Liang Weihua, Zhang Weiwei, Zhao Shifu, Liang Hua, Zhang Jinli, Wang Luyan
No. 263 Clinic of PLA Army General Hospital, Beijing 101149, P.R. China.
Department of Neurology, Xinqiao Hospital, The Third Military Medical University, Chongqing 400038, P.R. China.
Exp Ther Med. 2017 May;13(5):2468-2472. doi: 10.3892/etm.2017.4228. Epub 2017 Mar 14.
Myelinated axons require the correct localization of key proteins that are essential for nerve conduction and cognitive function. Little is known regarding the altered expression of contactin-associated protein 2 (Caspr2) at the juxtaparanodal regions and Nav1.6 at the node of Ranvier in response to chronic cerebral hypoperfusion (CCH). The aim of the present study was to examine the alterations in the key protein of myelinated axons and the potential mechanisms that may follow CCH. We established a rat model of CCH by controllable partial narrowing of bilateral common carotid arteries. Then, we detected cerebral blood flow (CBF) after surgery. We also evaluated motor-evoked potentials (MEPs), assessed the Morris water maze test, analyzed Caspr2 expression through immunohistochemistry and Nav1.6 protein expression through western blot analysis at 2, 4 and 12 weeks. The results revealed that the mean CBF value was significantly decreased to 33.90±5.48%. The MEP latencies and the escaping latencies were significantly prolonged. There was also an elongation of the first time passing of the hidden platform with a reduction of crossing platform times in spatial probing. Furthermore, the Caspr2 immunoreactivity demonstrated that the Caspr2 level was significantly downregulated with abnormal locations in the corpus callosum. The western blot analysis of Nav1.6 protein revealed that the level was reduced significantly over time. The results demonstrate that CCH leads to central conductive function loss, cognitive function damage and alterations in the key protein of myelinated axons, which may provide a molecular basis and key link for white matter damage.
有髓轴突需要关键蛋白正确定位，这些蛋白对神经传导和认知功能至关重要。关于慢性脑灌注不足（CCH）时，紧密连接相关蛋白2（Caspr2）在近节旁区的表达改变以及郎飞结处Nav1.6的表达改变，目前所知甚少。本研究的目的是检查有髓轴突关键蛋白的变化以及CCH可能引发的潜在机制。我们通过可控性部分缩窄双侧颈总动脉建立了CCH大鼠模型。然后，我们在术后检测了脑血流量（CBF）。我们还评估了运动诱发电位（MEP），进行了莫里斯水迷宫试验，在2周、4周和12周时通过免疫组织化学分析了Caspr2表达，并通过蛋白质免疫印迹分析了Nav1.6蛋白表达。结果显示，平均CBF值显著降低至33.90±5.48%。MEP潜伏期和逃避潜伏期显著延长。在空间探索中，隐藏平台的首次通过时间延长，穿越平台次数减少。此外，Caspr2免疫反应性表明，胼胝体中Caspr2水平显著下调且位置异常。Nav1.6蛋白的蛋白质免疫印迹分析显示，随着时间推移其水平显著降低。结果表明，CCH导致中枢传导功能丧失、认知功能损害以及有髓轴突关键蛋白的改变，这可能为白质损伤提供分子基础和关键环节。
