BS. Department of Neurosurgery - Wuxi Clinical College of Anhui Medical University - 904th Hospital of Joint Logistic Support Force of PLA - Wuxi Clinical College of Anhui Medical University - Wuxi, China.
Acta Cir Bras. 2021 Nov 22;36(10):e361002. doi: 10.1590/ACB361002. eCollection 2021.
Spontaneous intracerebral hemorrhage (ICH) is a major cause of death and disability with a huge economic burden worldwide. Cerebrolysin (CBL) has been previously used as a nootropic drug. Necroptosis is a programmed cell death mechanism that plays a vital role in neuronal cell death after ICH. However, the precise role of necroptosis in CBL neuroprotection following ICH has not been confirmed.
In the present study, we aimed to investigate the neuroprotective effects and potential molecular mechanisms of CBL in ICH-induced early brain injury (EBI) by regulating neural necroptosis in the C57BL/6 mice model. Mortality, neurological score, brain water content, and neuronal death were evaluated by terminal deoxynucleotidyl transferase dUTP nick end labeling (TUNEL) staining, Evans blue extravasation, Western blotting, and quantitative real-time polymerase chain reaction (PCR).
The results show that CBL treatment markedly increased the survival rate, neurological score, and neuron survival, and downregulated the protein expression of RIP1 and RIP3, which indicated that CBL-mediated inhibition of necroptosis, and ameliorated neuronal death after ICH. The neuroprotective capacity of CBL is partly dependent on the Akt/GSK3β signaling pathway.
CBL improves neurological outcomes in mice and reduces neuronal death by protecting against neural necroptosis.
自发性脑出血（ICH）是全世界范围内导致死亡和残疾的主要原因，且带来了巨大的经济负担。脑活素（CBL）曾被用作益智药。坏死性凋亡是一种程序性细胞死亡机制，在 ICH 后神经元细胞死亡中起着至关重要的作用。然而，坏死性凋亡在 CBL 脑出血后神经保护中的确切作用尚未得到证实。
在本研究中，我们旨在通过调节 C57BL/6 小鼠模型中的神经坏死性凋亡，研究 CBL 在 ICH 诱导的早期脑损伤（EBI）中的神经保护作用及其潜在的分子机制。末端脱氧核苷酸转移酶 dUTP 缺口末端标记（TUNEL）染色、伊文思蓝渗出、Western blot 和定量实时聚合酶链反应（PCR）评估死亡率、神经评分、脑水含量和神经元死亡。
结果表明，CBL 治疗显著提高了存活率、神经评分和神经元存活率，并下调了 RIP1 和 RIP3 的蛋白表达，这表明 CBL 介导的坏死性凋亡抑制作用，并改善了 ICH 后的神经元死亡。CBL 的神经保护能力部分依赖于 Akt/GSK3β 信号通路。
CBL 通过防止神经坏死性凋亡改善了小鼠的神经功能预后并减少了神经元死亡。
