Empagliflozin Protects Against Ischemic Brain Injury in Mice by Inhibiting Activation of Microglia
10.13748/j.cnki.issn1007-7693.20233120
- VernacularTitle:恩格列净通过抑制小胶质细胞激活改善小鼠缺血性脑损伤
- Author:
Ming CAO
1
;
Xinyu ZHOU
1
;
Suya LIU
1
;
Yun LIU
1
;
Wanqing ZHENG
1
;
Xiangnan ZHANG
1
Author Information
1. College of Pharmaceutical Sciences, Zhejiang University, Hangzhou 310058, China
- Publication Type:Journal Article
- Keywords:
stroke;
empagliflozin;
neurological;
dysfunction
- From:
Chinese Journal of Modern Applied Pharmacy
2024;41(2):146-155
- CountryChina
- Language:Chinese
-
Abstract:
OBJECTIVE:To identify the protective effect of empagliflozin on ischemic brain injury and neurological dysfunction in mice, and further explore its potential mechanism.
METHODS:Acute cerebral ischemia model was induced by the permanent middle cerebral artery occlusion surgery in C57BL/6J mice. Empagliflozin(10 and 30 mg·kg−1) was administered to mice one hour after the onset of occlusion. Brain infarct volume and neurological defect score were assayed 24 h after surgery. Mice were subjected to photo-thrombosis and further administered with empagliflozin 3, 10, 30 mg·kg−1 intragastricly for either 7 or 14 consecutive days. The grid-walking task and the cylinder task were performed daily to determine the sensory-motor function of the mice. Alternatively, the mice were treated with 10 mg·kg−1 empagliflozin simultaneously with 10% glucose(i.p.) for 7 consecutive days after the photo-thrombosis model to evaluate their motor sensory function. Immunofluorescence staining was used to detect the activation of microglia within the infarct area 7 d after the photo-thrombosis.
RESULTS:One hour after permanent middle cerebral artery occlusion surgery, gavage of empagliflozin significantly increased the brain infarct volume and neurological dysfunction. While in photo-thrombosis surgery, treatment of empagliflozin(10 mg·kg−1) for consecutive 7 or 14 days significantly decreased the rate of false foot in grid-walking task and the assymetric index in cylinder task. At the dose of 30 mg·kg−1, however, empagliflozin even aggravated photo-thrombosis-induced neurological dysfunction, while the dose of 3 mg·kg−1 showed no effect. Unexpectedly, the protective effect of empagliflozin(10 mg·kg−1) could not be reversed by glucose treatment. The results of immunofluorescence showed that empagliflozin(10 mg·kg−1) significantly alleviated the microglia activation in the ischemic area after the photo-thrombosis operation.
CONCLUSION:Empagliflozin cannot protect against acute ischemia-induced brain injury in mice. Empagliflozin alleviated ischemia-induced neurological dysfunction with consecutive administration in a dose-related manner. Empagliflozin-conferred neuroprotection may not be attributable to its effects on lowing blood glucose. Alternatively, empagliflozin may play a neuroprotective effect by inhibiting the excessive activation of microglia in ischemic brains.
