Alleviation of Cerebral Infarction of Rats With Middle Cerebral Artery Occlusion by Inhibition of Aquaporin 4 in the Supraoptic Nucleus.

Abstract

In ischemic stroke, vasopressin hypersecretion is a critical factor of cerebral swelling and brain injury. To clarify neural mechanisms underlying ischemic stroke-evoked vasopressin hypersecretion, we observed the effect of unilateral permanent middle cerebral artery occlusion (MCAO) in rats on astrocytic plasticity and vasopressin neuronal activity in the supraoptic nucleus (SON) as well as their associated cerebral injuries. MCAO for 8 hr caused cerebral infarction in the MCAO side where water contents also increased. Immunohistochemical examination revealed that the percentage of phosphorylated extracellular signal-regulated protein kinase 1/2 (pERK1/2)-positive vasopressin neurons in the SON of MCAO side was significantly higher than that in non-MCAO side and in sham group. In the cortex, pERK1/2 and aquaporin 4 expressions increased significantly in the infarction area, while glial fibrillary acidic protein (GFAP) reduced significantly compared with the noninfarction side in brain cortex. Microinjection of N-(1,3,4-Thiadiazolyl)nicotinamide-020 [TGN-020, a specific blocker of aquaporin 4] into the SON blocked MCAO-evoked increases in pERK1/2 in the SON as well as the reduction of GFAP and the increase in pERK1/2 and aquaporin 4 in the infarction area of the cortex. Finally, oxygen and glucose deprivation reduced GFAP expression and the colocalization and molecular association of GFAP with aquaporin 4 in the SON in brain slices. These effects were blocked by TGN-020 and/or phloretin, a blocker of astrocytic volume-regulated anion channels. These findings indicate that blocking aquaporin 4 in the SON may reduce the activation of vasopressin neurons and brain injuries elicited by vasopressin during ischemic stroke.

• Authors: Dan Cui, Shuwei Jia, Jiawei Yu, Dongyang Li, Tong Li, Yang Liu, Jinlong Chang, Xiaoran Wang, Xiaoyu Liu, Yu-Feng Wang
• Journal: ASN neuro (ASN Neuro) 2020 Jan-Dec Vol. 12 Pg. 1759091420960550 ISSN: 1759-0914 [Electronic] United States
• PMID: 32985231 (Publication Type: Journal Article, Research Support, Non-U.S. Gov't)

Chemical References

• 2-(nicotinamide)-1,3,4-thiadiazole
• Aqp4 protein, rat
• Aquaporin 4
• Thiadiazoles
• Niacinamide

Topics

• Animals
• Aquaporin 4 (antagonists & inhibitors, metabolism)
• Infarction, Middle Cerebral Artery (metabolism)
• MAP Kinase Signaling System (drug effects, physiology)
• Male
• Microinjections (methods)
• Niacinamide (administration & dosage, analogs & derivatives)
• Rats
• Rats, Wistar
• Supraoptic Nucleus (drug effects, metabolism, pathology)
• Thiadiazoles (administration & dosage)