Celastrol inhibits glutamate excitotoxicity after subarachnoid hemor-rhage by directly targeting EAAT2
10.3969/j.issn.1000-4718.2024.11.004
- VernacularTitle:雷公藤红素通过直接作用于EAAT2抑制蛛网膜下腔出血后谷氨酸兴奋性毒性损伤
- Author:
Xiaoying LI
1
;
Pida HAO
;
Xiaotong FENG
;
Qile SONG
;
Weiqi WANG
;
Guoqing ZHOU
;
Yajun HOU
Author Information
1. 山东第一医科大学(山东省医学科学院)第二附属医院,山东 泰安 271000
- Keywords:
subarachnoid hemorrhage;
celastrol;
excitatory amino acid transporter 2;
glutamate excitotoxici-ty;
brain edema;
apoptosis
- From:
Chinese Journal of Pathophysiology
2024;40(11):2014-2021
- CountryChina
- Language:Chinese
-
Abstract:
AIM:To investigate the impact of celastrol intervention on excitatory amino acid transporter 2(EAAT2)and its neuroprotective role in subarachnoid hemorrhage(SAH).METHODS:Western blot analysis was uti-lized to assess the EAAT2 expression level within 72 h after SAH,while glutamate concentration in cortical brain tissues was measured.Computational simulation was employed to explore the binding of celastrol with EAAT2.Seventy SD rats were randomly assigned to sham,model,model+GT949(an EAAT2 agonist),model+dihydrokainic acid(DHK;an EAAT2 inhibitor),and model+celastrol groups.Glutamate concentration in cortical brain tissues was quantified,and brain edema was assessed by dry-wet weight method.Western blot analysis was conducted to evaluate the expression of EAAT2,aquaporin 4 and apoptosis-related proteins(Bax,Bcl-2,caspase-3 and caspase-9),and TUNEL staining was employed to assess the apoptotic cell count in each group.RESULTS:(1)EAAT2 level decreased while glutamate con-centration increased.(2)Celastrol was found to directly bind to EAAT2,enhancing EAAT2 expression and reducing glu-tamate concentration after SAH.(3)Celastrol demonstrated the ability to inhibit brain edema after SAH.(4)Celastrol was effective in reducing neuronal apoptosis after SAH.CONCLUSION:Celastrol has the potential to up-regulate EAAT2 expression,lower glutamate level,mitigate brain edema,and decrease neuronal apoptosis after SAH.
