Research Paper Volume 13, Issue 12 pp 16816—16833
Celastrol protects against early brain injury after subarachnoid hemorrhage in rats through alleviating blood-brain barrier disruption and blocking necroptosis
- 1 Department of Neurosurgery, The Second Affiliated Hospital of Zhejiang University, School of Medicine, Hangzhou 310016, China
- 2 School of Medicine, Zhejiang University, Hangzhou 310012, China
- 3 Neurointensive Care Unit, The Second Affiliated Hospital of Zhejiang University, School of Medicine, Hangzhou 310016, China
- 4 Department of Neurosurgery, Hangzhou First People’s Hospital, Hangzhou 310006, China
- 5 Department of Radiology, The Second Affiliated Hospital of Zhejiang University, School of Medicine, Hangzhou 310016, China
- 6 Department of Radiology, Peking University Shenzhen Hospital, Shenzhen 518034, China
Received: February 8, 2021 Accepted: May 24, 2021 Published: June 28, 2021https://doi.org/10.18632/aging.203221
How to Cite
Copyright: © 2021 Xu et al. This is an open access article distributed under the terms of the Creative Commons Attribution License (CC BY 3.0), which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited.
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.
SAH: Subarachnoid hemorrhage; EBI: early brain injury; OGD: oxygen glucose deprivation; BBB: blood-brain barrier; Cel: Celastrol; MMPs: matrix metalloproteases; IBD: inflammatory bowel disease; HSP: heat shock protein; PI: propidium iodide; AA: adjuvant-induced arthritis; SDS-PAGE: sodium dodecyl sulfate polyacrylamide gel; PVDF: polyvinylidene fluoride.