CNS Neurosci Ther. 2026 Aug;32(8):e71081. doi: 10.1002/cns.71081.
ABSTRACT
BACKGROUND: Ischemic stroke (IS), the main stroke type, causes neuronal injury via hypoperfusion and hypoxia, imposes heavy health burdens, and is characterized by neurological deficits driven by oxidative stress and inflammation.
METHODS: A rat model of IS was established via middle cerebral artery occlusion (MCAO). Sensorimotor and cognitive dysfunctions post-IS were assessed using neurological function scoring, the rotarod test, the adhesive removal test, the foot-fault test, and the Morris water maze (MWM) test. Brain injury was evaluated by TTC staining, immunofluorescence staining, and Western blotting. For mechanistic exploration, RNA transcriptome sequencing analysis, immunofluorescence staining, and ELISA were employed to determine UA's effects on oxidative stress and neuroinflammation following IS.
RESULTS: UA treatment was confirmed to exert neuroprotective effects against ischemic stroke, as it can inhibit neuronal injury and improve sensorimotor and cognitive functions in rats. Mechanistically, UA upregulates the expression of Nrf2/HO-1, thereby enhancing antioxidant capacity characterized by increased levels of antioxidant enzymes (SOD, GSH, GSH-Px) and decreased level of the lipid peroxidation marker MDA. Additionally, UA suppresses neuroinflammation, which is manifested by reduced levels of pro-inflammatory cytokines (TNF-α, IL-1β, IL-6) and elevated level of the anti-inflammatory cytokine IL-10. RNA transcriptome sequencing analysis further revealed that these neuroprotective effects of UA may be associated with inhibition of pathological NF-κB activation.
CONCLUSION: Urolithin A may exert neuroprotective effects against ischemic stroke by inhibiting oxidative stress and neuroinflammation. Collectively, this study provides theoretical support for the clinical translation of UA as a poststroke neuroprotective agent.
PMID:42590804 | DOI:10.1002/cns.71081