Int J Nanomedicine. 2026 Jul 29;21:611089. doi: 10.2147/IJN.S611089. eCollection 2026.
ABSTRACT
INTRODUCTION: Cerebral ischemia-reperfusion injury (CIRI) involves complex pathogenesis with limited therapeutic options. This study investigated whether dexmedetomidine liposomes (Dex-lip) exert neuroprotective effects by modulating astrocytic aerobic glycolysis via calcium signaling.
METHODS: In vivo CIRI model mice received Dex-lip, with or without the aerobic glycolysis inhibitor 2-deoxy-D-glucose (2-DG). Neurological function, cortical calcium levels, aerobic glycolysis-related protein expression, lactate production, and hippocampal neuronal damage were assessed. In vitro, astrocytes were treated with the calcium channel blocker nifedipine to evaluate intracellular calcium, lactate levels, and glycolysis-related gene expression.
RESULTS: Dex-lip treatment reduced cortical calcium overload, upregulated aerobic glycolysis key proteins, increased lactate production, and attenuated hippocampal neuronal injury. These neuroprotective effects were abolished by 2-DG. In vitro, nifedipine lowered astrocytic calcium concentration, which paradoxically increased lactate production, elevated ECAR, and upregulated HK1, HK2, and PFK1 mRNA expression, confirming that calcium reduction promotes aerobic glycolysis.
CONCLUSION: Dex-lip ameliorates CIRI by reducing astrocytic calcium overload, enhancing aerobic glycolysis and lactate supply to neurons, thereby preventing apoptosis. This study provides a mechanistic basis and therapeutic strategy for CIRI.
PMID:42544301 | PMC:PMC13429122 | DOI:10.2147/IJN.S611089