Inhibition of middle cerebral artery occlusion-induced focal cerebral ischernia by carboxyfullerene

The neuroprotective effects of a water-soluble trimalonic acid derivative of fullerene, carboxyfullerene, were evaluated in mice subjected to permanent middle cerebral artery occlusion (MCAO). The ischemic disruption of the blood-brain barrier (BBB) was shown by its permeability to the peripheral M4 tracer and the damage of endothelial cells. Cytokines TNF-alpha and IL-1beta were expressed on arterioles. Relatively to vehicle-treated controls, mice treated with carboxyfullerene (40 mg/kg) at the time of ischemia showed a 75% reduction in brain infarction. This inhibition was dose- and time-dependent. There was still significant inhibition 6 h post-occlusion. With anti-carboxyfullerene antibody immunohistochemical staining, carboxyfullerene was detectable on the neurons and ventricle in the ipsilateral hemisphere of the carboxyfullerene-treated mice. This suggests that carboxyfullerene can be a potential therapeutic agent for MCAO-induced focal cerebral ischemia treatment.