Histologic evaluation of the cerebral cortex and thalamus in a ventricular fibrillation cardiac arrest rat model

Out of hospital cardiac arrest (OHCA) is a leading cause of death in developed countries and entails a sudden cardiovascular failure and, subsequently, a deficient perfusion. The brain is particularly vulnerable to hypoxia and suffers from permanent damage after only a few minutes. Patients who survive cardiac arrest often develop neurocognitive disorders due to ischemic and secondary brain injuries. A detailed understanding of the resulting lesions is essential to further develop therapy options and consequently improve the outcome of OHCA. This study focuses on the histological and immunohistochemical examination of the cerebral cortex and thalamus in a ventricular fibrillation cardiac arrest rat model. The aim of this study is to quantify neuronal, microglial, and astrocytic reactions to cardiac arrest within the regions of interest. Male Sprague-Dawley rats underwent ventricular fibrillation cardiac arrest (VFCA) for either six or eight minutes followed by extracorporeal cardiopulmonary resuscitation. Fourteen days post cardiac arrest, the surviving animals (sham n = 10; 6-minute VFCA n = 10; 8-minute VFCA n = 5) were sacrificed and compared to each other. To quantify neurons, paraffin sections were stained with hematoxylin and eosin (HE), and for immunohistochemistry, antibodies against Hexaribonucleotide Binding Protein-3 (NeuN) were used. Antibodies against ionized calcium-binding adapter molecule 1 (Iba1) and glial fibrillary acidic protein (GFAP) were applied to quantify the glial reaction. QuPath was used for the analysis. The cerebral cortex of 6-minute VFCA animals contained more viable neurons than the one of sham and 8-minute VFCA animals. No differences in the number of Iba1-positive pixels were found between the three study groups. The 6-minute VFCA animals showed significantly more GFAP-positive pixels than the sham-operated animals. Interestingly, no significant increase was detected in the 8-minute VFCA group. In the thalamus, no difference in the number of viable neurons between the study groups was observed. However, more Iba1 and GFAP-positive pixels were detected in both VFCA groups. Even though only the increase of immunoreactive astrocytes was statistically significant, the median of Iba1-positive pixels mirrored the same trend. The results indicate that adult neurogenesis might have occurred in the cortex of the six-minute VFCA rats but not in the eight-minute VFCA group. This suggests that the prolonged duration of VFCA led to increased damage to the neuronal progenitor cells. The findings indicate a correlation between ischemic insults and distinct immunoreactive glial reactions in the thalamus. Contextualizing these findings with previous studies suggests varying vulnerabilities among the thalamic sub-regions and that further studies are necessary to investigate the selective vulnerability of specific thalamic areas to cardiac arrest.