Abstracts

Rationale: We have previously reported in the tetrodotoxin (TTX) model of infantile spasms a depression of background neocortical EEG activity in and around the TTX infusion site which persisted for more than 3-4 weeks after the cessation of TTX infusion. Since this could contribute to the etiology of spasms in these animals, we have examined structural changes and mitochondrial cytochrome oxidase (COx) activity in the neocortex of these animals.Methods: Infusion of TTX was started at postnatal day (PND) 11 – 12 and continued for 4 weeks. During or immediately after the infusion period, electrodes were implanted to monitor EEG activity. At predetermined intervals, animals were rapidly perfused with buffer followed by buffered formalin to lightly fix the brain. Brains were removed and cryoprotected in 30% sucrose before being frozen and sectioned at 30 µm thickness. Sections were then analyzed using a standard COx method.Results: As expected from previous results, EEG activity was depressed up to at least 1.5 mm from the infusion site and persisted well beyond the period of TTX infusion. Results from 3 TTX infused animals studied on PND 50, 55 and 78 showed a decrease in cortical thickness, reflecting an atrophy of cortical laminae. These animals also showed a decrease in COx activity. Over time (PND 50 to 78), the suppressed activity of COx and the atrophy persisted. No obvious structural or COx alterations have been observed in vehicle infused (PND 70) or naïve control rats (PND 78).Conclusions: Results suggest that infusion of TTX leads to a local atrophy of neocortex along with a persistent decrease in metabolic (COx ) activity. This acquired neuropathology could contribute to genesis of spasms in this animal model.