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 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.
Aydin et al. (Sun,) studied this question.