Zhu Juan, Mo Jiaying, Liu Kewei, Chen Quanfeng, Li Zheqi, He Yihua, Chang Yuan, Lin Chuman, Yu Mingjia, Xu Yikai, Tan Xiangliang, Huang Kaibin, Pan Suyue
Departments of Neurology (J.Z., K.L., Q.C., Z.L., Y.H., Y.C., C.L., M.Y., K.H., S.P.), Nanfang Hospital, Southern Medical University, Guangzhou, Guangdong, China.
Medical Imaging Center (J.M., Y.X., X.T.), Nanfang Hospital, Southern Medical University, Guangzhou, Guangdong, China.
Stroke. 2024 May;55(5):1393-1404. doi: 10.1161/STROKEAHA.123.045941. Epub 2024 Mar 27.
Blood-brain barrier damage has traditionally been considered to determine the occurrence and development of poststroke brain edema, a devastating and life-threatening complication. However, no treatment strategy targeting blood-brain barrier damage has been proven clinically effective in ameliorating brain edema.
In mice with stroke models induced by transient middle cerebral artery occlusion (MCAO), the changes in glymphatic system (GS) function impairment were detected by ex vivo fluorescence imaging, 2-photon in vivo imaging, and magnetic resonance imaging within 1 week after MCAO, and the effects of GS impairment and recovery on the formation and resolution of brain edema were evaluated. In addition, in patients with ischemic stroke within 1 week after onset, changes in GS function and brain edema were also observed by magnetic resonance imaging.
We found that the extravasation of protein-rich fluids into the brain was not temporally correlated with edema formation after MCAO in mice, as brain edema reabsorption preceded blood-brain barrier closure. Strikingly, the time course of edema progression matched well with the GS dysfunction after MCAO. Pharmacological enhancement of the GS function significantly alleviated brain edema developed on day 2 after MCAO, accompanied by less deposition of Aβ (amyloid-β) and better cognitive function. Conversely, functional suppression of the GS delayed the absorption of brain edema on day 7 after MCAO. Moreover, patients with ischemic stroke revealed a consistent trend of GS dysfunction after reperfusion as MCAO mice, which was correlated with the severity of brain edema and functional outcomes.
GS is a key contributor to the formation of brain edema after ischemic stroke, and targeting the GS may be a promising strategy for treating brain edema in ischemic stroke.
URL: https://www.chictr.org.cn/showproj.html?proj=162857; Unique identifier: NFEC-2019-189.
血脑屏障损伤传统上被认为决定了中风后脑水肿的发生和发展，这是一种具有破坏性且危及生命的并发症。然而，尚无针对血脑屏障损伤的治疗策略在临床上被证明对减轻脑水肿有效。
在通过短暂性大脑中动脉闭塞（MCAO）诱导的中风模型小鼠中，在MCAO后1周内通过离体荧光成像、双光子体内成像和磁共振成像检测淋巴系统（GS）功能损伤的变化，并评估GS损伤和恢复对脑水肿形成和消退的影响。此外，在发病后1周内的缺血性中风患者中，也通过磁共振成像观察GS功能和脑水肿的变化。
我们发现，富含蛋白质的液体渗入大脑与小鼠MCAO后的水肿形成在时间上不相关，因为脑水肿的重吸收先于血脑屏障的闭合。令人惊讶的是，水肿进展的时间进程与MCAO后的GS功能障碍非常匹配。GS功能的药理学增强显著减轻了MCAO后第2天出现的脑水肿，同时伴有较少的β淀粉样蛋白（Aβ）沉积和更好的认知功能。相反，GS的功能抑制延迟了MCAO后第7天脑水肿的吸收。此外，缺血性中风患者在再灌注后显示出与MCAO小鼠一致的GS功能障碍趋势，这与脑水肿的严重程度和功能结果相关。
GS是缺血性中风后脑水肿形成的关键因素，针对GS可能是治疗缺血性中风脑水肿的一种有前景的策略。
网址：https://www.chictr.org.cn/showproj.html?proj=162857；唯一标识符：NFEC-2019-189。
