# A Biofidelic Model of PTE (Project 1)

> **NIH NIH P01** · MASSACHUSETTS GENERAL HOSPITAL · 2024 · $251,558

## Abstract

Project 1 Summary
Post-traumatic epilepsy (PTE) affects 15-40% of those with traumatic brain injury (TBI) causing
significant morbidity even after initial recovery from the TBI. Major limitations in understanding the
pathophysiology of PTE are a lack of biofidelic modeling of PTE in the gyrencephalic brain and
biomarkers that identify or predict PTE. Our long-term goal is to understand the pathophysiology the
leads to PTE in order to develop therapies that halt or inhibit the progression of pathogenesis that leads
to post-traumatic epilepsy. The overall objective is to identify biomarkers of PTE in a gyrencephalic
brain and the ionic basis of PTE. Our central hypotheses are that long-term ionic changes alters
GABAergic signaling leading to PTE and biomarkers of PTE can be identified with machine learning
boosting algorithms. The rationale is that a toolkit of automated methods of quantifying biomarkers in a
biofidelic model of PTE along with insight into the ionic changes that mediate GABAergic signaling will
allow identification of new therapeutic targets and allow efficient testing of those targets to prevent the
development of PTE in patients with TBI.
We will test our central hypotheses with two Specific Aims: Aim 1: We will train previously established
algorithms to identify the best mode, or combination of modes, to identify seizure candidates in these
models of PTE and maybe to even predict PTE. We hypothesize that we can use existing algorithms to
rapidly analyze behavior and ECoG, identify seizure correlates, and together with peripheral serum
biomarkers, use existing boosting algorithms to predict which subjects will develop PTE. Aim 2: We will
determine if chronic changes in the ionic basis of GABAergic signaling and in the neocortical network
activity are indicated by IED’s and biomarkers in the latent period. We hypothesize that those pigs that
develop PTE will have greater peripheral plasma biomarkers associated with inflammation and blood
brain barrier opening, greater changes in Cl-o and Cl-I, and faster development of hypersynchronous
local and global network activity (EEG).
The is approach is innovative in that, we bring cell imaging technology developed in rodent and
organotypic culture models and newly developed algorithms to the gyrencephalic brain merging the
fields of high technology and large animal models. Our contribution is significant as tools and
biomarkers will enable wider use of gyrencephalic models of PTE and prediction of PTE will open up
large fields of study not yet possible. Understanding the extracellular-matrix-induced changes that alter
the ionic bases of GABAergic signaling and local and global network changes in the same subjects
during the course of epileptogenesis may identify mechanisms of epileptogenesis that serve as targets
for therapies that may prevent the development of PTE.

## Key facts

- **NIH application ID:** 10896227
- **Project number:** 5P01NS127769-02
- **Recipient organization:** MASSACHUSETTS GENERAL HOSPITAL
- **Principal Investigator:** Beth A Costine-Bartell
- **Activity code:** P01 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2024
- **Award amount:** $251,558
- **Award type:** 5
- **Project period:** 2023-08-01 → 2028-04-30

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/10896227

## Citation

> US National Institutes of Health, RePORTER application 10896227, A Biofidelic Model of PTE (Project 1) (5P01NS127769-02). Retrieved via AI Analytics 2026-05-24 from https://api.ai-analytics.org/grant/nih/10896227. Licensed CC0.

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