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Updated: Sep 19, 2025
Intrastriatal Injection of Autologous Blood or Clostridial Collagenase as Murine Models of Intracerebral Hemorrhage
Published on: July 3, 2014
Neuroprotective effects of urolithin a in a mouse model of intracerebral hemorrhage
Yan Guo1, Xiangyu Zhang2, Jianzhong Deng3
1Department of Cerebrovascular Diseases, The Second Affiliated Hospital of Zhengzhou University, Zhengzhou, Henan, 450000, China; Academy of Medical Science, Zhengzhou University, Zhengzhou, Henan, 450000, China; Department of Neurology, Anyang District Hospital of Henan Province, Anyang, Henan, 455000, China.
Insights
Urolithin A (UroA) offers neuroprotection against intracerebral hemorrhage (ICH) by reducing brain inflammation and cell death. This study shows UroA improves neurological function in a mouse model of ICH.
Area of Science:
- Neuroscience
- Pharmacology
- Biochemistry
Background:
- Intracerebral hemorrhage (ICH) is a severe stroke type with high mortality.
- Secondary brain injury involves neuroinflammation and apoptosis.
- Urolithin A (UroA), a metabolite of ellagic acid, exhibits anti-inflammatory, antioxidant, and anti-apoptotic properties.
Purpose of the Study:
- To investigate the neuroprotective effects of UroA in a collagenase-induced mouse model of ICH.
- To assess UroA's impact on neuroinflammation and neuronal apoptosis post-ICH.
Main Methods:
- ICH was induced in mice using collagenase.
- Mice received intraperitoneal injections of UroA (2.5 mg/kg) or vehicle.
- Neurological impairment, brain water content, blood-brain barrier integrity (Evans Blue, ZO-1, Occludin), MMP-9 levels, microglial activation, neutrophil infiltration, and cell death were evaluated.
Main Results:
- UroA treatment significantly reduced neurological deficits and brain water content 3 days post-ICH.
- UroA mitigated blood-brain barrier disruption, indicated by reduced Evans Blue exudation and preserved tight junction proteins.
- UroA decreased MMP-9 levels, attenuated microglial activation and neutrophil infiltration, inhibited cell death, and lessened brain injury.
Conclusions:
- Urolithin A demonstrates significant neuroprotective effects in an ICH mouse model.
- UroA exerts its protective role by inhibiting MMP-9 expression, reducing neuroinflammation, preserving blood-brain barrier integrity, and preventing neuronal apoptosis.
- UroA holds potential as a therapeutic agent for managing intracerebral hemorrhage.
Abstract:
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.
