The Targeted Research Initiative for Morbidity and Mortality in Epilepsy supports research that generates initial data leading to more extensive projects that will generate knowledge that will ultimately improve the lives of persons with epilepsy. This initiative recognizes the need for research and new insights into these scientific areas.
The broad focus of the morbidity portion of this program includes: identification of somatic comorbidities in epilepsy that occur more than expected among controls, including but not limited to diabetes, gastrointestinal bleeding, chronic lung disease, congenital cardiac abnormalities, heart failure, and pneumonia; and associations between somatic comorbidities in epilepsy and epilepsy outcomes, including quality of life in epilepsy, seizure remission, stigma and other outcomes.
The mortality portion of the program is focused upon potentially preventable causes of death in epilepsy, such as accidents, suicide and SUDEP. Applicants are encouraged to examine risk factors for these causes of death in epilepsy; as well as interventions to decrease the presence of risk factors for these causes of death where risk factors have been identified.
SPRING 2015 AWARDS
Gordon Buchanan, M.D., Ph.D.
The University of Iowa, Iowa City, IA
Norepinephrine & serotonin in seizure-induced respiratory arrest and death
SUDEP is the leading cause of death in patients with refractory epilepsy. Seizure-induced respiratory arrest (SIRA) is frequently implicated in SUDEP. The neurotransmitter serotonin has been implicated in SUDEP, especially in the respiratory consequences of seizures. Other neurotransmitters, such as norepinephrine (NE), can also be released during seizures and influence breathing. Preliminary data suggest that fluoxetine, a selective serotonin reuptake inhibitor that also has activity at NE receptors is able to prevent SIRA and death in mice that do not have serotonin neurons in the brain. This suggests a role for NE receptor activation. Here we propose to further characterize a role of NE in SIRA and death in a mouse seizure model. Previous work shows that many mice that experience such seizures suffer SIRA and die. It is also known that pharmacological up-regulation of the serotonin system prior to the seizure can prevent SIRA and death. We propose to use a similar approach to examine a role for NE in SIRA and death. Gaining a better understanding of ways to support breathing and prevent death following seizures in animal models that are relevant to SUDEP may reveal preventive strategies to employ in patients with epilepsy.