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

Santosh K. Sanganalmath, Purva Gopal, John R. Parker, Richard K. Downs, Joseph C. Parker, Buddhadeb Dawn

Research output: Contribution to journalArticle

17 Scopus citations

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, Ca2+ 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.

Original languageEnglish (US)
Pages (from-to)1-17
Number of pages17
JournalMolecular and Cellular Biochemistry
DOIs
StateAccepted/In press - Nov 28 2016

Keywords

  • Biomarkers
  • Cellular mechanism
  • Cerebral ischemia
  • Hypothermia
  • Neuroimaging

ASJC Scopus subject areas

  • Molecular Biology
  • Clinical Biochemistry
  • Cell Biology

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