Characterization of cortical spreading depression in adult well-nourished and malnourished rats submitted to the association of pilocarpine-induced epilepsy plus streptozotocin-induced hyperglycemia.

Spreading depression was characterized in adult rats rendered epileptic by pilocarpine (350 mg/kg, i.p.) and thereafter made hyperglycemic with (i.p.) 60 mg/kg streptozotocin. Groups treated with only one of the above drugs, as well as control groups treated with their vehicles (saline and citrate buffer, respectively) were also studied. The animals treated with pilocarpine or streptozotocin presented, as a common feature, a reduction in the spreading depression propagation rate. However, they differed by the fact that pilocarpine, in some cases, blocked spreading depression propagation, whereas streptozotocin did not block it at all. In early-malnourished animals, streptozotocin-effects, but not pilocarpine-effects on spreading depression were attenuated. The treatment with both drugs did not potentiate their individual reducing effects on spreading depression propagation, irrespective of the animals' early nutritional status. These results extend previous observations on rats treated with both drugs separately, confirming their impairing action on spreading depression propagation. They also indicate that early malnutrition is more effective in changing the streptozotocin effects on spreading depression, as compared to the pilocarpine-effects. Since such effects were observed at adulthood, they indicate that the early malnutrition-induced cortical changes responsible for the here-described effects are long-lasting.