Respiratory and Arousal Mechanisms
Specific Aims and Tasks
Post-ictal respiratory depression has been proposed to contribute to SUDEP, and this may be particularly dangerous when combined with impaired arousal that commonly occurs after generalized tonic-clonic seizures. The combination of arousal and respiratory defects could explain why many SUDEPs occur with patients in bed in the prone position. This proposal has the following Specific Aims:
1 - Characterize interictal and ictal respiratory control and arousal in Dravet Syndrome patients and Dravet Syndrome mice.
2 - Identify the anatomical pathway from the forebrain that inhibits the respiratory control network during seizures.
3 - Determine which brainstem neurons are involved in peri-ictal inhibition of breathing and depressed arousal during seizures.
The proposed work is expected to help define the mechanisms underlying post-ictal hypoventilation and depression of arousal; identify biomarkers of SUDEP, and; discover preventive interventions for SUDEP.