Curcumin-primed olfactory mucosa-derived mesenchymal stem cells mitigate cerebral ischemia/reperfusion injury-induced neuronal PANoptosis by modulating microglial polarization

• DOI: 10.1016/j.phymed.2024.155635
• Publication Date: 2024-04-20T06:00:08Z
• Authors: Ziwei Lan; Fengbo Tan; Jialin He; Jianyang Liu; Ming Lu; Zhiping Hu; Yi Zhuo; JunJiang Liu; Xiangqi Tang; Zheng Jiang; Aojie Lian; Yongheng Chen; Yan Huang
• Keywords: Olfactory mucosa

Cerebral ischemia-reperfusion (I/R) injury often leads to neuronal death through persistent neuroinflammatory responses. Recent research has unveiled a unique inflammatory programmed cell mode known as PANoptosis. However, direct evidence for PANoptosis in ischemic stroke-induced not been established. Although it is widely thought that modulating the balance of microglial phenotypic polarization cerebral I/R could mitigate neuroinflammation-mediated death, remains unknown whether influences PANoptotic triggered by I/R. Our prior study demonstrated curcumin (CUR) preconditioning boost neuroprotective properties olfactory mucosa-derived mesenchymal stem cells (OM-MSCs) intracerebral hemorrhage. Yet, potential capacity curcumin-pretreated OM-MSCs (CUR-OM-MSCs) on reducing during uncertain. To mimic injury, We established vivo models reversible middle artery occlusion (MCAO) C57BL/6 mice and vitro oxygen-glucose deprivation/reoxygenation (OGD/R) HT22 neurons BV2 microglia. findings indicated caused microglia adopt an M1 (pro-inflammatory) phenotype both vitro. Curcumin pretreatment enhanced proliferation anti-inflammatory OM-MSCs. The CUR-OM-MSCs group experienced more pronounced reduction better recovery neurological function than group. Bioinformatic analysis revealed microRNA-423-5p (miRNA-423-5p) expression was obviously upregulated compared treatment induced switch M2 (anti-inflammatory) releasing miRNA-423-5p, which targeted nucleotide-binding oligomerization domain 2 (NOD2), upstream regulator NF-kappaB (NF-κB) Mitogen-Activated Protein Kinase (MAPK) signaling pathways, attenuate resulting from This results provide first demonstration existence conditions. ameliorating effect neuroinflammation mediated via upregulating abundance miRNA-423-5p. intervention effectively alleviates combination with holds promise potentially efficacious stroke future.