Aqueous carboyxfullerene analogue attenuated cerebral infarct and extracellular glutamate levels in anesthetized rat

We have examined the effects of an aqueous-soluble carboxyfullerene analogue on the cerebral ischemia-induced infarct volume, and on extracellular glutamate accumulation, in an anesthetized rat brain cortex. A C3-symmetric carboxylic acid derivative of C60 (C3-C60), which contains three malonic acid groups per molecule, was administered intraventricularly (5 μL of a 30-μM solution of C3-C60 over a period of 40 min). Cerebral ischemia was induced by the ligation of bilateral common carotid arteries (CCA) and the unilateral middle cerebral artery (MCA). The infarct volume was calculated by analysis of 2-mm coronal sections of brain slices that were stained using TTC. We analyzed the glutamate concentrations in the cortex by microdialysis perfusion and on-line HPLC analysis. Administering C3-C60 significantly decreases the infarct volume (infarct percentage relative to total volume: 8 ± 1.4%) when compared with the vehicle (22 ± 2.6%; p < 0.01), which was similar to that of the control (22 ± 1.2%). Additionally, administering C3-C60 significantly decreases ischemia-induced extracellular glutamate accumulation when compared with the vehicle. These results suggest that an aqueous-soluble analogue of carboxyfullerene can protect a cerebral ischemia-induced infarct. This protective effect may be related to the attention of the accumulation of extracellular excitatory amino acids such as glutamate. The detailed mechanisms underlying the neuroprotective effects of C3-C60 require further investigation.