AAV-mediated VEGFA overexpression promotes angiogenesis and recovery of locomotor function following spinal cord injury via PI3K/Akt signaling

被引：8

作者：

Miao, Xin ^{[1
,2
]}

Lin, Junqing ^{[1
,2
]}

Li, Ang ^{[1
,2
]}

Gao, Tao ^{[1
,2
]}

Liu, Tiexin ^{[1
,2
]}

Shen, Junjie ^{[1
,2
]}

Sun, Yi ^{[1
,2
]}

Wei, Jiabao ^{[1
,2
]}

Bao, Bingbo ^{[1
,2
]}

Zheng, Xianyou ^{[1
,2
]}

机构：

[1] Shanghai Jiao Tong Univ, Shanghai Peoples Hosp 6, Dept Orthopaed Surg, Sch Med, Shanghai, Peoples R China

[2] Natl Ctr Orthopaed, Shanghai, Peoples R China

来源：

EXPERIMENTAL NEUROLOGY | 2024年 / 375卷

基金：

中国国家自然科学基金;

关键词：

Spinal cord injury; Adeno-associated virus; VEGFA; Angiogenesis; PI3K/Akt signaling pathway; ENDOTHELIAL GROWTH-FACTOR; BARRIER PERMEABILITY; VASCULAR DISRUPTION; CONTUSION; REGENERATION;

D O I：

10.1016/j.expneurol.2024.114739

中图分类号：

Q189 [神经科学];

学科分类号：

071006 ;

摘要：

Spinal cord injury (SCI) is a disorder of the central nervous system resulting from various factors such as trauma, inflammation, tumors, and other etiologies. This condition leads to impairment in motor, sensory, and autonomic functions below the level of injury. Limitations of current therapeutic approaches prompt an investigation into therapeutic angiogenesis through persistent local expression of proangiogenic factors. Here, we investigated whether overexpression of adeno-associated virus (AAV)-mediated vascular endothelial growth factor A (VEGFA) in mouse SCI promoted locomotor function recovery, and whether the phosphoinositide 3-kinase (PI3K)/protein kinase B (Akt) pathway was mechanistically involved. Three weeks before SCI, AAV-VEGFA was injected at the T10 level to induce VEGFA overexpression. Neurofunctional, histological, and biochemical assessments were done to determine tissue damage and/or recovery of neuromuscular and behavioral impairments. Daily injections of the PI3K/Akt pathway inhibitor LY294002 were made to assess a possible mechanism. AAV-VEGFA overexpression dramatically improved locomotor function and ameliorated pathological injury caused by SCI. Improved motor-evoked potentials in hindlimbs and more spinal CD31-positive microvessels were observed in AAV-VEGFA-overexpressing mice. LY294002 reduced PI3K and Akt phosphorylation levels and attenuated AAVVEGFA-related improvements. In conclusion, sustained local AAV-mediated VEGFA overexpression in spinal cord can significantly promote angiogenesis and ameliorate locomotor impairment after SCI in a contusion mouse model through activation of the PI3K/Akt signaling pathway.

引用

页数：11

共 71 条

[61] The role of PI3K/Akt signalling pathway in spinal cord injury [J].