Hypoxic-ischemic brain injury in pig after cardiac arrest - A new histopathological scoring system for non-specialists

Introduction: After cardiac arrest and successful resuscitation patients often present with hypoxic-ischemic brain injury, which is a major cause of death due to poor neurological outcome. The development of a robust histopathological scoring system for the reliable and easy identification and quantification of hypoxic-ischemic brain injury could lead to a standardization in the evaluation of brain damage. We wanted to establish an easy-to-use neuropathological scoring system to identify and quantify hypoxic-ischemic brain injury. Methods: The criteria for regular neurons, hypoxic-ischemic brain injury neurons and neurons with ischemic neuronal change (ischemic change neurons) were established in collaboration with specialized neuropathologists. Nine non-specialist examiners performed cell counting using the mentioned criteria in brain tissue samples from a porcine cardiac arrest model. The statistical analyses were performed using the interclass correlation coefficient for counting data and reliability testing. Results: The inter-rater reliability for regular neurons (ICC 0.68 (0.42 - 0.84; p < 0.001) and hypoxic-ischemic brain injury neurons (ICC 0.87 (0.81 - 0.92; p < 0.001) showed moderate to excellent correlation while ischemic change neurons showed poor reliability. Excellent results were seen for intra-rater reliability for regular neurons (ICC 0.9 (0.68 - 0.97; p < 0.001) and hypoxic-ischemic brain injury neurons (ICC 0.99 (0.83 - 1; p < 0.001). Conclusion: The scoring system provides a reliable method for the discrimination between regular neurons and neurons affected by hypoxic/ischemic injury. This scoring system allows an easy and reliable identification and quantification of hypoxic-ischemic brain injury for non-specialists and offers a standardization to evaluate hypoxic-ischemic brain injury after cardiac arrest.