Hou Chunmei, Chen Guichuan, Li Di, Wang Xiaoran, Liu Xiaoyu, Cui Dan, Jiang Yunhao, Liu Yang, Wang Ping, Wang Yu-Feng, Meng Dexin, Jia Shuwei
Department of Physiology, School of Basic Medical Sciences, Harbin Medical University, Harbin, China.
Department of Medicine, Ziyang College of Dental Technology, Ziyang, China.
Neuroendocrinology. 2024;114(12):1090-1111. doi: 10.1159/000541648. Epub 2024 Sep 30.
Cerebral swelling and brain injury in ischemic stroke are closely related to increased vasopressin (VP) secretion. How to alleviate ischemic brain injury by suppressing VP hypersecretion through simply available approaches remains to be established.
Using a rat model of middle cerebral artery occlusion (MCAO), testing effects of the intranasal application of low concentration saline-0.09% NaCl (IAL) on brain damage, VP neuronal activity, synaptic inputs, astrocytic plasticity, and olfactory bulb (OB) activity in immunohistochemistry, patch-clamp recording, Western blotting, and co-immunoprecipitation.
IAL reduced MCAO-evoked neurological disorders, brain swelling, injury and loss of neurons, increase in c-Fos expression, and excitation of supraoptic VP neurons. The effects of IAL on VP neurons were associated with its suppression of MCAO-evoked increase in the frequency of excitatory synaptic inputs and decrease in the expression of glial fibrillary acidic protein (GFAP) filaments around VP neurons. MCAO and IAL also caused similar but weaker reactions in putative oxytocin neurons. In the OB, MCAO increased the firing rate of mitral cells on the MCAO side, which was reduced by IAL. A direct hypotonic challenge of OB slices increased the expression of glutamine synthetase and GFAP filaments in the glomerular bodies while reducing the firing rate of mitral cells. Blocking aquaporin 4 activity in the supraoptic and paraventricular nuclei on the MCAO side reduced MCAO-evoked VP increase and brain damage.
IAL reduces ischemic stroke-evoked brain injury in association with suppression of VP neuronal activity through reducing excitatory synaptic inputs and astrocytic process retraction, which likely result from reducing mitral cell activation in ischemic side.
缺血性中风中的脑肿胀和脑损伤与血管加压素（VP）分泌增加密切相关。如何通过简单可行的方法抑制VP分泌过多来减轻缺血性脑损伤仍有待确定。
使用大脑中动脉闭塞（MCAO）大鼠模型，通过免疫组织化学、膜片钳记录、蛋白质免疫印迹和免疫共沉淀技术，测试鼻内应用低浓度盐水-0.09%氯化钠（IAL）对脑损伤、VP神经元活动、突触输入、星形胶质细胞可塑性和嗅球（OB）活动的影响。
IAL减轻了MCAO诱发的神经功能障碍、脑肿胀、神经元损伤和丢失、c-Fos表达增加以及视上核VP神经元的兴奋。IAL对VP神经元的作用与其抑制MCAO诱发的兴奋性突触输入频率增加以及VP神经元周围胶质纤维酸性蛋白（GFAP）丝表达减少有关。MCAO和IAL在假定的催产素神经元中也引起了相似但较弱的反应。在OB中，MCAO增加了MCAO侧二尖瓣细胞的放电频率，而IAL降低了该频率。对OB切片进行直接低渗刺激增加了肾小球体中谷氨酰胺合成酶和GFAP丝的表达，同时降低了二尖瓣细胞的放电频率。阻断MCAO侧视上核和室旁核中的水通道蛋白4活性可减少MCAO诱发的VP增加和脑损伤。
IAL通过减少兴奋性突触输入和星形胶质细胞回缩来抑制VP神经元活动，从而减轻缺血性中风诱发的脑损伤，这可能是由于减少了缺血侧二尖瓣细胞的激活所致。
