Early Neurodegeneration in an Experimental Model of Pediatric Cardiac Arrest Is Sex Dependent

Monday, March 23, 2026

11:30 AM - 12:30 PM Central Time

Location: Connections Central - RST 07

Elber Aydin, MD (he/him/his)

University of Pittsburgh School of Medicine, Pennsylvania

Disclosure(s): No relevant financial relationship(s) to disclose.
JS

Jason Stezoski, n/a

Research Technician
Safar Center for Resuscitation Research, University of Pittsburgh, Pittsburgh, PA 15224, USA

Disclosure information not submitted.
CJ

Carla Johnson, N/A

Laboratory Manager
Safar Center for Resuscitation Research, University of Pittsburgh, Pittsburgh, PA 15224, USA

Disclosure information not submitted.
KF

Keri Feldman, N/A

Research Technician
Safar Center for Resuscitation Research, University of Pittsburgh, Pittsburgh, PA 15224, USA

Disclosure information not submitted.
KK

Komathi Kanagasan, N/A

Research Technician
Safar Center for Resuscitation Research, University of Pittsburgh, Pittsburgh, PA 15224, USA

Disclosure information not submitted.
PK

Patrick Kochanek, MD, MCCM

Director of the Safar Center for Resuscitation Research
Department of Critical Care Medicine, Safar Center for Resuscitation Research, John G. Rangos Research Center, UPMC Children’s Hospital of Pittsburgh, University of Pittsburgh School of Medicine, Pittsburgh, PA 15224, USA

Disclosure information not submitted.
TJ

Travis Jackson, PhD

Associate Professor
University of South Florida, Department of Molecular Pharmacology & Physiology, Tampa, FL, USA

Disclosure information not submitted.
RC

Robert Clark, MD

Professor of Pediatric Critical Care Medicine, Endowed Chair of Pediatric Critical Care Medicine
Department of Critical Care Medicine, Safar Center for Resuscitation Research, John G. Rangos Research Center, UPMC Children’s Hospital of Pittsburgh, University of Pittsburgh School of Medicine, Pittsburgh, PA 15224, USA

Disclosure information not submitted.

Introduction: Neonatal and adult models producing focal hypoxic-ischemic brain injury (i.e. stroke) show sex-dependent neurodegeneration, with males being more vulnerable. Whether sex-differences also occur in models of global ischemia, such as seen after cardiac arrest, is unknown. We hypothesized that like focal ischemia, males would have more neurodegeneration than females after asphyxial cardiac arrest (ACA) in juvenile postnatal day 17 (PND17) rats.

Methods: Anesthetized male and female PND17 Sprague-Dawley rats were endotracheally intubated and mechanically ventilated and femoral arterial and venous catheters placed. Vecuronium was administered i.v. and ventilation was discontinued to induce ACA. After 14 minutes, return of spontaneous circulation was achieved with chest compressions, epinephrine, and resuming ventilation. Shams underwent identical procedures but no ACA. Neurological Deficit Scores (NDS) were recorded on d 1-7 then rats were sacrificed by perfusion fixation. Brains were paraffin-embedded and 10 micrometer coronal sections that included the dorsal hippocampus were processed for histological evaluation using H&E and fluorojade B (FJB) staining, and Iba1 immunohistochemistry.

Results: ACA resulted in significant neurodegeneration in the selectively vulnerable CA1 hippocampus at 7 d in both male and female rats vs. shams assessed by H&E and FJB as indicators of neuronal survival and neurodegeneration, respectively; neuroinflammation assessed by Iba1 staining of reactive microglia; and worse NDS on d1-3 (n=6/group; ANOVA-Fisher’s LSD; all p< 0.05). Female vs. male rats showed reduced CA1 neuron survival (56±11 vs. 89±30 neurons/mm), increased neurodegeneration (47±8 vs. 13±18 FJB+ neurons/mm), and increased neuroinflammation (48±13 vs. 15±21 Iba1+ neurons/mm) (n=3/sex/group, mean±SD, ANOVA-Fisher’s LSD; all p< 0.05). There was no sex difference in NDS.

Conclusions: Contrary to our initial hypothesis, juvenile female rats had increased neurodegeneration and neuroinflammation vs. male rats 7d post-insult. These findings warrant additional studies with larger sample sizes to verify sex-dependent differences in vulnerability to global hypoxia-ischemia produced by ACA, and long term histologic and behavioral outcome assessments to determine if this vulnerability is enduring.