Semester Award Granted

Summer 2025

Submission Date

August 2025

Document Type

Thesis

Degree Name

Master of Science (MS)

Thesis/Dissertation Advisor [Chair]

Ceylan Isgor

Abstract

Interleukin-1 β (IL- 1β) is a proinflammatory cytokine with proconvulsive properties that is elevated in epilepsy. The hippocampal dentate gyrus (DG) buffers hyperexcitability, and deficits in granule neuron gating contribute to epileptogenesis. Excess brain derived neurotrophic factor (BDNF) may drive hyperexcitable circuit assembly, promoting a seizure-producing breakdown of the gating function. We use a transgenic mouse model of forebrain BDNF (TgBDNF) overexpression that exhibit spontaneous generalized tonic/ clonic seizures (GTCSs) at ~3 months, which progress as evidenced by prolonged periods of post-generalized EEG suppression (PGES). This is accompanied by hippocampal hypertrophy and brainstem cell loss. A strain globally lacking IL-1 type I receptor (IL-1R1) is bred with TgBDNF mice to assess epilepsy using subdural cortical EEG/video. It is hypothesized that removal of IL-1R1 will prevent epileptogenesis and/or mitigate seizure associated death risk/neuronal injury.

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