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作者

Jing Wang, Yichen Cai, Jingyi Sun, Hua Feng, Xiaoyu Zhu, Qian Chen, Feng Gao, Qingbin Ni, Leilei Mao, Mingfeng Yang, Baoliang Sun

作者单位

com. ⁸ Medical College of Qingdao University, Qingdao 266021, Shandong, China School of Basic Medical Sciences of Shandong First Medical University, Shandong Academy of Medical Sciences, Taian 271000, Shandong, China. Electronic address: leilei-0318@16 School of Basic Medical Sciences of Shandong First Medical University, Shandong Academy of Medical Sciences, Taian 271000, Shandong, China. Electronic address: blsun88@16 com. ⁷ Institute for Neurological Research, The Second Affiliated Hospital, China School of Basic Medical Sciences of Shandong First Medical University, Shandong Academy of Medical Sciences, Taian 271000, Shandong, China. Electronic address: mfyang@16 School of Basic Medical Sciences of Shandong First Medical University, Shandong Academy of Medical Sciences, Taian 271000, Shandong, China. ² Institute for Neurological Research, The Second Affiliated Hospital, China Institute for Neurological Research, The Second Affiliated Hospital, China School of Basic Medical Sciences of Shandong First Medical University, Shandong Academy of Medical Sciences, Taian 271000, Shandong, China. ³ Department of Spinal Surgery, Shandong Provincial Hospital Affiliated to Shandong First Medical University, Jinan 250021, Shandong, China. ⁴ Department of Otolaryngology, Affiliated Hospital of Shandong University of Traditional Chinese Medicine, Jinan 250011, Shandong, China. ⁵ Postdoctoral Workstation, Taian Central Hospital, Taian 271000, Shandong, China. ⁶ Institute for Neurological Research, The Second Affiliated Hospital, China com. Affiliations ¹ Medical College of Qingdao University, Qingdao 266021, Shandong, China

刊名

Experimental neurology

年份

2022

页码

114236

ISSN

1090-2430

关键词

BDNF Stroke Synaptic plasticity TrkB

摘要

Stroke causes long-term disability in survivors. BDNF/TrkB plays an important role in synaptic plasticity and synaptic transmission in the central nervous system , promoting neurological recovery. In this study, we performed non-invasive treatment methods focused on intramuscular injection into stroke-injured forelimb muscles, or intranasal administration using adeno-associated virus vectors carrying genes encoding BDNF or TrkB. In a permanent rat middle cerebral artery occlusion model, we ass...更多

Stroke causes long-term disability in survivors. BDNF/TrkB plays an important role in synaptic plasticity and synaptic transmission in the central nervous system , promoting neurological recovery. In this study, we performed non-invasive treatment methods focused on intramuscular injection into stroke-injured forelimb muscles, or intranasal administration using adeno-associated virus vectors carrying genes encoding BDNF or TrkB. In a permanent rat middle cerebral artery occlusion model, we assessed the effects of combination therapy with AAV-BDNF and AAV-TrkB on motor functional recovery and synaptic plasticity of the corticospinal connections. Our results showed that BDNF or TrkB gene transduced in the spinal anterior horn neurons and cerebral cortical neurons. Compared to AAV vector treatment alone, behavioral and electrophysiological results showed that the combination therapy significantly improved upper limb motor functional recovery and neurotransmission efficiency after stroke. BDA tracing, immunofluorescence staining, qRT-PCR, and transmission electron microscopy of synaptic ultrastructure results revealed that the combination therapy not only potently increased the expression of Synapsin I, PSD-95, and GAP-43, but also promoted the axonal remodeling and restoration of abnormal synaptic structures. These findings provide a new strategy for enhancing neural plasticity and a potential means to treat stroke clinically.收起

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