个人科研网厅 | | 帮助
高级检索
当前位置： 首页 > 详情页

Delayed recanalization reduced neuronal apoptosis and neurological deficits by enhancing liver-derived trefoil factor 3-mediated neuroprotection via LINGO2/EGFR/Src signaling pathway after middle cerebral artery occlusion in rats

| 导出 | |

文献详情

资源类型：
WOS体系：
Pubmed体系：

收录情况： ◇ SCIE

作者：
Li Dujuan[1,2] * ; Lian Lifei[3] * ; Huang Lei[2,4] ; Gamdzyk Marcin[2] ; Huang Yi[2] ; Doycheva Desislava[2] ; Li Gaigai[2,3] ; Yu Shufeng[2] ; Guo Yong[2,5] ; Kang Ruiqing[2] ; Tang Hong[2] ; Tang Jiping[2] ; Kong Lingfei[1,*1] ; Zhang John H[2,4,*2] ;
单位： [1]Department of Pathology, Henan Provincial People’s Hospital (People’s Hospital of Zhengzhou University, People’s Hospital of Henan University), Zhengzhou 450003, [2]Department of Physiology and Pharmacology, Loma Linda University, Loma Linda, CA 92354, USA [3]Department of Neurology, Tongji Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan 430030, China [4]Department of Neurosurgery, Loma Linda University, Loma Linda, CA 92354, USA [5]Department of Neurosurgery, Henan Provincial People’s Hospital, Zhengzhou 450003, China
出处：
DOI： 10.1016/j.expneurol.2023.114607
ISSN：

关键词： Ischemic stroke Middle cerebral artery occlusion Apoptosis Delayed recanalization TFF3 LINGO2

摘要：
Delayed recanalization at days or weeks beyond the therapeutic window was shown to improve functional outcomes in acute ischemic stroke (AIS) patients. However, the underlying mechanisms remain unclear. Previous preclinical study reported that trefoil factor 3 (TFF3) was secreted by liver after cerebral ischemia and acted a distant neuroprotective factor. Here, we investigated the liver-derived TFF3-mediated neuroprotective mechanism enhanced by delayed recanalization after AIS. A total of 327 male Sprague-Dawley rats and the model of middle cerebral artery occlusion (MCAO) with permanent occlusion (pMCAO) or with delayed recanalization at 3 d post-occlusion (rMCAO) were used. Partial hepatectomy was performed within 5 min after MCAO. Leucine-rich repeat and immunoglobulin-like domain-containing nogo receptor-interacting protein 2 (LINGO2) siRNA was administered intracerebroventricularly at 48 h after MCAO. Recombinant rat TFF3 (rr-TFF3, 30 μg/Kg) or recombinant rat epidermal growth factor (rr-EGF, 100 μg/Kg) was administered intranasally at 1 h after recanalization, and EGFR inhibitor Gefitinib (75 mg/Kg) was administered intranasally at 30 min before recanalization. The evaluation of outcomes included neurobehavior, ELISA, western blot and immunofluorescence staining. TFF3 in hepatocytes and serum were upregulated in a similar time-dependent manner after MCAO. Compared to pMCAO, delayed recanalization increased brain TFF3 levels and attenuated brain damage with the reduction in neuronal apoptosis, infarct volume and neurological deficits. Partial hepatectomy reduced TFF3 levels in serum and ipsilateral brain hemisphere, and abolished the benefits of delayed recanalization on neuronal apoptosis and neurobehavioral deficits in rMCAO rats. Intranasal rrTFF3 treatment reversed the changes associated with partial hepatectomy. Delayed recanalization after MCAO increased the co-immunoprecipitation of TFF3 and LINGO2, as well as expressions of p-EGFR, p-Src and Bcl-2 in the brain. LINGO2 siRNA knockdown or EGFR inhibitor reversed the effects of delayed recanalization on apoptosis and brain expressions of LINGO2, p-EGFR, p-Src and Bcl-2 in rMCAO rats. EGFR activator abolished the deleterious effects of LINGO2 siRNA. In conclusion, our investigation demonstrated for the first time that delayed recanalization may enhance the entry of liver-derived TFF3 into ischemic brain upon restoring blood flow after MCAO, which attenuated neuronal apoptosis and neurological deficits at least in part via activating LINGO2/EGFR/Src pathway.Copyright © 2023. Published by Elsevier Inc.

基金：
This work was supported by the grants from the National Institutes of Health (Grant No. NS081740 and NS082184 to JHZ), Henan Province Science and Technology Research Project (Grant No. 222102310256 to DJL) and China International Medical Foundation (Grant No. Z-2016- 20-2101-06 to LFL).
语种：
外文
WOS：
PubmedID：
中科院(CAS)分区：
出版当年[2023]版：
大类 | 2 区 医学
小类 | 2 区 神经科学
最新[2025]版：
大类 | 2 区 医学
小类 | 2 区 神经科学
JCR分区：
出版当年[2022]版：
Q1 NEUROSCIENCES
最新[2023]版：
Q1 NEUROSCIENCES

影响因子： 最新[2023版] 最新五年平均 出版当年[2022版] 出版当年五年平均 出版前一年[2021版] 出版后一年[2023版]

第一作者：
第一作者单位： [1]Department of Pathology, Henan Provincial People’s Hospital (People’s Hospital of Zhengzhou University, People’s Hospital of Henan University), Zhengzhou 450003, [2]Department of Physiology and Pharmacology, Loma Linda University, Loma Linda, CA 92354, USA
共同第一作者：
通讯作者：
通讯机构： [1]Department of Pathology, Henan Provincial People’s Hospital (People’s Hospital of Zhengzhou University, People’s Hospital of Henan University), Zhengzhou 450003, [2]Department of Physiology and Pharmacology, Loma Linda University, Loma Linda, CA 92354, USA [4]Department of Neurosurgery, Loma Linda University, Loma Linda, CA 92354, USA [*1]Department of Pathology, Henan Provincial People’s Hospital, 7 Weiwu Road, Zhengzhou 450003, China. [*2]Department of Physiology and Pharmacology, Loma Linda University, 11041 Campus Street, Loma Linda, CA 92354, USA
推荐引用方式(GB/T 7714)：
Li Dujuan,Lian Lifei,Huang Lei,et al.Delayed recanalization reduced neuronal apoptosis and neurological deficits by enhancing liver-derived trefoil factor 3-mediated neuroprotection via LINGO2/EGFR/Src signaling pathway after middle cerebral artery occlusion in rats[J].EXPERIMENTAL NEUROLOGY.2024,371:doi:10.1016/j.expneurol.2023.114607.
APA：
Li Dujuan,Lian Lifei,Huang Lei,Gamdzyk Marcin,Huang Yi...&Zhang John H.(2024).Delayed recanalization reduced neuronal apoptosis and neurological deficits by enhancing liver-derived trefoil factor 3-mediated neuroprotection via LINGO2/EGFR/Src signaling pathway after middle cerebral artery occlusion in rats.EXPERIMENTAL NEUROLOGY,371,
MLA：
Li Dujuan,et al."Delayed recanalization reduced neuronal apoptosis and neurological deficits by enhancing liver-derived trefoil factor 3-mediated neuroprotection via LINGO2/EGFR/Src signaling pathway after middle cerebral artery occlusion in rats".EXPERIMENTAL NEUROLOGY 371.(2024)

相关文献

[1]Animal Models of Ischemic Stroke with Different Forms of Middle Cerebral Artery Occlusion [2]Control of occlusion of middle cerebral artery in perinatal and neonatal mice with magnetic force [3]Systematic evaluation during early-phase ischemia predicts outcomes in middle cerebral artery occlusion mice [4]The temporal evolution of diffusional kurtosis imaging in an experimental middle cerebral artery occlusion (MCAO) model [5]Glial gap-junction communication involvement in hippocampal damage and cognitive deficits following middle cerebral artery occlusion [6]Glial Gap Junctional Communication Involvement in Hippocampal Damage After Middle Cerebral Artery Occlusion [7]Disruption of NMDAR-CRMP-2 signaling protects against focal cerebral ischemic damage in the rat middle cerebral artery occlusion model [8]Cyclooxygenase-2 and Prostaglandin E2 are Associated with Middle Cerebral Artery Occlusion and Hemorrhage in Patients with Moyamoya Disease [9]Disruption of NMDAR-CRMP-2 signaling protects against focal cerebral ischemic damage in the rat middle cerebral artery occlusion model [10]Limb remote ischemic postconditioning is effective but also time-course-limited in protecting the brain from I/R injury

资源点击量：426 今日访问量：2 总访问量：410 更新日期：2025-04-01 建议使用谷歌、火狐浏览器 常见问题

版权所有：重庆聚合科技有限公司 渝ICP备12007440号-3 地址：重庆市两江新区泰山大道西段8号坤恩国际商务中心16层（401121）