Department of Neurosurgery, the Second Hospital of Hebei Medical University, No.215, Heping Road, Shijiazhuang, 050000, Hebei, China.
Department of Doppler Ultrasound, the Second Hospital of Hebei Medical University, No.215, Heping Road, Shijiazhuang, 050000, Hebei, China.
Neurochem Res. 2021 Jun;46(6):1380-1389. doi: 10.1007/s11064-021-03272-7. Epub 2021 Mar 2.
Traumatic brain injury (TBI) has been a crucial health problem, with more than 50 million patients worldwide each year. Glymphatic system is a fluid exchange system that relies on the polarized water channel aquaporin-4 (AQP4) at the astrocytes, accounting for the clearance of abnormal proteins and metabolites from brain tissues. However, the dysfunction of glymphatic system and alteration of AQP4 polarization during the progression of TBI remain unclear. AQP4 and Wild Type (WT) mice were used to establish the TBI mouse model respectively. Brain edema and Evans blue extravasation were conducted 24 h post-injury to evaluate the acute TBI. Morris water maze (MWM) was used to establish the long-term cognitive functions of AQP4 and WT mice post TBI. Western-blot and qRT-PCR assays were performed to demonstrate protective effects of AQP4 deficiency to blood-brain barrier (BBB) integrity and amyloid-β clearance. The inflammation of cerebral tissues post TBI was estimated by ELISA assay. AQP4 deficiency alleviated the brain edema and neurological deficit in TBI mice. AQP4-knockout led to improved cognitive outcomes in mice post TBI. The BBB integrity and cerebral amyloid-β clearance were protected by AQP4 deficiency in TBI mice. AQP4 deficiency ameliorated the TBI-induced inflammation. AQP4 deficiency improved longer-term neurological outcomes in a mouse model of TBI.
创伤性脑损伤（TBI）一直是一个重要的健康问题，全球每年有超过 5000 万患者。 糖质新生系统是一种依赖星形胶质细胞上的极性水通道水通道蛋白-4（AQP4）的液体交换系统，负责清除脑组织中的异常蛋白质和代谢物。然而，在 TBI 进展过程中糖质新生系统的功能障碍和 AQP4 极化的改变尚不清楚。分别使用 AQP4 和野生型（WT）小鼠建立 TBI 小鼠模型。脑水肿和 Evans 蓝外渗在损伤后 24 小时进行，以评估急性 TBI。Morris 水迷宫（MWM）用于建立 TBI 后 AQP4 和 WT 小鼠的长期认知功能。Western-blot 和 qRT-PCR 测定用于证明 AQP4 缺乏对血脑屏障（BBB）完整性和淀粉样β清除的保护作用。ELISA 测定估计 TBI 后脑组织的炎症。AQP4 缺乏减轻 TBI 小鼠的脑水肿和神经功能缺损。AQP4 敲除导致 TBI 后小鼠的认知结果得到改善。AQP4 缺乏在 TBI 小鼠中保护 BBB 完整性和脑淀粉样β清除。AQP4 缺乏减轻 TBI 诱导的炎症。AQP4 缺乏改善 TBI 小鼠的长期神经学结局。
