Angiotensin II type 1 receptor deficiency protects against the impairment of blood–brain barrier in a mouse model of traumatic brain injury.

Aquaporin 4 (AQP4), usually expressed at astrocytes end-feet, is a main component of the lymph-lymphatic system and promotes paravascular cerebrospinal fluid-interstitial fluid exchange. Moreover, angiotensin II type 1 (AT1) receptor affects amyloid β (Aβ) levels. This study aimed to detect the effect of AT1 receptor deficiency on the blood-brain barrier (BBB) of traumatic brain injury (TBI) mice and the effect on Aβ level and glial lymphatic circulation. TBI model was built using AT1 receptor knockout mice (AT1-KO) and C57BL/6 mice (wild type, WT). BBB integrity was detected by Evans blue extravasation. The expression of the astrocytic water channel AQP4 and astrocyte activation were evaluated with immunofluorescence. The expressions of amyloid precursor protein (APP), junction protein zonula occludens protein-1 (ZO-1) and occludin in mice brain were detected by Western blot (WB). Aβ levels were assayed by enzyme-linked immunosorbent assay (ELISA). AT1 receptor deficiency defended BBB integrity and rescued occludin and ZO-1 decrease in mice brain induced by TBI. AT1-KO mice had less increase of APP expression and Aβ 1–42, Aβ 1–40 levels compared to WT mice under TBI. Moreover, AT1 receptor deficiency was found to significantly inhibit AQP4 depolarization after TBI. T1 receptor deficiency attenuated TBI-induced impairments of BBB by rescuing tight junction proteins and inhibited AQP4 polarization, thus improving the function of glymphatic system to enhance interstitial Aβ clearance in TBI mice brain. [ABSTRACT FROM AUTHOR]