volume, brain water content, neurocyte apoptosis and aquaporin-4(AQP-4)expression after cerebral ischemic reperfusion in mice. Methods The models with middle cerebralartery occlusion reperfusion (MCAO/R) were established by intraluminal thread methods in mice.Administering neuregulin-1β(2μg/kg) was injected from internal carotid artery for treatment.Applying Bederson's scores to evaluate the nervous behavioral function, show the cerebral infarctionvolume by tetrazolium chloride (TTC) stain, measuring the brain water content by dry-wet weightcomparing, counting the apotisis positive cells by immunofluorescence and determine the expressionof aquaporin-4 (AQP) by immunohistochemical assay. Results All the mice with left middle cerebralartery occlusion and/or reperfusion showed nervous behavioral malfunction in each group, and thefocus infarction showed up in the ischemic hemisphere. The water content of the brain rose andaquaporin-4 expression was reinforced, and the neurocyte apoptosis proceeded as well. The score ofthe group administered NRG remained significantly smaller on each time spot comared with thecontrol. In the NRG-1βgroup, nervous behavioral malfunction of the 24 hours ischemia group wasobviously slight than the control group; and the infarction volume, the number of apoptosis positivecell of NRG group was smaller, P＜0.05. While the water content of the brain and aquaporin-4expression, compared with the control group, showed no significant difference, P＞0.05. In the 22hours,46hours and 70hours reperfusion groups, those four indices mentioned above had significantdifference with the control groups, P＜0.05. The diversity of water content of the brain had positivecorrelation with the aquaporin-4 expression. Conclusion Neuregulin-1βmight relieve the cerebralischemic reperfusion injury by blocking the related genes'activation of ischemia induced apoptosis,down-regulating the expression of AQP-4 and reducing cerebral edema and infarctionvolume. Therefore, neuregulin may relieve the cerebral ischemia/reperfusion injury and improve theneurological score, so as to protect the brain and its function.