Preventing inflammatory reaction with estrogen after cerebral ischemia/reperfusion injury

Yun JIANG; Guanghui CHEN; Guoqing ZHOU; Kui MENG

ABSTRACT

BACKGROUND:

Leukocytic infiltration induced by release of inflammatory cytotkines and up-regulation of adhesion molecules is closely associated with the formation of cerebral infarcted focus. The related factors have been widely studied.

OBJECTIVE:

To explore influence of estrogen on inflammatory reaction in rats after focal ischemia/reperfusion injury.

DESIGN:

Randomized controlled experiment.

SETTING:

Nanjing General Hospital, Nanjing Military Area Command of Chinese PLA.MATERIALSThe experiment was performed at the Department of Neurology, Department of Pathology, Nanjing General Hospital, Nanjing Military Area Command of Chinese PLA. Adult male SD rats were selected to establish cerebral ischemic models, with the body mass of 280-350 g.

METHODS:

The rats were assigned into 3 groups control group,ovariectomized group and estrogen treatment group (estradiol, 200 μg/kg,subcutaneous injection, once a week for 4 weeks). Four weeks later, models with right middle cerebral artery occlusion (MCAO) for 1 hour and 2 hours as well as reperfusion for 0, 1, 3, 6, 22 and 70 hours were established with thread embolism method. Mean number of infiltrative neutrophils in brain tissue was calculated under microscope with 10 high power fields in ischemic hemisphere with hematoxylin and eosin staining. Expression of nuclear factor-κB was determined with immunohistochemical method.MAIN OUTCOME

MEASURES:

Infiltration of neutrophils and expression of nuclear factor-κB in brain parenchyma.

RESULTS:

①Expression of nuclear factor-κB There was expression of nuclear factor-κB in the ovariectomized group at hour 1 after ischemia.Positive cells appeared at hour 2 after ischemia in the control group and estrogen treatment group. The expression was in the peak at ischemia for 2hours and reperfusion for 3 hours in the three groups, and decreased gradually. There was slight expression at reperfusion for 70 hours in the ovariectomized group, while there was no clear factor-κB positive cell at reperfusion for 22 hours in the control group and estrogen treatment group.②Infiltrative neutrophils in cerebral ischemic region in the ovariectomized group significantly increased at ischemia for 2 hours and reperfusion for 22 hours. Compared with the estrogen treatment group, there was significant difference (P=0.045). At ischemia for 2 hours and reperfusion for 70 hours,infiltrative neutrophils in the ovariectomized group were more than those in the control group and estrogen treatment group, but there were significant differences only between ovariectomized group and control group.

CONCLUSION:

Estrogen can inhibit inflammatory reaction after cerebral ischemia/reperfusion injury.