NCAM mimetic peptide P2 synergizes with bone marrow mesenchymal stem cells in promoting functional recovery after stroke.
Xiao-Yan LanXue-Song LiangMing-Xuan CaoHua-Min QinCheng-Yan ChuJohannes BoltzeShen LiPublished in: Journal of cerebral blood flow and metabolism : official journal of the International Society of Cerebral Blood Flow and Metabolism (2024)
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.
Keyphrases
- signaling pathway
- pi k akt
- cell cycle arrest
- poor prognosis
- cell proliferation
- cerebral ischemia
- nuclear factor
- middle cerebral artery
- cell death
- oxidative stress
- cell adhesion
- binding protein
- diabetic rats
- atrial fibrillation
- high glucose
- stem cells
- endoplasmic reticulum stress
- heart failure
- toll like receptor
- drug induced
- acute myocardial infarction
- type diabetes
- long non coding rna
- internal carotid artery
- subarachnoid hemorrhage
- acute coronary syndrome
- spinal cord
- metabolic syndrome
- ischemia reperfusion injury
- spinal cord injury
- replacement therapy
- blood brain barrier