Celastrol Protects Against Early Brain Injury After Subarachnoid Hemorrhage in Rats Through Alleviating Blood-brain Barrier Disruption and Blocking Necroptosis

Overview

Journal Aging (Albany NY)

Specialty Geriatrics

Date 2021 Jun 28

PMID 34182541

Citations 9

Authors

Hangzhe Xu

Yong Cai

Mengyan Yu

Jing Sun

Jing Cai

Jingbo Li

Bing Qin

Guangyu Ying

Ting Chen

Yongfeng Shen

Liyong Jie

Demin Xu

Chi Gu

Chun Wang

Xiaoyi Hu

Jingsen Chen

Lin Wang

Gao Chen

Affiliations

Soon will be listed here.

Abstract

Background: Subarachnoid hemorrhage (SAH) is a life-threatening disease worldwide, and effective pharmaceutical treatment is still lacking. Celastrol is a plant-derived triterpene which showed neuroprotective potential in several types of brain insults. This study aimed to investigate the effects of celastrol on early brain injury (EBI) after SAH.

Methods: A total of sixty-one male Sprague-Dawley rats were used in this study. Rat SAH endovascular perforation model was established to mimic the pathological changes of EBI after SAH. Multiple methods such as 3.0T MRI scanning, immunohistochemistry, western blotting and propidium iodide (PI) labeling were used to explore the therapeutic effects of celastrol on SAH.

Results: Celastrol treatment attenuated SAH-caused brain swelling, reduced T2 lesion volume and ventricular volume in MRI scanning, and improved overall neurological score. Albumin leakage and the degradation of tight junction proteins were also ameliorated after celastrol administration. Celastrol protected blood-brain bairrer integrity through inhibiting MMP-9 expression and anti-neuroinflammatory effects. Additionally, necroptosis-related proteins RIP3 and MLKL were down-regulated and PI-positive cells in the basal cortex were less in the celastrol-treated SAH group than that in untreated SAH group.

Conclusions: Celastrol exhibits neuroprotective effects on EBI after SAH and deserves to be further investigated as an add-on pharmaceutical therapy.

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