Abstracts

Rationale: Infantile spasms (IS) is a pediatric epilepsy syndrome with overall poor clinical outcome. We had previously developed the rat chronic model of symptomatic IS that recapitulates the chronic evolution of the human syndrome (multiple-hit model). In the multiple-hit model, rats receive intracerebral infusion of doxorubicin and lipopolysaccharide (LPS) at postnatal day 3 (P3) and systemic injection of p-chlorophenylalanine at P5 and experience spasms between P4-12. In this study, we examined whether intracortical injection of LPS suffices to generate spasms and if its effects are age-specific.Methods: Male Sprague-Dawley rats received right intracortical injections of LPS or saline at P3 or P14. Intermittent 2hr sessions of video-monitoring were performed twice daily from P4 to P19. Separate cohort of rats, injected with LPS or saline intracortically at P3 underwent video-EEG monitoring. Animal care and use conformed to institutional policy and guidelines.Results: In all rats that had received LPS at P3, flexion, extension or mixed spasms appeared between from P4 and P14. The frequency of spasms was the highest at P4, gradually decreased with age and was very low after P10. EEG showed correlated ictal changes consisting of high amplitude spikes wave complex and electrical attenuation (Figure). Rats injected with LPS at P14 did not show any spasms.Conclusions: Our study showed that intracortical focal injections of proinflammatory agents, like LPS, can trigger spasms in an age-specific manner. The availability of models of different underlying etiologies and/or pathologies may allow for the identification of common pathogenetic mechanisms and new therapies with broad efficacy on IS. This study was funded by NINDS/NICHD grant NS62947, NINDS grant 20253, a research grant from the Heffer Family Foundation.