1.Empagliflozin Protects Against Ischemic Brain Injury in Mice by Inhibiting Activation of Microglia
Ming CAO ; Xinyu ZHOU ; Suya LIU ; Yun LIU ; Wanqing ZHENG ; Xiangnan ZHANG
Chinese Journal of Modern Applied Pharmacy 2024;41(2):146-155
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.
2.Influence of gut microbiota-derived trimethylamine N-oxide on early neurological deterioration in diabetic patients with acute ischemic stroke
Jiaojie HUI ; Feng WANG ; Xuqiang MAO ; Jianping ZHANG ; Suya LI ; Tingting CAO ; Yachen SHI ; Guangjun XI
Chinese Journal of Geriatrics 2023;42(7):794-798
Objective:To investigate the influence of trimethylamine N-oxide(TMAO)on the development of early neurological deterioration(END)in diabetic patients with acute ischemic stroke.Methods:In this cross-sectional study, 108 type 2 diabetes patients with acute ischemic stroke treated at the Department of Neurology in the Affiliated Wuxi People’s Hospital of Nanjing Medical University between October 2019 and November 2020 were consecutively recruited.END was defined as an increase in the National Institutes of Health Stroke Scale(NIHSS)≥ 2 points and exclusion of intracranial hemorrhage or bleeding transformation in cranial imaging evaluation within 5 days of initial deterioration of neurological dysfunction.The patients were divided into 2 groups, an END(n=36)group and a non-END group(n=72). Fasting plasma TMAO was measured using isotope dilution liquid chromatography coupled to tandem mass spectrometry.Results:Of the 108 patients, 36(33.3%)were diagnosed with END, and their plasma TMAO levels were significantly higher compared with patients without END( Z=-3.500, P<0.001). For prediction of END, the area under the ROC curve for plasma TMAO levels was 0.707(95% CI: 0.603-0.811, P<0.001). The frequencies of END in subjects grouped via tertiles of TMAO were 22.2%, 19.4% and 58.3%, respectively, with significant differences between the 3 groups( χ2=14.979, P=0.001). Univariate analysis showed that elevated TMAO( OR=1.160, 95% CI: 1.050-1.282, P=0.004)was associated with END.A multivariate logistic regression model further confirmed the association between TMAO and END( OR=1.145, 95% CI: 1.033-1.269, P=0.010). Conclusions:Increased plasma TMAO levels are associated with END in diabetic patients with acute ischemic stroke.
3.A case report of biotin-thiamine-responsive basal ganglia disease
Guangjun XI ; Jianping ZHANG ; Feng WANG ; Lu YU ; Tingting CAO ; Suya LI
Chinese Journal of Neurology 2022;55(8):868-872
Biotin-thiamine-responsive basal ganglia disease is a rare treatable autosomal recessive neurometabolic disorder caused by mutations in SLC19A3 gene, encoding a transporter of thiamine across the plasma membrane. In the present study, a 29-year-old male patient with epilepsy as the first symptom, accompanied by hypokinesia, extraocular muscle paralysis and delayed dystonia was reported. The brain magnetic resonance imaging revealed abnormal symmetrical signals of bilateral caudate nucleus and lenticular nucleus. The patient was diagnosed as biotin-thiamine-responsive basal ganglia disease by gene detection. After treatment with biotin and thiamine, the symptoms were relieved and the brain lesions subsided.
4.Effects of hyperbaric oxygen combined with the intervention of functional position keeping pillow for the hemiplegic hand on the efficacy and motor function of hemiplegic patients after brain injury
Suya CAO ; Chunyan GE ; Yiqiu CUI ; Yixiang GUAN
Chinese journal of nautical medicine and hyperbaric medicine 2021;28(6):728-731
Objective:To study the effects of hyperbaric oxygen (HBO) combined with the intervention of functional position keeping pillow for the hemiplegic hand on the efficacy and motor function of hemiplegic patients after brain injury.Methods:A total of 90 patients with hemiplegia after brain injury treated in Hai’an People’s Hospital from January 2017 to January 2020 were selected as the research subjects and divided into observation group and control group according to the random number table method, with 45 cases in each group. Both groups were given the intervention of functional position keeping pillow for the hemiplegic hand. The observation group was additionally treated with HBO. All patients received two-month treatment. The hand function was evaluated by the Brunnstrom Hand Function Scale and Barthel Index. The severity of pain was evaluated by the visual analogue scale (VAS). The conditions of hand care were evaluated by the hand care scale (including pressure sores, cleanliness, moisture, odor) designed by Hai’an People’s Hospital. The rehabilitation compliance was evaluated by the Posttraumatic Growth Inventory (PTGI) score and the Chinese version of the Connor-Davidson Resilience Scale (CD-RISC).Results:After treatment, the scores of Brunnstrom Hand Function Scale and Barthel Index of the two groups were significantly increased, and the scores of the observation group were significantly higher than those of the control group ( P<0.05); the VAS scores of the two groups were significantly decreased, and the scores of the observation group were significantly lower than those of the control group ( P<0.05); in terms of pressure sores, cleanliness, moisture, odor, and swelling degree, the scores of the observation group were significantly lower than those in the control group ( P<0.05); the scores of PTGI and CD-RISC of the two groups were significantly increased, and the scores of the observation group were significantly higher than those of the control group ( P<0.05). Conclusion:After brain injury, hyperbaric oxygen combined with the intervention of functional position keeping pillow for the hemiplegic hand can significantly improve the motor function of patients.
5.Effects of hyperbaric oxygen combined with the intervention of functional position keeping pillow for the hemiplegic hand on the efficacy and motor function of hemiplegic patients after brain injury
Suya CAO ; Chunyan GE ; Yiqiu CUI ; Yixiang GUAN
Chinese journal of nautical medicine and hyperbaric medicine 2021;28(6):728-731
Objective:To study the effects of hyperbaric oxygen (HBO) combined with the intervention of functional position keeping pillow for the hemiplegic hand on the efficacy and motor function of hemiplegic patients after brain injury.Methods:A total of 90 patients with hemiplegia after brain injury treated in Hai’an People’s Hospital from January 2017 to January 2020 were selected as the research subjects and divided into observation group and control group according to the random number table method, with 45 cases in each group. Both groups were given the intervention of functional position keeping pillow for the hemiplegic hand. The observation group was additionally treated with HBO. All patients received two-month treatment. The hand function was evaluated by the Brunnstrom Hand Function Scale and Barthel Index. The severity of pain was evaluated by the visual analogue scale (VAS). The conditions of hand care were evaluated by the hand care scale (including pressure sores, cleanliness, moisture, odor) designed by Hai’an People’s Hospital. The rehabilitation compliance was evaluated by the Posttraumatic Growth Inventory (PTGI) score and the Chinese version of the Connor-Davidson Resilience Scale (CD-RISC).Results:After treatment, the scores of Brunnstrom Hand Function Scale and Barthel Index of the two groups were significantly increased, and the scores of the observation group were significantly higher than those of the control group ( P<0.05); the VAS scores of the two groups were significantly decreased, and the scores of the observation group were significantly lower than those of the control group ( P<0.05); in terms of pressure sores, cleanliness, moisture, odor, and swelling degree, the scores of the observation group were significantly lower than those in the control group ( P<0.05); the scores of PTGI and CD-RISC of the two groups were significantly increased, and the scores of the observation group were significantly higher than those of the control group ( P<0.05). Conclusion:After brain injury, hyperbaric oxygen combined with the intervention of functional position keeping pillow for the hemiplegic hand can significantly improve the motor function of patients.


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