Arundic Acid (ONO-2506) Attenuates Neuroinflammation and Prevents Motor Impairment in Rats with Intracerebral Hemorrhage

Intracerebral hemorrhage (ICH) is a severe stroke subtype caused by the rupture of blood vessels within the brain. Increased levels of S100B protein may contribute to neuroinflammation after ICH through activation of astrocytes and resident microglia, with the consequent production of proinflammatory cytokines and reactive oxygen species (ROS). Inhibition of astrocytic synthesis of S100B by arundic acid (AA) has shown beneficial effects in experimental central nervous system disorders. In present study, we administered AA in a collagenase-induced ICH rodent model in order to evaluate its effects on neurological deficits, S100B levels, astrocytic activation, inflammatory, and oxidative parameters. Rats underwent stereotactic surgery for injection of collagenase in the left striatum and AA (2 mu g/mu l; weight x 0.005) or vehicle in the left lateral ventricle. Neurological deficits were evaluated by the Ladder rung walking and Grip strength tests. Striatal S100B, astrogliosis, and microglial activation were assessed by immunofluorescence analysis. Striatal levels of interleukin 1 beta (IL-1 beta) and tumor necrosis factor alpha (TNF-alpha) were measured by ELISA, and the ROS production was analyzed by dichlorofluorescein (DCF) oxidation. AA treatment prevented motor dysfunction, reduced S100B levels, astrogliosis, and microglial activation in the damaged striatum, thus decreasing the release of proinflammatory cytokines IL-1 beta and TNF-alpha, as well as ROS production. Taken together, present results suggest that AA could be a pharmacological tool to prevent the harmful effects of increased S100B, attenuating neuroinflammation and secondary brain damage after ICH.

Automated summary

In this study, arundic acid (AA) was administered in a collagenase-induced intracerebral hemorrhage (ICH) rodent model, and it was found that AA could prevent motor dysfunction, reduce S100B levels, and decrease astrogliosis and microglial activation, which in turn led to a decrease in the production of proinflammatory cytokines and reactive oxygen species (ROS).