Chen Wei, Guo Yijun, Yang Wenjin, Zheng Ping, Zeng Jinsong, Tong Wusong
Restor Neurol Neurosci. 2017;35(2):217-224. doi: 10.3233/RNN-160705.
Oxidative stress is an important factor in the pathophysiologic changes after traumatic brain injury (TBI). Connexin43 (Cx43) was reported to contribute to cerebral damage. However, the impacts of Cx40 have not been investigated in detail.
In the present study, we hypothesized that Cx40 was involved in oxidative stress-induced brain injury after TBI.
The controlled cortical impact (CCI) model was introduced to Wistar rats as a TBI model. Neurological deficits, oxidative stress and Cx40 were evaluated in TBI rats and N-acetylcysteine (NAC)-treated TBI rats. Neurological severity score (NSS) was used to assess neurological deficits. Brain infarction was measured by histo-staining. Brain edema was evaluated by measuring the brain water content. Cortex samples were collected to measure the tissue levels of malonyldialdehyde (MDA), nitric oxide (NO) and glutathione (GSH) and NADPH oxidase activity. Cx40 expression was determined by Western-blot.
TBI-induced brain injuries gradually increased from 6 h to 24 h post CCI, and the severity remained till 72 h. The level of oxidative stress was consistent with the extent of neurological deficits. Cx40 was upregulated after TBI in a linear correlated manner with increased oxidative stress. With NAC intervention, both neurological deficits and oxidative stress were significantly attenuated. Meanwhile, elevated Cx40 expression in cortex was also prevented by NAC treatment.
These studies revealed the relationship between levels of Cx40 and oxidative stress after TBI. The cortex Cx40 expression was positively correlated with the cerebral oxidative stress, indicating the involvement of Cx40 in the progress of brain damage.
氧化应激是创伤性脑损伤（TBI）后病理生理变化的重要因素。据报道，连接蛋白43（Cx43）会导致脑损伤。然而，连接蛋白40（Cx40）的影响尚未得到详细研究。
在本研究中，我们假设Cx40参与了TBI后氧化应激诱导的脑损伤。
将控制性皮质撞击（CCI）模型引入Wistar大鼠作为TBI模型。对TBI大鼠和N-乙酰半胱氨酸（NAC）治疗的TBI大鼠进行神经功能缺损、氧化应激和Cx40评估。采用神经严重程度评分（NSS）评估神经功能缺损。通过组织染色测量脑梗死。通过测量脑含水量评估脑水肿。收集皮质样本以测量丙二醛（MDA）、一氧化氮（NO）和谷胱甘肽（GSH）的组织水平以及NADPH氧化酶活性。通过蛋白质免疫印迹法测定Cx40表达。
TBI诱导的脑损伤在CCI后6小时至24小时逐渐增加，严重程度一直持续到72小时。氧化应激水平与神经功能缺损程度一致。TBI后Cx40上调，与氧化应激增加呈线性相关。通过NAC干预，神经功能缺损和氧化应激均显著减轻。同时，NAC治疗也阻止了皮质中Cx40表达的升高。
这些研究揭示了TBI后Cx40水平与氧化应激之间的关系。皮质Cx40表达与脑氧化应激呈正相关，表明Cx40参与了脑损伤的进展。
