Abstract WP27: Tissue Kallikrein Attenuates Ischemic Edema by Increasing Water Transport Function of AQP4 in Glymphatic System in pMCAO Mice

Abstract

Aquaporin-4 (AQP4) is an essential water channel protein in GS (glymphatic system), and is widely distributed in astrocytes at the brain/cerebrospinal fluid interface, where it facilitates water movement. Altered AQP4 polarization and expression are evident in cytotoxic edema in pMCAO mice in our previous study, glymphatic MRI of which also shows reduced CSF tracer entry and clearance. Tissue Kallikrein treatment provides cerebral infarction patients with vasodilatory activity, which may facilitate the dynamics of CSF in GS. We hypothesized that TK could attenuate depolarization of AQP4 to confer benefit in brain edema by boosting the kinetics in GS. In this study, we evaluated the effects of TK on mice acute ischemic edema in both wild and AQP4-/- pMCAO models. A fluorescent tracer was injected into the striatum of both mice, and the infusion pattern of the fluorescent tracer in the brain parenchyma was detected to confirm the function of AQP4 in alleviating edema by TK. Concurrently, immunohistochemistry analysis was performed to explore the altered AQP4 polarization and expression in TK treatment animals. Our results indicated that TK attenuated brain edema was associated with improved transport function of AQP4 to CSF in pMCAO mice, which might relate to the alteration of polarization and expression of AQP4.