Effect of aging on cortical spreading depression

The effects of aging on spreading depression (SD) were investigated in the Mongolian gerbil (G; age range 1.5 to 58 months; N = 35) and in the albino rat (R; 2.5 to 24 months; N = 100). Two strains of rats were studied: Wistar (W; N = 35) and Sprague-Dawley (SDAW; N = 65). SDAW rats were divided into two groups: one group was fed a commercial lab chow diet (CD) containing 22 per cent protein (N = 47), and the other was fed a 22 per cent casein diet (CAS; N = 18). SD was elicited on the frontal cortical surface by 1-min application of 2 per cent KCl and its appearance was recorded (ECoG and DC potential) at two points in the parieto-occipital area of the same hemisphere. SD propagation velocity was measured on the basis of the time spent for an SD "wave" to cross the distance between the two recording points. Within the age range studied, older animals displayed significantly lower SD velocities than the younger ones, independent of the species, strain or diet (velocity ranges, in mm/min: G, 2.22-5.99; W, 2.47-4.12; SDAW-CD, 2.32-4.42 and SDAW-CAS, 2.65-4.14). The correlation coefficients between age and SD velocity were: G, -0.78; W, -0.45; SDAW-CD, -0.68 and SDAW-CAS, -0.72 (P<0.05 in all cases). As a rule, at each time point the gerbils presented higher SD velocities than the rats of the same age. In another set of experiments, in order to test the role of free radicals in SD, 7 gerbils (14-51 months old) and 13 W rats (3-24 months old) were fed a 22 per cent casein diet free of the antioxidant vitamins C and E for 4-6 weeks before the experiments. No correlation was found between age and SD propagation in these animals fed a diet free of vitamins C and E, although gerbils displayed higher SD velocities than age-matched rats (velocities: G, 3.70-5.34; R, 3.25-4.44 mm/min; correlation coefficients: G, -0.39; W, -0.29; P>0.05). These data indicate that gerbils have higher SD susceptibility than rats of the same age, and that this susceptibility decreases with aging in both species. The lack of correlation between age and SD velocity in the animals fed a diet free of antioxidant vitamins suggests a possible role of free radicals in cortical SD, in accordance with evidence from other laboratories obtained in the isolated retina.

Effect of dietary lithium on cortical spreading depression

The influence of lithium administration on cortical spreading depression (SD) was investigated in rats whelped by dams fed a diet containing lithium (1.5 g/kg) during the gestation or the lactation periods. Velocity of SD propagation was measured when the rats became adults and was similar to that of rats raised on a normal diet. A third group of adult rats received lithium during the three weeks preceding SD recordings and presented a significant reduction in SD velocity as compared to control rats. These data suggest that in adult rat a brief treatment with lithium impairs SD propagation, whreas much earlier treatment does not

Apomorphine does not mimic the effects of rem-sleep deprivation on cortical spreading depression

The propagation of cortical spreading depression (SD) and the incidence of "spontaneous" SD were enhanced in rats after rapid-eye-movement sleep deprivation (REMD) as compared to control animals. Pseudo-deprived rats were similar to controls, suggesting that the facilitatory effect on SD is due to REMD rather than to the stress accompanying deprivation. In control rats, apomorphine (0.5 to 8 mg/kg) failed to reproduce the effects of REMD and also failed to enhance the REMD effects in deprived rats, suggesting that the dopaminergic system does not play an important role in propagation of cortical SD