# Structural and functional sequelae of neonatal anticonvulsant exposure: drug-seizure interactions

> **NIH NIH R01** · GEORGETOWN UNIVERSITY · 2022 · $470,131

## Abstract

Project Summary
Pharmacotherapy during critical periods of brain development can adversely affect nervous system function.
This poses a challenge for the treatment of neurological disorders, where the underlying illness and the
treatment both may have adverse effects. One example of this is balancing the choice of medication for the
treatment of seizures, one of the most common neurological disorders of infancy. Seizures in neonates are a
common occurrence after hypoxia (or hypoxia-ischemia); these seizures are typically aggressively treated with
anticonvulsant drugs. Hypoxia-induced seizures are associated with a profound increase in risk for later-in-life
seizures, as well as significant developmental delays and intellectual disabilities. However, the outcomes due
to the seizures and the outcomes due to the drug therapy are confounded. In this application, we propose to
evaluate: (1) the effect of hypoxia-induced seizures, (2) the effect of the three most common anti-seizure drugs
used in babies (phenobarbital, phenytoin, levetiracetam), and (3) the efficacy of a neuroprotective intervention
(melatonin). We will determine the degree to which seizures and drugs influence brain development at the level
of biochemistry (assessment of programmed cell death, oxidative stress), neurophysiology (patch-clamp
recordings from neurons in hippocampal CA1 subfield), and behavior (tests of learning and memory in adult
animals exposed to drugs and/or seizures as babies). We will also evaluate biomarkers of drug safety through
peripheral measurement of oxidative stress and high-resolution magnetic resonance imaging of animals
exposed to these early life insults. Finally, we will determine if our neuroprotective intervention ameliorates
some, or all, of the adverse outcomes associated with seizures and/or drug treatment.

## Key facts

- **NIH application ID:** 10454335
- **Project number:** 5R01HD091994-05
- **Recipient organization:** GEORGETOWN UNIVERSITY
- **Principal Investigator:** Patrick Alexander Forcelli
- **Activity code:** R01 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2022
- **Award amount:** $470,131
- **Award type:** 5
- **Project period:** 2018-09-01 → 2024-06-30

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/10454335

## Citation

> US National Institutes of Health, RePORTER application 10454335, Structural and functional sequelae of neonatal anticonvulsant exposure: drug-seizure interactions (5R01HD091994-05). Retrieved via AI Analytics 2026-05-23 from https://api.ai-analytics.org/grant/nih/10454335. Licensed CC0.

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