Advances in the Mechanisms Underlying Brain Injury after Resuscitation from Cardiac Arrest
Wenxun Liu, Xiaohong Zhou, Wusheng Liu, Jiaxiang Ren, Wenjuan ZhangIntroduction:
Cardiac arrest (CA) causes global cerebral ischemia. Secondary reperfusion injury frequently worsens neurological dysfunction, making cerebral resuscitation more difficult, even when cardiopulmonary resuscitation (CPR) helps restore spontaneous circulation (ROSC). With an emphasis on early primary ischemic injury and the ensuing reperfusionassociated pathological cascade, this review clarifies the pathophysiological processes of brain injury after CA-CPR.
Methods:
This study reviewed the literature on cerebral pathophysiology following CA-CPR, focusing on studies that explore the mechanisms underlying ischemia, hypoxia, and reperfusion injury. Relevant peer-reviewed articles published between 2016 and 2026 were extracted through searches of PubMed, Embase, and Web of Science. The search keywords included "cardiac arrest," "global cerebral ischemia," "four-vessel occlusion," "asphyxia-induced cardiac arrest," "reperfusion injury," and "neuroprotection." Studies published within the past 5 years were prioritized to reflect recent advancements.
Results:
Multiple interconnected pathways contribute to brain injury, following a distinct temporal sequence from primary ischemic depolarization to secondary reperfusion-induced dysregulation. These include energy metabolism disorders, excitotoxicity, calcium overload, mitochondrial dysfunction, oxidative stress, and neuroinflammation. Furthermore, major neuroprotective strategies are evaluated for their efficacy in mitigating secondary injury.
Discussion:
Cerebral resuscitation is particularly difficult owing to the interplay among these complex mechanisms. Consequently, targeting multiple pathways simultaneously may be more effective than focusing on a single one.
Conclusion:
Brain injury after CA-CPR involves multifactorial pathophysiological processes. Elucidating these mechanisms will establish a groundwork for the development of neuroprotective strategies. However, further research is warranted to translate these findings into clinical practice.