Poloxamer 188 alleviates cerebral ischemia-reperfusion injury in mice by reducing mitochondrial and lysosomal membrane damage.

Objectives: To explore the beneficial effects and mechanisms of Poloxamer 188 (P188) in mitigating cerebral ischemia-reperfusion (I/R) injury in mice.

Methods: This study was conducted from 2020 to 2022. Neurological function, brain water content, and infarct size were assessed in mice 24 h after I/R injury. Iridium-labeled Poloxamer 188 (Ir-P188) was characterized using ¹H-NMR, UV-Vis spectroscopy, and fluorescence emission analysis. Immunofluorescence was used to evaluate intracellular distribution of Ir-P188 in OGD/R-induced HT22 cells in vitro and ischemic mice in vivo. 24 h after reperfusion, the levels of ROS and inflammation in ischemic brain were measured, along with the protein levels of mitochondrial, lysosomal, and cytoplasmic fractions. Additionally, the protective effects of p188 and Ginkgolide B, both as single agents and in combination, against I/R were compared.

Results: P188 intravenous administration could significantly reduce the infarct brain areas, improved neurological deficit, and decreased brain water content in mice after I/R injury. The accumulation of Ir-P188 was observed in OGD/R-induced HT22 cells and ischemic brain in mice. P188 suppressed ROS, inflammatory factors (NF-kB, IL-6, TNF-a), and inhibiting mitochondrial cytochrome C release and lysosomal protease translocation to the cytoplasm.

Conclusion: P188 can penetrate intracellular compartments and effectively protect mice against I/R injury. The underlying mechanism may involve inhibiting ROS generation, mitigating inflammatory responses, and alleviating mitochondrial dysfunction and lysosomal damage.