ASN Neuro ( IF 4.7 ) Pub Date : 2020-09-26 , DOI: 10.1177/1759091420960550 Dan Cui 1 , Shuwei Jia 1 , Jiawei Yu 1 , Dongyang Li 1 , Tong Li 1 , Yang Liu 1 , Jinlong Chang 2 , Xiaoran Wang 1 , Xiaoyu Liu 1 , Yu-Feng Wang 1
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.
中文翻译:
抑制视上核水通道蛋白4减轻脑中动脉闭塞大鼠脑梗死
在缺血性中风中,血管加压素分泌过多是脑肿胀和脑损伤的关键因素。为了阐明缺血性中风诱发的血管加压素分泌过多的神经机制,我们观察了大鼠单侧永久性大脑中动脉闭塞 (MCAO) 对视上核 (SON) 星形胶质细胞可塑性和加压素神经元活动及其相关脑损伤的影响。MCAO 8 小时导致 MCAO 侧脑梗塞,其中水含量也增加。免疫组化检查显示MCAO侧SON中磷酸化细胞外信号调节蛋白激酶1/2(pERK1/2)阳性加压素神经元的百分比显着高于非MCAO侧和假手术组。在皮质中,pERK1/2 和水通道蛋白 4 的表达在梗死区显着增加,而胶质纤维酸性蛋白 (GFAP) 与脑皮质的非梗死侧相比显着降低。将 N-(1,3,4-噻二唑基)烟酰胺-020 [TGN-020,一种特定的水通道蛋白 4 阻滞剂] 显微注射到 SON 中,可阻止 MCAO 诱发的 SON 中 pERK1/2 的增加以及 GFAP 的减少以及皮层梗死区 pERK1/2 和水通道蛋白 4 的增加。最后,氧气和葡萄糖剥夺降低了 GFAP 表达以及 GFAP 与脑切片 SON 中水通道蛋白 4 的共定位和分子关联。这些作用被 TGN-020 和/或根皮素(一种星形胶质细胞体积调节阴离子通道的阻滞剂)阻断。