蛛网膜下腔出血后突触转换致神经血管耦联反转的作用和机制研究
结题报告
批准号:
81960226
项目类别:
地区科学基金项目
资助金额:
33.7 万元
负责人:
王飞
依托单位:
学科分类:
脑血管结构、功能异常及相关疾病
结题年份:
2023
批准年份:
2019
项目状态:
已结题
项目参与者:
王飞
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中文摘要
蛛网膜下腔出血(SAH)后神经血管耦联(NVC)使脑微循环反常性收缩,即NVC反转可致脑血流下降并与SAH预后密切相关。NVC反转治疗意义大但发生机制不明。我们前期研究发现:SAH后胚胎期谷氨酸(Glu)/γ-氨基丁酸(GABA)突触选择信号激活、皮层GABA突触数量和信号传递功能上调并且阻滞GABA突触可逆转NVC反转。故提出假设:胚胎期突触选择信号可对SAH产生响应并引起NVC环路中Glu突触向GABA转换,继而导致NVC反转和脑微循环障碍。为论证之,通过研究SAH大鼠或脑片的突触分子标志及电信号传递、脑微循环形态和血流灌注及其壁细胞兴奋性等,首先证实SAH可引起Glu/GABA突触转换,再明确突触转换与NVC反转和微循环障碍的因果关系,最后阐明胚胎期Glu/GABA突触选择信号在上述作用中的分子机制。从神经环路角度对SAH后脑微循环障碍做出解析,为其研究及干预提供理论创新和实践指导。
英文摘要
Neurovascular coupling (NVC) microcircuit plays an essential role to ensure sufficient cerebral perfusion during increased neuronal activities via dilating cerebral microcirculation. NVC inversion, defined as paradoxical microcirculation constriction, was only found in rodent models of subarachnoid hemorrhage. Additionally, NVC inversion has been shown to be related to microcirculation dysfunction and impaired cerebral perfusion after SAH. Therefore, NVC inversion is one of the determinants to SAH outcome, however, the underlying pathogenesis remains unclear. Glutamatergic (Glu) synapses are the central entity in intact NVC microcircuit that may be altered by SAH, resulting in NVC inversion. Our preliminary data showed that embryonic Glu/γ-aminobutyric acid (GABA) synapse selector responded to SAH, and reduction of Glu synapses was accompanied by GABA synapses elevation in cerebral cortex. Further, NVC inversion was almost completely reversed when GABA synapses were blocked pharmacologically. These preliminary data led us to hypothesize that synapse switching from Glu to GABA via embryonic Glu/GABA synapse selector results in NVC inversion following SAH. We will be testing this hypothesis comprehensively by studying synapse proteins and electrophysiology, microcirculation morphology, and cerebral perfusion after SAH. This project will provide information concerning Glu/GABA synapse switching after SAH. Furthermore, the pathogenic role of synapse switching in NVC inversion and microcirculation dysfunction after SAH will also be evaluated. Lastly, we ought to elucidate the molecular role of embryonic Glu/GABA synapse selector in synapse switching after SAH. Endpoints of this project would possibly connect the pathological NVC to microcirculation dysfunction following SAH and provide a novel target for research and clinical management of impaired cerebral perfusion following SAH.
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DOI:10.3791/65872
发表时间:2023-09-01
期刊:JOVE-JOURNAL OF VISUALIZED EXPERIMENTS
影响因子:1.2
作者:Deng,Hong-Ji;Wu,Kun;Wang,Fei
通讯作者:Wang,Fei
DOI:10.3760/cma.j.cn115354-20220520-00353
发表时间:2022
期刊:中华神经医学杂志
影响因子:--
作者:李云聪;张永进;王飞
通讯作者:王飞
DOI:10.16557/j.cnki.1000-7547.2023.04.020
发表时间:2023
期刊:神经解剖学杂志
影响因子:--
作者:李贵博;周磊;王飞
通讯作者:王飞
Endocrine Dysfunction Following Stroke
中风后内分泌功能障碍
DOI:10.1007/s11481-020-09935-6
发表时间:2020-07
期刊:Journal of Neuroimmune Pharmacology
影响因子:6.2
作者:Wang Fei;Luo Ming-ying;Zhou Lei;Yang Li;Lanzino Giuseppe;Chan Heng-Jui;Wellman George C.
通讯作者:Wellman George C.
DOI:10.3791/65873
发表时间:2023
期刊:Journal of Visualized Experiments
影响因子:--
作者:Yong-Jin Zhang;Yun-Cong Li;Han-Fu Yu;Chong Li;Hong-Ji Deng;Yue-Hong Dong;Gui-Bo Li;Fei Wang
通讯作者:Fei Wang
平滑肌源性ATP-P2X1/X4在蛛网膜下腔出血后的调节反应及其在脑血管痉挛中的作用机制
  • 批准号:
    81760223
  • 项目类别:
    地区科学基金项目
  • 资助金额:
    34.0万元
  • 批准年份:
    2017
  • 负责人:
    王飞
  • 依托单位:
CaV2.3在蛛网膜下腔出血后表达的调控机制及其在脑血管痉挛中的作用机理
  • 批准号:
    81260182
  • 项目类别:
    地区科学基金项目
  • 资助金额:
    49.0万元
  • 批准年份:
    2012
  • 负责人:
    王飞
  • 依托单位:
国内基金
海外基金