Global cerebral ischemia due to circulatory arrest: insights into cellular pathophysiology and diagnostic modalities

Abstract

Circulatory arrest (CA) remains a major unresolved public health problem in the United States; the annual incidence of which is ~0.50 to 0.55 per 1000 population. Despite seminal advances in therapeutic approaches over the past several decades, brain injury continues to be the leading cause of morbidity and mortality after CA. In brief, CA typically results in global cerebral ischemia leading to delayed neuronal death in the hippocampal pyramidal cells as well as in the cortical layers. The dynamic changes occurring in neurons after CA are still unclear, and predicting these neurological changes in the brain still remains a difficult issue. It is hypothesized that the "no-flow" period produces a cytotoxic cascade of membrane depolarization, Ca ion influx, glutamate release, acidosis, and resultant activation of lipases, nucleases, and proteases. Furthermore, during reperfusion injury, neuronal death occurs due to the generation of free radicals by interfering with the mitochondrial respiratory chain. The efficacy of many pharmacological agents for CA patients has often been disappointing, reflecting our incomplete understanding of this enigmatic disease. The primary obstacles to the development of a neuroprotective therapy in CA include uncertainties with regard to the precise cause(s) of neuronal dysfunction and what to target. In this review, we summarize our knowledge of the pathophysiology as well as specific cellular changes in brain after CA and revisit the most important neurofunctional, neuroimaging techniques, and serum biomarkers as potent predictors of neurologic outcome in CA patients.

Ischemia-Triggered Glutamate Excitotoxicity From the Perspective of Glial Cells

“…GCI results from transient cardiac arrest causing a systemic and complete cessation of blood flow in the whole parenchyma of the brain (Harukuni and Bhardwaj, 2006), which then diminishes the number of neuronal and glial cells and reduces the integrity of the blood-brain barrier (BBB; Sanganalmath et al, 2017). This type of ischemic injury is characterized by delayed neuronal death in specific brain regions of the brain (Kirino and Sano, 1984;Anderova et al, 2011) and by the proliferation and activation of glial cells (Anderova et al, 2011).…”

Hypothermic properties of dexmedetomidine provide neuroprotection in rats following cerebral ischemia‑reperfusion injury

“…Mortality and morbidity rates as a result of cardiac arrest (CA) remain high despite steady advances in therapeutic approaches over the past decades (1). Post-resuscitation neurological dysfunction is a major cause of mortality in patients following successful cardiopulmonary resuscitation (CPR) (2,3).…”

Spreading depolarization and repolarization during cardiac arrest as an ultra-early marker of neurological recovery in a preclinical model

“…Specifically, animals with less total CBF prior to RP have better outcome. As during entry into CA, a flow-metabolism mismatch may lead to reperfusion injury, potentially by formation of reactive oxygen species, 90 worsening neurological recovery. This theory is supported by our data that rats with worse neurological recovery had greater total perfusion (MAP AUC, CBF AUC) from ROSC to RP.…”