文献类型：期刊文献

英文题名：Stage-specific targeting of the GABAergic system in ischemic stroke: mechanisms and therapeutic strategies

作者：Zhang, Lei[1];Liu, Cui[1];Wen, Yujie[1];Wei, Long[1];Li, Xing[1];Guo, Wanquan[1];Hu, Miaomiao[1];Du, Xiaozheng[1,2]

第一作者：张磊;张雷

通信作者：Du, XZ[1]

机构：[1]Gansu Univ Chinese Med, Coll Acupuncture & Tuina, Lanzhou 730000, Gansu, Peoples R China;[2]Gansu Univ Chinese Med, Dept Acupuncture & Tuina, 35 Dingxi East Rd, Lanzhou 730000, Gansu, Peoples R China

第一机构：甘肃中医药大学

通信机构：[1]corresponding author), Gansu Univ Chinese Med, Dept Acupuncture & Tuina, 35 Dingxi East Rd, Lanzhou 730000, Gansu, Peoples R China.|[10735]甘肃中医药大学;

年份：2026

卷号：230

外文期刊名：NEUROBIOLOGY OF DISEASE

收录：;Scopus(收录号：2-s2.0-105051655371);WOS:【SCI-EXPANDED(收录号:WOS:001890871000001)】；

基金：This work was supported by the Gansu Province Key Traditional Chinese Medicine Research Project (GZKZ-2024-35) , National Natural Science Foundation of China (No.82460965) .

语种：英文

外文关键词：ischemic stroke; GABAergic signaling; tonic inhibition; chloride homeostasis; GABA transporters; post-stroke neural plasticity

摘要：Neural injury and functional recovery after ischemic stroke are strongly time dependent. The acute phase is dominated by energy failure, ionic disequilibrium, excitotoxicity, spreading depolarization, and amplification of inflammation; the subacute phase is characterized by progressive network reorganization and competing forms of plasticity; and the chronic phase predominantly involves adaptive remodeling of residual networks. As the principal inhibitory neurotransmitter system in the central nervous system, gamma-aminobutyric acid (GABA) does not exert uniformly protective or detrimental effects throughout the course of stroke. Instead, its effects are jointly determined by intervention timing, the cellular source of GABA, receptor subtype and synaptic or extrasynaptic localization, transporter and metabolic status, and chloride homeostasis. After summarizing GABA synthesis and metabolism, receptors, transporters, and chloride homeostasis, this review follows the temporal course of ischemic stroke to discuss the protective effects of GABAergic inhibition against excitotoxicity and neuroinflammation during the acute phase, the bidirectional effects of GABA and tonic inhibition during the subacute phase, and the relationships among GABAergic tone, intrahemispheric and interhemispheric network reorganization, and windows of plasticity during the chronic phase. We further summarize preclinical and clinical evidence for receptor modulators, agents targeting GABA or chloride transport, monoamine oxidase B inhibitors, and non-invasive brain stimulation. We emphasize that effective targeting of the GABAergic system requires modulation tailored to disease phase, cellular source, receptor subtype, and spatial context, rather than indiscriminate enhancement or suppression of GABAergic signaling.