Therapeutic effect and mechanism of neuregulin on cerebral ischemia reperfusion injury in mice
- VernacularTitle:神经调节素治疗小鼠脑缺血再灌注损伤的机制
- Author:
Hongting MA
;
Tao WANG
;
Zhen LI
- Publication Type:Journal Article
- Keywords:
Brain ischemia;
Reperfusion injury;
Brain edema;
Apoptosis;
Neuregulins;
Mice;
Aquaporin 4
- From:
Chinese Journal of Pathophysiology
2009;25(3):460-466
- CountryChina
- Language:Chinese
-
Abstract:
AIM: To study the effects of neuregulin-1β (NRG-1β) on the nervous behavioral function, cerebral infarction volume, brain water content (BWC), neuroal apoptosis and aquaporin-4 (AQP-4) expression in astrocytes after cerebral ischemic reperfusion in mice. METHODS: Intraluminal thread methods were applied to establish the middle cerebral artery occlusion reperfusion (MCAO/R) model in mice. Neuregulin-1β (2 μg/kg) was injected into the internal carotid artery for treatment. The nervous behavioral function was evaluated by Bedersons test. The cerebral infarction volume was observed with tetrazolium chloride (TTC) staining. The BWC was measured by calculating the dry-wet weight ratio. The apoptotic positive cells were counted by immunofluorescence assay. The expression of AQP-4 was determined by immunohistochemical method. RESULTS: Nervous behavioral malfunction appeared in all the mice with left middle cerebral artery occlusion (MCAO) and/or reperfusion. The infarction focus showed in the ischemic hemisphere following the injury. The BWC, the numbers of neuroal apoptotic cells and AQP-4 expression in astrocytes were higher than those in sham control group. In MCAO/R+NRG-1β treatment group, the nervous behavioral function at ischemia 24 h significantly improved, the numbers of apoptotic positive cells reduced and the infarction volume decreased significantly than those in MCAO/R group (P<0.05). The BWC and AQP-4 expression in astrocytes showed no significant difference compared with MCAO/R group (P>0.05). In the reperfusion 22 h, 46 h and 70 h groups, the five indexes mentioned above were significantly different from those in the corresponding MCAO/R groups (P<0.05). CONCLUSION: NRG-1β might reduce cerebral edema and infarction volume, and improve the nervous behavioral function via down-regulating the expression of AQP-4 in astrocytes and inhibiting the neuronal apoptosis induced by ischemia reperfusion injury.
