期刊
EXPERIMENTAL NEUROLOGY
卷 299, 期 -, 页码 97-108出版社
ACADEMIC PRESS INC ELSEVIER SCIENCE
DOI: 10.1016/j.expneurol.2017.10.014
关键词
Apolipoprotein E; Spinal cord-blood-barrier; Neuroprotection; Treatment; Spinal cord injury
资金
- National Institutes of Health [R01 NS099635]
- Staman Ogilvie Fund for Spinal Cord Injury Recovery
- Craig H. Neilsen Foundation [385446]
- Mission Connect-a project of The TIRR Foundation
- NATIONAL INSTITUTE OF NEUROLOGICAL DISORDERS AND STROKE [R01NS099635] Funding Source: NIH RePORTER
Apolipoprotein E (apoE), a plasma lipoprotein well known for its important role in lipid and cholesterol metabolism, has also been implicated in many neurological diseases. In this study, we examined the effect of apoE on the pathophysiology of traumatic spinal cord injury (SCI). ApoE-deficient mutant (apoE(-/-)) and wild-type mice received a T9 moderate contusion SCI and were evaluated using histological and behavioral analyses after injury. At 3 days after injury, the permeability of spinal cord-blood-barrier, measured by extravasation of Evans blue dye, was significantly increased in apoE(-/-) mice compared to wild type. The inflammation and spared white matter was also significantly increased and decreased, respectively, in apoE(-/-) mice compared to the wild type ones. The apoptosis of both neurons and oligodendrocytes was also significantly increased in apoE(-/-) mice. At 42 days after injury, the inflammation was still robust in the injured spinal cord in apoE(-/-) but not wild type mice. CD45 + leukocytes from peripheral blood persisted in the injured spinal cord of apoE(-/-) mice. The spared white matter was significantly decreased in apoE(-/-) mice compared to wild type ones. Locomotor function was significantly decreased in apoE(-/-) mice compared to wild type ones from week 1 to week 8 after contusion. Treatment of exogenous apoE mimetic peptides partially restored the permeability of spinal cord blood-barrier in apoE(-/-) mice after SCI. Importantly, the exogenous apoE peptides decreased inflammation, increased spared white matter and promoted locomotor recovery in apoE(-/-) mice after SCI. Our results indicate that endogenous apoE plays important roles in maintaining the spinal cord-blood-barrier and decreasing inflammation and spinal cord tissue loss after SCI, suggesting its important neuroprotective function after SCI. Our results further suggest that exogenous apoE mimetic peptides could be a novel and promising neuroprotective reagent for SCI.
作者
我是这篇论文的作者
点击您的名字以认领此论文并将其添加到您的个人资料中。
推荐
暂无数据