Inhibition of middle cerebral artery occlusion-induced focal cerebral ischemia 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-a and IL-1 p 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.