Abstracts

Rationale: Cerebral malaria (CM) annually affects more than 3 million children typically under the age of 5. CM carries a high mortality rate even when treated. Epilepsy occurs in 10-16 % of children who survive CM. We have developed the first murine model of post-cerebral malaria epilepsy (PoME). We report here on histological analysis from the cohort of animals studied for the development of epilepsy, and correlate the neuropathophysiology with electrographic semiology Methods: Cohorts of mice of 3 different strain Swiss Webster (SW), CBA, and C57BL/6 were inoculated with Plasmodium berghei ANKA (PbANKA) and Plasmodium berghei NK65 (PbNK65) infected erythrocytes. After developing severe CM, they were treated with Artesunate and cured of the infection. They were then implanted with electrodes and chronically monitored with video/EEG for development of seizures. Littermate controls were inoculated with uninfected erythrocytes and treated identically to infected animals. EEG was analyzed to identify seizures, which were then scored for electrographic origin and evolution. Following chronic recording, their brains were fixed, sectioned and stained with GFAP and NeuN for astrocytes and neurons. Sections were analyzed using stereological technique to quantify hippocampal volume and region-specific cell densities. These quantities along with peak infectious phase Parasitemia were then correlated with animal specific seizure semiology. Results: Infected animals showed a range of morphological changes that included significantly expanded ventricles, damaged cortices, and asymmetrically affected hippocampi. Conclusions: There is an urgent need of effective adjunct therapy during and following CM to mitigate the effects of the insult and prevent chronic irreversible brain damage and associated deficits. This murine model of PoME will provide a useful platform to test mechanistic approaches for such interventions. Funding: Multidisciplinary grant from Citizen's United for Research in Epilepsy (CURE)