Post‐Cardiac Arrest Neurological Injury is Associated with Neuroinflammation and Mitochondrial Respiratory Deficiency

Abstract

Background Cardiopulmonary resuscitation (CPR) following sudden cardiac death is associated with neurological injury but the pathophysiology of this injury remains poorly understood. In this study we investigated the effects of post‐cardiac arrest CPR on neurological outcomes and hypothesized that injury would be associated with neuroinflammation and central nervous system mitochondrial injury. Method C57BL/6 adult mice underwent either asystolic cardiac arrest (CA) (N=19) followed by CPR or sham operation (SHAM) (N=12). Neurobehavioral assessment and survival analysis were made in animals following CPR. Brain tissue was harvested from both SHAM and CA mice for brain slice electrophysiological studies, microglial morphometric analysis, and mitochondrial respiration measurements. Results Post‐CA neurological injury was evident as evaluated by neurological scores (difference of 3.626 ± 0.4921, 95%CI 2.618‐4.634), sensory scores (difference of ‐65.79 ± 14.7 seconds, 95%CI ‐96.21 to ‐35.37), motor scores (difference of ‐107.2 ± 6.558 seconds, 95%CI ‐120.7 to ‐93.61) and video analysis of distance (mean difference of 8.361 meters ± 0.5061, 95%CI 10.52 to 6.203) and speed (difference of 0.0689 m/s ± 0.004242, 95%CI 0.08715 to 0.05065). 24 hours post‐CA, synaptic long‐term potentiation (LTP) and maximal mitochondrial oxygen consumption (OCR) (mean difference ‐107.4 ± 37.79 pmol/min, p=0.0467, N=3/group) were depressed. These outcomes were also associated with morphometric changes in microglia. Microglia demonstrated shorter process lengths per soma (mean difference of 139.5 ± 29.62, p=0.0013, N=4/group) as well as less process endpoints per soma (mean difference of 42.21 ± 9.123, p=0.0018, N=4/group) compared to control microglia, suggesting post‐CA microglial activation. Conclusion These results indicate that neurological injury following post‐CA CPR is associated with impaired synaptic plasticity, depressed mitochondrial respiration, and neuroinflammation. Future studies evaluating the basis and interactions of these post‐CA phenomena are warranted.