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Abstract：
The neural cell adhesion molecule (NCAM) promotes neural development and regeneration. Whether NCAM mimetic peptides could synergize with bone marrow mesenchymal stem cells (BMSCs) in stroke treatment deserves investigation. We found that the NCAM mimetic peptide P2 promoted BMSC proliferation, migration, and neurotrophic factor expression, protected neurons from oxygen-glucose deprivation through ERK and PI3K/AKT activation and anti-apoptotic mechanisms in vitro. Following middle cerebral artery occlusion (MCAO) in rats, P2 alone or in combination with BMSCs inhibited neuronal apoptosis and induced the phosphorylation of ERK and AKT. P2 combined with BMSCs enhanced neurotrophic factor expression and BMSC proliferation in the ischemic boundary zone. Moreover, combined P2 and BMSC therapy induced translocation of nuclear factor erythroid 2-related factor, upregulated heme oxygenase-1 expression, reduced infarct volume, and increased functional recovery as compared to monotreatments. Treatment with LY294002 (PI3K inhibitor) and PD98059 (ERK inhibitor) decreased the neuroprotective effects of combined P2 and BMSC therapy in MCAO rats. Collectively, P2 is neuroprotective while P2 and BMSCs work synergistically to improve functional outcomes after ischemic stroke, which may be attributed to mechanisms involving enhanced BMSC proliferation and neurotrophic factor release, anti-apoptosis, and PI3K/AKT and ERK pathways activation.
摘要：
神经细胞粘附分子(NCAM)促进神经发育和再生。NCAM模拟肽是否能与骨髓间充质干细胞（BMSCs）在卒中治疗中协同作用值得研究。我们发现NCAM模拟肽P2促进BMSC增殖，迁移,和神经营养因子的表达，通过体外ERK和PI3K/AKT激活和抗凋亡机制保护神经元免受氧糖剥夺。大鼠大脑中动脉闭塞（MCAO）后，P2单独或与BMSCs联合抑制神经元凋亡并诱导ERK和AKT的磷酸化。P2联合BMSCs可增强缺血边界区神经营养因子的表达和BMSC的增殖。此外，P2和BMSC联合治疗可诱导核因子红系2相关因子易位，血红素加氧酶-1表达上调，梗死体积减少,与单调治疗相比，功能恢复增加。用LY294002(PI3K抑制剂)和PD98059(ERK抑制剂)治疗降低了P2和BMSC联合治疗在MCAO大鼠中的神经保护作用。总的来说，P2具有神经保护作用，而P2和BMSCs协同作用以改善缺血性卒中后的功能结果。这可能归因于涉及增强BMSC增殖和神经营养因子释放的机制，抗凋亡，PI3K/AKT和ERK通路激活。
