Neuroprotective effects of urolithin a in a mouse model of intracerebral hemorrhage.

Intracerebral hemorrhage (ICH) accounts for 10-15 % of all stroke cases and is associated with high mortality and morbidity. Brain injury caused by ICH includes primary and secondary brain injury. Neuroinflammation and apoptosis play important roles in the pathological process of secondary brain injury after ICH. Urolithin A (UroA) is a metabolite derived from ellagic acid and has been confirmed to be anti-inflammatory, anti-oxidant and anti-apoptotic. The aim of this study was to investigate the effects of UroA on neuroinflammation and neuronal apoptosis in a mouse model of ICH induced by collagenase. Compared with ICH mice given vehicle, intraperitoneal injection of UroA (2.5 mg/kg) significantly reduced neurological impairment and brain water content 3 days after ICH. UroA reduced Evans Blue exudation and the loss of zonula occludens-1 and Occludin. Western blot showed that UroA significantly decreased the concentration of matrix metalloproteinases-9 (MMP-9). UroA treatment significantly attenuated the density of activated microglia and infiltrated neutrophils after 3 days of ICH. Finally, UroA inhibited cell death around the hematoma, attenuated ipsilateral brain injury, and improved neurological function in mice with ICH. UroA plays a neuroprotective role in ICH by inhibiting the expression of MMP-9 and reducing neuroinflammation, blood-brain barrier destruction, brain cell death and brain injury.