# Sex differences in brain injury following pediatric cardiac arrest

> **NIH NIH R01** · OHIO STATE UNIVERSITY · 2022 · $74,107

## Abstract

Project Summary
The following aims are developed as the logical next step based on published and unpublished findings from the
parent grant (initiated by the late Dr. Traystman) to assess sex-specific signaling following pediatric (juvenile
mice) cardiac arrest and cardiopulmonary resuscitation (CA/CPR). Pediatric cardiac arrest is surprisingly
common and remains poorly understood and understudied. We made significant progress on the major aims of
the previous grant cycle and obtained important new preliminary data that form the foundation for the current
aims. We take advantage of our novel juvenile mouse cardiac arrest and cardiopulmonary resuscitation
(CA/CPR) model to assess functional outcomes and recovery following CA/CPR. Emerging evidence from our
laboratory, and others, indicate that alterations in the surviving functional networks contribute to cognitive
deficits. Synaptic plasticity, in the form of strengthening following physiological stimuli (long-term potentiation;
LTP) is a well-established cellular model of learning and memory. Deficits in hippocampal LTP correlate with
memory impairments in adult and juvenile mice and therefore, we focus on therapies that target reversing
synaptic plasticity deficit to enhance functional recovery (neuro-restoration). We recently made the
remarkable observation that juvenile mice exhibit endogenous neuro-restoration; recovery LTP
and memory function 14-30 days after CA/CPR, which we do not observe in adults exposed to the
same injury.
 Our data indicates that the impairments and endogenous recovery of synaptic plasticity and memory
function in juvenile mice correlates with expression of brain derived neurotrophic factor (BDNF). Further, we
show that stimulation of BDNF-TrkB signaling facilitates recovery of hippocampal function. The recovery in
hippocampal function we observed in juveniles corresponds with hormonal maturation that occurs between
PND28-56. Our preliminary data indicates that gonadectomy of juvenile male (CAST) and female (OVX) mice
prevents recovery of LTP (and recovery of BDNF levels) following CA/CPR. Further, we observed that
replacement of sex steroids (estrogen in females and testosterone in males) restores endogenous neuro-
restoration in CAST/OVX juvenile mice. Importantly, we observe that estrogen stimulates BDNF expression in
juvenile females but not males and that brain estrogen does not facilitate recovery of LTP in males. Therefore,
our overarching hypothesis is that 1) increased steroid levels in the brain during puberty facilitate endogenous
neuro-restoration following juvenile CA/CPR through activation of sex-specific signaling (Aim 2 male-specific
androgen signaling and aim 3 female-specific estrogen receptor signaling) that converges on BDNF and other
plasticity gene expression to enhance synaptic plasticity. The proposed research will contribute to our
understanding of the mechanisms of functional impairments and recovery following cardiac arrest in the
pediatric ...

## Key facts

- **NIH application ID:** 10542297
- **Project number:** 3R01NS046072-19S1
- **Recipient organization:** OHIO STATE UNIVERSITY
- **Principal Investigator:** Paco S Herson
- **Activity code:** R01 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2022
- **Award amount:** $74,107
- **Award type:** 3
- **Project period:** 2002-09-30 → 2025-01-31

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/10542297

## Citation

> US National Institutes of Health, RePORTER application 10542297, Sex differences in brain injury following pediatric cardiac arrest (3R01NS046072-19S1). Retrieved via AI Analytics 2026-05-23 from https://api.ai-analytics.org/grant/nih/10542297. Licensed CC0.

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