North Sichuan Medical College, Nanchong, Sichuan, China; Department of Neurology, Xichang People's Hospital, Xichang, Sichuan, China.
North Sichuan Medical College, Nanchong, Sichuan, China.
J Stroke Cerebrovasc Dis. 2024 Jul;33(7):107738. doi: 10.1016/j.jstrokecerebrovasdis.2024.107738. Epub 2024 May 1.
Edaravone dexborneol is neuroprotective against ischemic stroke, with free radical-scavenging and anti-inflammatory effects, but its effects in hemorrhagic stroke remain unclear. We evaluated whether edaravone dexborneol has a neuroprotective effect in intracerebral hemorrhage, and its underlying mechanisms.
Bioinformatics were used to predict the pathway of action of edaravone dexborneol. An intracerebral hemorrhage model was established using type IV collagenase in edaravone dexborneol, intracerebral hemorrhage, Sham, adeno-associated virus + edaravone dexborneol, and adeno-associated virus + intracerebral hemorrhage groups. The modified Neurological Severity Score was used to evaluate neurological function in rats. Brain water content was measured using the dry-wet weight method. Tumor necrosis factor-α, interleukin-1β, inducible nitric oxide synthase, and γ-aminobutyric acid levels were determined by enzyme-linked immunosorbent assay. The expression levels of neurofilament light chain and γ-aminobutyric acid transaminase were determined by western blot. Nissl staining was used to examine neuronal morphology. Cognitive behavior was evaluated using a small-animal treadmill.
Edaravone dexborneol alleviated neurological defects, improved cognitive function, and reduced cerebral edema, neuronal degeneration, and necrosis in rats with cerebral hemorrhage. The expression levels of neurofilament light chain, tumor necrosis factor-α, interleukin-1β, inducible nitric oxide synthase, and γ-aminobutyric acid were decreased, while γ-aminobutyric acid transaminase expression was up-regulated.
Edaravone dexborneol regulates γ-aminobutyric acid content by acting on the γ-aminobutyric acid transaminase signaling pathway, thus alleviating oxidative stress, neuroinflammation, neuronal degeneration, and death caused by excitatory toxic injury of neurons after intracerebral hemorrhage.
依达拉奉右莰醇具有清除自由基和抗炎作用，对缺血性脑卒中具有神经保护作用，但对出血性脑卒中的作用尚不清楚。本研究评估了依达拉奉右莰醇对脑出血是否具有神经保护作用及其潜在机制。
采用生物信息学方法预测依达拉奉右莰醇的作用途径。使用 IV 型胶原酶建立脑出血模型，将大鼠分为依达拉奉右莰醇脑出血组、假手术组、腺相关病毒+依达拉奉右莰醇组、腺相关病毒+脑出血组。采用改良神经功能缺损评分评估大鼠的神经功能，干湿重法测量脑水含量，酶联免疫吸附法检测肿瘤坏死因子-α、白细胞介素-1β、诱导型一氧化氮合酶和γ-氨基丁酸的水平，Western blot 检测神经丝轻链和γ-氨基丁酸转氨酶的表达水平，尼氏染色观察神经元形态，小动物跑步机评估认知行为。
依达拉奉右莰醇可减轻脑出血大鼠的神经缺陷，改善认知功能，降低脑水肿、神经元变性和坏死。同时，下调神经丝轻链、肿瘤坏死因子-α、白细胞介素-1β、诱导型一氧化氮合酶和γ-氨基丁酸的表达水平，上调γ-氨基丁酸转氨酶的表达水平。
依达拉奉右莰醇通过作用于γ-氨基丁酸转氨酶信号通路调节γ-氨基丁酸含量，减轻脑出血后神经元兴奋毒性损伤引起的氧化应激、神经炎症、神经元变性和死亡。
