Department of Neurosurgery, The Second Affiliated Hospital of Zhejiang University, School of Medicine, Hangzhou 310016, China.
School of Medicine, Zhejiang University, Hangzhou 310012, China.
Aging (Albany NY). 2021 Jun 28;13(12):16816-16833. doi: 10.18632/aging.203221.
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.
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.
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.
Celastrol exhibits neuroprotective effects on EBI after SAH and deserves to be further investigated as an add-on pharmaceutical therapy.
蛛网膜下腔出血（SAH）是一种在全球范围内危及生命的疾病，目前仍缺乏有效的药物治疗方法。白藜芦醇是一种植物来源的三萜类化合物，在多种类型的脑损伤中显示出神经保护作用。本研究旨在探讨白藜芦醇对蛛网膜下腔出血后早期脑损伤（EBI）的影响。
本研究共使用了 61 只雄性 Sprague-Dawley 大鼠。采用血管内穿剌法建立大鼠蛛网膜下腔出血模型，模拟蛛网膜下腔出血后 EBI 的病理变化。通过 3.0T MRI 扫描、免疫组织化学、Western blot 和碘化丙啶（PI）标记等多种方法，探讨白藜芦醇对蛛网膜下腔出血的治疗作用。
白藜芦醇治疗可减轻蛛网膜下腔出血引起的脑水肿，减少 MRI 扫描中的 T2 病变体积和脑室体积，并改善整体神经功能评分。白蛋白渗漏和紧密连接蛋白的降解在白藜芦醇给药后也得到改善。白藜芦醇通过抑制 MMP-9 表达和抗神经炎症作用来保护血脑屏障的完整性。此外，坏死性凋亡相关蛋白 RIP3 和 MLKL 的表达下调，白藜芦醇治疗的蛛网膜下腔出血组基底皮质中的 PI 阳性细胞较未治疗的蛛网膜下腔出血组减少。
白藜芦醇对蛛网膜下腔出血后 EBI 具有神经保护作用，值得作为附加药物治疗进一步研究。
