Impaired Glymphatic Transport Kinetics Following Induced Acute Ischemic Brain Edema in a Mouse pMCAO Model

作者：Jianying Zhang, Hongchen Zhao, Xue Yang, Yiqi Liu, Guohang Fan, He Wang, Qiang Dong, Wenjie Cao · 发表于：Frontiers in Neurology · 年份：2022 · DOI：10.3389/fneur.2022.860255 · 被引用次数：30 · 研究领域：Cerebrospinal fluid and hydrocephalus、Spinal Dysraphism and Malformations、Fetal and Pediatric Neurological Disorders

Background: Cerebral edema forms immediately after blood flow interruption in ischemic stroke, which largely increased the death and disability. The glymphatic (glial-lymphatic) pathway is a major regulator of the brain liquid dynamics and homeostasis. This study aimed to investigate the transport kinetics of the glymphatic system after the appearance of ischemic edema. Methods: In this study, a coated filament was attached to the left middle cerebral artery (MCA) of mice to establish a mouse model of permanent middle cerebral artery occlusion with an intact blood-brain barrier (BBB). The glymphatic function was then quantified using contrast-enhanced MRI (11.7T) by employing an injection of gadobenate dimeglumine (BOPTA-Gd) into the cisterna magna of mice. We then evaluated the expression and polarization of aquaporin-4 (AQP4) as a proxy for the physiological state of the glymphatic system. Results: Our results revealed a positive correlation between the signal intensity in T1-weighted images and the corresponding apparent diffusion coefficient (ADC) values in the cortex, striatum, and periventricular zone, suggesting that impaired glymphatic transport kinetics in these regions is correlated to the cytotoxic edema induced by the occlusion of MCA. Furthermore, the increased depolarization of AQP4 in the parenchyma perivascular space (PVS) was consistent with glymphatic failure following the induced early cerebral ischemic edema. Conclusions: Glymphatic transport kinetics were...