Hypidone hydrochloride(YL-0919)ameliorates functional deficits after traumatic brain injury in mice by activating the sigma-1 receptor for antioxidation  

作　　者：Yafan Bai Hui Ma Yue Zhang Jinfeng Li Xiaojuan Hou Yixin Yang Guyan Wang Yunfeng Li 

机构地区：[1]Department of Anesthesiology,Beijing Tongren Hospital,Capital Medical University,Beijing,China [2]Beijing Institute of Basic Medical Sciences,Beijing,China [3]Hebei North University,Zhangjiakou,Hebei Province,China [4]Beijing Institute of Pharmacology and Toxicology,State Key Laboratory of Toxicology and Medical Countermeasures,Beijing Key Laboratory of Neuropsychopharmacology,Beijing,China

出　　处：《Neural Regeneration Research》2025年第8期2325-2336,共12页中国神经再生研究（英文版）

基　　金：supported by the National Natural Science Foundation of China,Nos.82204360(to HM)and 82270411(to GW);National Science and Technology Innovation 2030 Major Program,No.2021ZD0200900(to YL)。

摘　　要：Traumatic brain injury involves complex pathophysiological mechanisms,among which oxidative stress significantly contributes to the occurrence of secondary injury.In this study,we evaluated hypidone hydrochloride(YL-0919),a self-developed antidepressant with selective sigma-1 receptor agonist properties,and its associated mechanisms and targets in traumatic brain injury.Behavioral experiments to assess functional deficits were followed by assessment of neuronal damage through histological analyses and examination of blood-brain barrier permeability and brain edema.Next,we investigated the antioxidative effects of YL-0919 by assessing the levels of traditional markers of oxidative stress in vivo in mice and in vitro in HT22 cells.Finally,the targeted action of YL-0919 was verified by employing a sigma-1 receptor antagonist(BD-1047).Our findings demonstrated that YL-0919 markedly improved deficits in motor function and spatial cognition on day 3 post traumatic brain injury,while also decreasing neuronal mortality and reversing blood-brain barrier disruption and brain edema.Furthermore,YL-0919 effectively combated oxidative stress both in vivo and in vitro.The protective effects of YL-0919 were partially inhibited by BD-1047.These results indicated that YL-0919 relieved impairments in motor and spatial cognition by restraining oxidative stress,a neuroprotective effect that was partially reversed by the sigma-1 receptor antagonist BD-1047.YL-0919 may have potential as a new treatment for traumatic brain injury.

关 键 词：antidepressant drug blood-brain barrier cognitive function hypidone hydrochloride(YL-0919) neurological function nuclear factor-erythroid 2 related factor 2 oxidative stress sigma-1 receptor superoxide dismutase traumatic brain injury 

分 类 号：R651.15[医药卫生—外科学]