Voxel-based morphometry and histological analysis for evaluating hippocampal damage in a rat model of cardiopulmonary resuscitation

Abstract

Cardiac arrest and subsequent cardiopulmonary resuscitation (CPR) induce hippocampal damage, which has been identified using histological analysis of post-mortem brains. Voxel-based morphometry (VBM), an in-vivo assessment of regional differences in the concentration or volume of a particular tissue such as gray matter, has revealed CPR-induced decreases in gray matter in the hippocampus, where histopathological findings were observed. However, the potential link between the changes in gray matter detected by VBM and hippocampal damage has not been investigated directly. In this study, we compared results obtained using VBM directly to results from histological analyses in the same CPR rat brains, which exhibited neuronal loss and microglial invasion in the CA1 region of the hippocampus (CA1). T2-weighted images were obtained and preprocessed for VBM to produce gray matter concentration (GMC) maps in rats with asphyxia-induced cardiac arrest and CPR and sham-operated controls (n=12 each). Brains were fixed, and the number of neurons and microglia in CA1 were counted. VBM revealed a significant decrease in GMC in CPR rats compared to sham-operated controls. The CPR-induced decrease in GMC was localized to CA1, which is the same brain region where neuronal loss and microglial invasion were noted in response to CPR. GMC values were positively correlated with the number of neurons and tended to be negatively correlated with the number of microglia in CA1 of CPR rats. In conclusion, these results indicate that VBM-detected alterations in gray matter can be used as a surrogate marker for hippocampal damage following CPR.