4-Methyllumifrone (4-MU) can improve learning and memory after cerebral ischemia/reperfusion injury in rats

Abstract Background Stroke is the sixth leading cause of death and lifelong disability for millions of people in the United States. Cerebral ischemia leads to oxidative stress, excitotoxicity, inflammation, apoptosis; additionally, impairments in memory and learning occur in the majority of subjects with ischemic stroke. The lack of definitive treatment has sparked extensive research into novel therapeutic strategies, including the use of 4-methylumbelliferone (4-MU), a coumarin derivative with potential neuroprotective properties. The present study examines the impact of 4-MU on reducing cerebral ischemia-reperfusion (I/R) injury and learning and memory impairments in male Wistar rats. Method The animals were exposed to middle cerebral artery occlusion (MCAO) and were treated with one dose of 4-MU (at a dosage of 25 mg/kg) dissolved in DMSO 0.9%. Automated shuttle box and Morris water maze (MWM) test were employed to evaluate learning and memory impairments. Western blot assay, TTC staining and Nissl staining were used to measure protein expression, infarct volume, and cell death, respectively. Results Results showed that treatment with 4-MU reduced infarct volume and improved learning and memory impairments by down-regulating HAS1 and HAS2. 4-MU has been shown to modulate the release of pro-inflammatory cytokines including TNF-α and IL-1β, as well as anti-inflammatory markers like IL-10 and also reduced oxidative stress markers in the brain. Conclusion Generally, the neuroprotective effects of 4-MU against cerebral I/R injury can be attributed to the down-regulation of HAS1 and HAS2.