# Sex differences in brain injury following pediatric cardiac arrest

> **NIH NIH R01** · UNIVERSITY OF COLORADO DENVER · 2021 · $8,257

## Abstract

From Parent Award
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The following aims are developed as the logical next step based on published and unpublished findings from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 arre...

## Key facts

- **NIH application ID:** 10302935
- **Project number:** 3R01NS046072-17S1
- **Recipient organization:** UNIVERSITY OF COLORADO DENVER
- **Principal Investigator:** Paco S Herson
- **Activity code:** R01 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2021
- **Award amount:** $8,257
- **Award type:** 3
- **Project period:** 2002-09-30 → 2021-05-31

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/10302935

## Citation

> US National Institutes of Health, RePORTER application 10302935, Sex differences in brain injury following pediatric cardiac arrest (3R01NS046072-17S1). Retrieved via AI Analytics 2026-05-24 from https://api.ai-analytics.org/grant/nih/10302935. Licensed CC0.

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