Arginine-Vasopressin V-1 but not V-2 Receptor Antagonism Modulates Infarct Volume, Brain Water Content, and Aquaporin-4 Expression Following Experimental Stroke

作者：Liu Xiaoqin; Nakayama Shin; Amiry Moghaddam Mahmood; Ottersen Ole Petter; Bhardwaj Anish^*

来源：Neurocritical Care, 2010, 12(1): 124-131.

DOI：10.1007/s12028-009-9277-x

• Aquaporins
• Stroke
• Focal cerebral ischemia
• Infarct
• Cerebral edema
• Arginine-vasopressin

Background Aquaporin-4 (AQP4) plays an important role in the evolution of ischemia-evoked cerebral edema. Experimental studies have also demonstrated anti-edema effects of arginine-vasopressin (AVP) antagonists. In a well-characterized murine model of ischemic stroke, we tested the hypotheses that treatment with selective AVP V-1 but not V-2 receptor antagonist (1) attenuates injury volume and ischemia-evoked cerebral edema; and (2) modulates ischemia-evoked AQP4 expression.
Methods Isoflurane-anesthetized adult male C57bl/6 mice were subjected to 60 min of middle cerebral artery occlusion (MCAO) by the intraluminal suture technique. Adequacy of MCAO and reperfusion was monitored with laser-Doppler flowmetry over the ipsilateral parietal cortex. Mice were treated with intracerebroventricular injection of selective AVP V-1 and V-2 receptor antagonist or control vehicle (0.9% saline). Infarct volume (tetrazolium staining), cerebral edema (wet-to-dry ratios) and AQP4 protein expression (immunoblotting) were determined in different treatment groups in separate sets of experiments at 24 h of reperfusion.
Results Infarct volume (percentage of contralateral structure; mean +/- SEM) was significantly attenuated in mice treated with 500 ng V-1 receptor antagonist as well as at a dose of 1000 ng compared to controls. However, there was no difference in infarct volume following treatment with 1000 ng V-2 antagonist as compared to controls. Water content in the ischemic hemisphere was significantly attenuated with V-1 receptor antagonist (1000 ng) but not with V-2 receptor antagonist as compared to controls. Treatment with AVP V-1 receptor antagonist (1000 ng) but not V-2 receptor antagonist, significantly upregulated AQP4 protein expression (% beta-actin) compared to saline-treated mice in ipsilateral (ischemic) cerebral cortex.
Conclusions These data demonstrate that following experimental stroke AVP V-1 receptor antagonism: (1) attenuates injury volume and ischemia-evoked cerebral edema; (2) modulates AQP4 expression; and (3) may serve as an important therapeutic target for neuroprotection and ischemia-evoked cerebral edema.

• 出版日期2010-2
• 单位南京医科大学