Intracerebral hemorrhage (ICH) resulting from the
rupture of the blood vessels in the brain is associated with significantly higher mortality and morbidity. Clinical studies focused on alleviating the primary injury,
hematoma formation and expansion, were largely ineffective, suggesting that secondary injury-induced
inflammation and the formation of reactive species also contribute to the overall injury process. In this study, we explored the effects of
cofilin knockdown in a mouse model of ICH. Animals given stereotaxic
injections of
cofilin siRNA, 72-h prior to induction of ICH by
collagenase injection within the area of
siRNA administration showed significantly decreased
cofilin expression levels and lower
hemorrhage volume and
edema, and the animals performed significantly better in neurobehavioral tasks i.e., rotarod, grip strength and
neurologic deficit scores.
Cofilin siRNA knocked-down mice had reduced ICH-induced DNA fragmentation, blood-brain barrier disruption and microglial activation, with a concomitant increase in astrocyte activation. Increased expression of pro-survival
proteins and decreased markers of oxidative stress were also observed in
cofilin siRNA-treated mice possibly due to the reduced levels of
cofilin. Our results suggest that
cofilin plays a major role in ICH-induced secondary injury, and could become a potential therapeutic target.