EGB761 ameliorates cognitive dysfunction and attenuates microglial activation in a mouse model of ischemic stroke
- VernacularTitle:EGB761改善缺血性脑卒中模型小鼠的认知功能障碍并降低小胶质细胞激活
- Author:
Hua WANG
1
;
Chi ZHANG
;
Xiao-Guang ZHANG
Author Information
- Keywords: EGB761; ischemic stroke; mouse; cogni-tive dysfunction; neuron; microglia; TLR4/NF-κB pathway
- From: Chinese Pharmacological Bulletin 2024;40(10):1872-1878
- CountryChina
- Language:Chinese
- Abstract: Aim To investigate the effect of EGB761 on cognitive impairment in mice following ischemic stroke and its underlying mechanism.Methods Sev-enty-two mice were randomly divided into four groups(n=18 each):sham group,model group,low-dose EGB761 treatment group,and high-dose EGB761 treat-ment group.The middle cerebral artery occlusion/reperfusion(MCAO/R)mouse model was established using the thread occlusion method.The low-and high-dose groups received 50 mg·kg-1 and 150 mg·kg-1 of EGB761 respectively,once daily for 28 days after MCAO/R.Cerebral infarction volume was measured u-sing TTC staining.Neurological function was evaluated using the modified neurological function score(mNSS).The learning and cognitive function of mice was assessed by the water maze test.Neuronal apopto-sis was detected through NeuN and TUNEL co-stai-ning.Iba1 immunofluorescence staining was used to e-valuate microglia activation.The protein expression levels of TLR4,p-IKKα and NF-κB were detected by Western blot.Results Compared with the model group,both low-dose and high-dose EGB761 groups exhibited a significant reduction in cerebral infarction volume(P＜0.01),improvement in neurological func-tion as well as learning and cognitive function(P＜0.01),a significant decrease in apoptotic neurons percentage(P＜0.01),along with activated microglia(P＜0.01).Furthermore,expressions of TLR4,p-IKKα and NF-κB were significantly reduced(P＜0.05).Notably,the high-dose treatment demon-strated more pronounced effects than the low-dose treatment did.Conclusion EGB761 can ameliorate neurological and cognitive dysfunction in MACO/R mice by reducing neuronal apoptosis while inhibiting the TLR4/NF-κB pathway to mitigate excessive activa-tion of microglia.
