Biochemical studies suggest that oxidation may be important in a number of brain pathologies. The few epidemiological studies are consistent with a protective effect of fruits and vegetables or antioxidants in a number of neurological pathologies, including brain ischemia, Parkinsons disease (PD), and familial amyotrophic lateral sclerosis (FALS), a degenerative disorder of motor neurons .
Ischemic episodes liberate iron, an important catalyst in oxygen radical forming reactions; iron chelators reduce neuron loss following this trauma. In individuals suffering from Parkinson's disease, oxidative DNA damaged is elevated within brain regions rich in dopaminergic neurons (E. Övervik, J. Sanchez-Ramos and B. Ames, unpublished). The most convincing evidence so far for a link between neurological disorders and oxygen radical formation is the strong association found between FALS and mutations in the Cu/Zn superoxide dismutase gene, suggesting that oxygen radicals might be responsible for the selective degeneration of motor neurons occurring in this fatal disease.
The protective role of superoxide dismutase against brain injury due to ischemia is supported by the finding that its overproduction is protective in a transgenic mouse model. Based on the similar protective effects against ischemia induced brain injury by inhibition of nitric oxide formation, and the recent evidence implicating these two radical species in cytotoxicity of neuronal cells, it would appear that peroxynitrite, a powerful oxidant formed from the combination of superoxide anion radical and nitric oxide, plays an important role in neuronal injury following ischemia and reperfusion.
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