Indiana University-Purdue University Indianapolis (IUPUI) / Stroke 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. / 2024-11-01
| Identifer | oai:union.ndltd.org:IUPUI/oai:scholarworks.iupui.edu:1805/30488 |
| Date | 10 1900 |
| Creators | Adhikari, Yadav Prasad |
| Contributors | Truitt, William, Witkin, Jeffrey M., Gupta, Kunal, Brutkiewicz, Randy, Jin, Xiaoming |
| Source Sets | Indiana University-Purdue University Indianapolis |
| Language | en_US |
| Detected Language | English |
| Type | Dissertation |
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