Kho A Ra, Hong Dae Ki, Kang Beom Seok, Park Woo-Jung, Choi Kyung Chan, Park Kyoung-Ha, Suh Sang Won
Department of Physiology, College of Medicine, Hallym University, Chuncheon 24252, Korea.
Division of Cardiovascular Disease, Hallym University Medical Center, Anyang 14068, Korea.
Int J Mol Sci. 2021 Apr 22;22(9):4385. doi: 10.3390/ijms22094385.
(1) Background and Purpose: Global cerebral ischemia-induced severe hypoxic brain damage is one of the main causes of mortality and long-term neurologic disability even after receiving early blood reperfusion. This study aimed to test the hypothesis that atorvastatin potentially has neuroprotective effects in global cerebral ischemia (GCI). (2) Methods: We performed two sets of experiments, analyzing acute (1-week) and chronic (4-week) treatments. For the vehicle (Veh) and statin treatments, 1 mL of 0.9% saline and 5 mg/kg of atorvastatin (ATOR) were administered orally. For histological analysis, we used the following staining protocols: Fluoro-Jade B and NeuN, 4-hydroxynonenal, CD11b and GFAP, IgG, SMI71, and vWF. Finally, we evaluated the cognitive function with a battery of behavioral tests. (3) Results: The GCI-ATOR group showed significantly reduced neuronal death, oxidative stress, inflammation, and BBB disruption compared with the GCI-Veh group. Moreover, the GCI-ATOR group showed decreased endothelial damage and VV proliferation and had significantly improved cognitive function compared with the GCI-Veh group in both models. (4) Conclusions: ATOR has neuroprotective effects and helps recover the cognitive function after GCI in rats. Therefore, administration of atorvastatin may be a therapeutic option in managing GCI after CA.
(1) 背景与目的:即使在接受早期血液再灌注后,全脑缺血诱导的严重缺氧性脑损伤仍是导致死亡和长期神经功能残疾的主要原因之一。本研究旨在验证阿托伐他汀对全脑缺血(GCI)可能具有神经保护作用这一假说。(2) 方法:我们进行了两组实验,分析急性(1周)和慢性(4周)治疗情况。对于载体(Veh)和他汀类药物治疗,口服给予1 mL 0.9%生理盐水和5 mg/kg阿托伐他汀(ATOR)。对于组织学分析,我们使用了以下染色方案:荧光玉髓B和NeuN、4-羟基壬烯醛、CD11b和GFAP、IgG、SMI71和vWF。最后,我们通过一系列行为测试评估认知功能。(3) 结果:与GCI-Veh组相比,GCI-ATOR组的神经元死亡、氧化应激、炎症和血脑屏障破坏显著减少。此外,在两个模型中,与GCI-Veh组相比,GCI-ATOR组的内皮损伤和血管新生减少,认知功能显著改善。(4) 结论:ATOR具有神经保护作用,有助于大鼠GCI后认知功能的恢复。因此,给予阿托伐他汀可能是心脏骤停后管理GCI的一种治疗选择。