Neuroprotective Effects of VEGF-A Nanofiber Membrane and FAAH Inhibitor URB597 Against Oxygen-Glucose Deprivation-Induced Ischemic Neuronal Injury.
Neuroprotective Effects of VEGF-A Nanofiber Membrane and FAAH Inhibitor URB597 Against Oxygen-Glucose Deprivation-Induced Ischemic Neuronal Injury.
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VEGF-A 纳米纤维膜和 FAAH 抑制剂 URB597 对缺氧和葡萄糖剥夺引起的缺血性神经元损伤的神经保护作用
DOI：
10.2147/ijn.s307335
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发表时间：
2021
影响因子：
8
通讯作者：
Hai J
中科院分区：
文献类型：
--
作者：
Wang DP;Jin KY;Zhao P;Lin Q;Kang K;Hai J
前言脑缺血是世界范围内一种常见的神经疾病，它会激活一连串的病理生理事件，包括氧气和葡萄糖水平的下降。尽管对其发病机制进行了大量的研究，但缺血性神经元损伤的治疗仍然是一个巨大的挑战。越来越多的证据表明，血管内皮生长因子修饰的纳米纤维材料和脂肪酸酰胺水解酶(FAAH)抑制剂URB597对减轻缺血性脑损伤有影响。我们的目的是进一步研究它们对原代海马神经元的影响，以及缺氧-葡萄糖剥夺(OGD)后的潜在机制。方法采用电纺丝的逐层自组装法制备了不同层次的血管内皮生长因子-A负载聚己内酯(PCL)纳米纤维膜。对制备的血管内皮生长因子-A纳滤膜的物化、生物学性能、形态、亲水性和控释性能进行了评价。此外，我们还研究了血管内皮生长因子和URB597对OGD诱导的线粒体氧化应激、炎症反应、神经元凋亡和内源性大麻素信号成分的影响。结果血管内皮细胞生长因子膜和URB597不仅能促进OGD后海马神经元的黏附和存活，而且具有抗氧化/抗炎和线粒体膜电位保护作用。VEGF-A核因子膜和URB597还通过激活CB1R信号通路抑制OGD诱导的细胞凋亡。这些结果表明，LBL自组装纳滤膜可以控制释放VEGF-A。[讨论]VEGF-A NF膜与URB597通过抑制线粒体氧化应激，激活CB1R/PI3K/AKT/BDNF信号通路，发挥正向协同神经保护作用，提示负载VEGF-A的NF膜和FAAH抑制剂URB597对缺血性脑血管疾病有一定的治疗价值。
Introduction Brain ischemia is a common neurological disorder worldwide that activates a cascade of pathophysiological events involving decreases in oxygen and glucose levels. Despite substantial efforts to explore its pathogenesis, the management of ischemic neuronal injury remains an enormous challenge. Accumulating evidence suggests that VEGF modified nanofiber (NF) materials and the fatty-acid amide hydrolase (FAAH) inhibitor URB597 exert an influence on alleviating ischemic brain damage. We aimed to further investigate their effects on primary hippocampal neurons, as well as the underlying mechanisms following oxygen–glucose deprivation (OGD). Methods Different layers of VEGF-A loaded polycaprolactone (PCL) nanofibrous membranes were first synthesized by using layer-by-layer (LBL) self-assembly of electrospinning methods. The physicochemical and biological properties of VEGF-A NF membranes, and their morphology, hydrophilicity, and controlled-release of VEGF-A were then estimated. Furthermore, the effects of VEGF-A NF and URB597 on OGD-induced mitochondrial oxidative stress, inflammatory responses, neuronal apoptosis, and endocannabinoid signaling components were assessed. Results The VEGF-A NF membrane and URB597 can not only promote hippocampal neuron adhesion and viability following OGD but also exhibited antioxidant/anti-inflammatory and mitochondrial membrane potential protection. The VEGF-A NF membrane and URB597 also inhibited OGD-induced cellular apoptosis through activating CB1R signaling. These results indicate that VEGF-A could be controlled-released by LBL self-assembled NF membranes. Discussion The VEGF-A NF membrane and URB597 displayed positive synergistic neuroprotective effects through the inhibition of mitochondrial oxidative stress and activation of CB1R/PI3K/AKT/BDNF signaling, suggesting that a VEGF-A loaded NF membrane and the FAAH inhibitor URB597 could be of therapeutic value in ischemic cerebrovascular diseases.