Dietary Antioxidant Deficiency Facilitates Cortical Spreading Depression Induced by Photoactivated Riboflavin

It is known that the photoactivation of riboflavin produces superoxide radicals. We investigated the ability of this process to elicit spreading depression (SD) in the cerebral cortex of adult rats receiving either a normal diet (control group; n = 9) or fed a diet free from vitamins C and E during 4-6 weeks prior to the experiment (deficient group; n = 15). SD was initially elicited, at 20 min intervals, by 2% KC1 topically applied for 1 min to a point (2-3 mm in diameter) on the dura mater at the frontal cortex and SD propagation was monitored by both EEG and DC-recordings at two points of the parietal region. After a 1-2 h "baseline" recording of KCl-elicited SD, tests were performed with 1.0 mM riboflavin applied to the same frontal region and illuminated by a white light bulb (40 W, 10-15 cm from the cortical surface, for 1-3 min). In the control group, 37 applications of riboflavin + light were performed (average: 4.1 applications per rat; range: 3-7) and 11 of these applications (29.7%) elicited SD in 7 out of the 9 rats. In the deficient group, the effectiveness of photoactivated riboflavin to elicit SD increased significantly to 62.8% (44 out of 70 applications; 15 out of 15 rats; average: 4.7 applications per rat; range: 3-6; P < 0.05). Elicitation of SD was not obtained, either by illumination of an equivalent volume of Ringer solution applied to the same region, or by riboflavin applied without illumination. The results demonstrate that photoactivated riboflavin is capable of eliciting SD in the rat cerebral cortex, and that dietary deficiency of the antioxidant vitamins C and E can enhance brain susceptibility to this process.