LAUSR

AIMS To understand mechanisms underlying vasopressin hypersecretion in stroke and its association with brain injury, we investigated effects of blocking aquaporin 4 (AQP4) in the supraoptic nucleus (SON) on vasopressin neuronal activity and cerebral injuries in male rats of unilateral middle cerebral artery occlusion (MCAO). MAIN METHODS Establishing MCAO model without or with microinjection of TGN-020 into the SON, performing Western blots and immunohistochemistry and analyzing the expression levels and spatial distribution of functional proteins in the SON and/or the cerebral cortex. KEY FINDINGS MCAO increased plasma vasopressin levels, caused neurological damage and increased glycogen synthase kinase 3β (GSK-3β) in the SON and the cortex of MCAO side. In the SON, MCAO significantly increased c-Fos in vasopressin neurons and astrocytic somata in the ventral glial lamina. MCAO significantly reduced glial fibrillary acidic protein (GFAP) and AQP4 around vasopressin neurons, which accompanied separation of GFAP from AQP4. By contrast, blocking AQP4 by microinjection of TGN-020 into the SON blocked MCAO-evoked GSK-3β increase as well as the reduction of AQP4 relative to GFAP around vasopressin neurons in the SON. In the cortex, TGN-020 in the SON also blocked MCAO-evoked increase in GSK-3β while reduced neurological damages. SIGNIFICANCE These findings indicate that MCAO disrupts interactions of GFAP with AQP4 in astrocytic processes in the SON, which increases vasopressin neuronal activity. Blocking AQP4 in the SON can block abnormal activation of vasopressin neurons and alleviate ischemic brain injury, which provides novel targets for alleviating ischemic brain injury.