Chronic treatment with ascorbic acid enhances cortical spreading depression in developing well-nourished and malnourished rats

Ascorbic acid (AA) is an antioxidant molecule that is highly concentrated in the brain and can exert both anticonvulsant and proconvulsant effects in distinct models of experimental seizures. Herein, we investigated whether chronic AA administration alters cortical excitability as indexed by the cortical spreading depression (CSD). Well-nourished (W) and malnourished (M) rats were treated, by gavage, with 60mg/kg/day of l-AA from postnatal days 7-28, and CSD propagation was analyzed at 30-40 days. Compared to the W groups, M rats presented higher (p<0.05) CSD amplitudes and velocities of propagation. In both nutritional conditions, AA-treatment significantly increased CSD amplitudes and propagation velocities (p<0.05), as compared to non-treated ('naïve'; Nv) and saline-treated (Sal) controls. The mean±standard deviation CSD velocities of propagation (in mm/min) for the Sal, AA and Nv groups were respectively 3.75±0.03, 4.26±0.08 and 3.81±0.04 for the W condition and 4.29±0.08, 4.51±0.04 and 4.30±0.04 for the M groups. The results demonstrate a CSD-facilitation by AA regardless of nutritional status. They also suggest that, at the dose of 60mg/kg/day chronically administered during brain development, AA may act as a prooxidant in brain, in view of the contrasting effect as compared with other antioxidants, which reduce CSD.