Novel Strategies for the Prevention of Post-Stroke Epilepsy and Sudden Unexpected Death in Epilepsy Patients

dc.contributor.advisorTruitt, William
dc.contributor.authorAdhikari, Yadav Prasad
dc.contributor.otherWitkin, Jeffrey M.
dc.contributor.otherGupta, Kunal
dc.contributor.otherBrutkiewicz, Randy
dc.contributor.otherJin, Xiaoming
dc.date.accessioned2022-11-08T16:01:08Z
dc.date.available2022-11-08T16:01:08Z
dc.date.issued2022-10
dc.degree.date2022en_US
dc.degree.discipline
dc.degree.grantorIndiana Universityen_US
dc.degree.levelPh.D.en_US
dc.descriptionIndiana University-Purdue University Indianapolis (IUPUI)en_US
dc.description.abstractStroke is the second leading cause of mortality worldwide, accounting for 5.5 million deaths annually. In addition to its high mortality rate, stroke is the most common cause of acquired epilepsy. Three to thirty percent of stroke survivors develop post-stroke epilepsy. Although currently available therapies such as thrombolytics and mechanical thrombectomy prevent immediate mortality by restoring blood flow after stroke, these treatments do not target the cellular and molecular mechanisms that lead to post-stroke epileptogenesis. With the increasing number of stroke survivors, there is an urgent need for therapies that prevent epilepsy development in this population. Here, we showed that homeostatic plasticity is involved in the development of hyperexcitability after stroke and can be targeted to prevent the development of post-stroke epilepsy. Using two-photon calcium imaging, we found that homeostatic regulation leads to cortical hyperexcitability after stroke. We also found that activity enhancement by optogenetic and pharmacological approaches can target homeostatic plasticity to prevent post-stroke epilepsy. This study demonstrates the high translational potential of activity enhancement as a novel strategy to prevent post-stroke epilepsy through regulating cortical homeostatic plasticity. Sudden premature death is a leading cause of death in patients with medically refractory epilepsy. This unanticipated death of a relatively healthy person with epilepsy in which no structural or toxicological cause of death can be identified after postmortem analysis is referred to as sudden unexpected death in epilepsy patients (SUDEP). Respiratory failure during seizures is an important underlying mechanism of SUDEP. Here, we showed that LPS-induced peripheral inflammation is protective against SUDEP. This protection is mediated at least in part via enhancing serotonergic function in the brain stem. To the best of our knowledge, this is the first study demonstrating the relationship between peripheral inflammation and SUDEP prevention.en_US
dc.description.embargo2024-11-01
dc.identifier.urihttps://hdl.handle.net/1805/30488
dc.identifier.urihttp://dx.doi.org/10.7912/C2/3057
dc.language.isoen_USen_US
dc.subjectactivity enhancementen_US
dc.subjectD-cycloserineen_US
dc.subjecthomeostatic plasticityen_US
dc.subjectinflammationen_US
dc.subjectpost-stroke epilepsyen_US
dc.subjectSUDEPen_US
dc.titleNovel Strategies for the Prevention of Post-Stroke Epilepsy and Sudden Unexpected Death in Epilepsy Patientsen_US
dc.typeThesis
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