A systematic review of neuroprotective strategies after cardiac arrest: from bench to bedside (Part I – Protection via specific pathways)

Abstract

Neurocognitive deficits are a major source of morbidity in survivors of cardiac arrest. Treatment options that could be implemented either during cardiopulmonary resuscitation or after return of spontaneous circulation to improve these neurological deficits are limited. We conducted a literature review of treatment protocols designed to evaluate neurologic outcome and survival following cardiac arrest with associated global cerebral ischemia. The search was limited to investigational therapies that were utilized to treat global cerebral ischemia associated with cardiac arrest. In this review we discuss potential mechanisms of neurologic protection following cardiac arrest including actions of several medical gases such as xenon, argon, and nitric oxide. The 3 included mechanisms are: 1. Modulation of neuronal cell death; 2. Alteration of oxygen free radicals; and 3. Improving cerebral hemodynamics. Only a few approaches have been evaluated in limited fashion in cardiac arrest patients and results show inconclusive neuroprotective effects. Future research focusing on combined neuroprotective strategies that target multiple pathways are compelling in the setting of global brain ischemia resulting from cardiac arrest.

The protective effects of distal ischemic treatment on apoptosis and mitochondrial permeability in the hippocampus after cardiopulmonary resuscitation

“…In preclinical and clinical experiments, ischemia pretreatment, concurrent treatment, and post‐processing have been demonstrated to reduce nerve injury after ischemia reperfusion by reducing apoptosis in hippocampal CA1 neurons, thus improving neurological function after CPR (Gonzalez, Connolly, Dusick, Bhakta, & Vespa, ; Hougaard et al, ; Moscarelli, Angelini, Suleiman, Fiorentino, & Punjabi, ; Xu et al, ). The mechanism of action of these interventions may be related to their capacity to reduce mitochondrial damage (Cour et al, ; Mangus et al, ; Segal et al, ). Most of these studies target local cerebral ischemia reperfusion injury (Han et al, ; Li et al, ).…”

Beneficial Effects of a CaMKIIα Inhibitor TatCN21 Peptide in Global Cerebral Ischemia

“…Patients who successfully survive the initial ischemic event are still at a major risk of dying or developing delayed neuronal cell death leading to severe disabilities (Schneider et al , 2009; Mangus et al , 2014). The brain has limited ischemic tolerance due to high consumption of oxygen, restricted anaerobic metabolism, and glycogen stores.…”

Breakthrough in cardiac arrest: reports from the 4th Paris International Conference

“…Although many pathological mechanisms, including endothelial damage and tissue hypoperfusion, inflammation, impaired mitochondrial respiration with induction of reactive oxygen species, calcium overload or excitotoxicity, are common in both cardiac and neurological injury following CA [ 112 ], some drugs may present a more specific organ protection or have a lower brain penetration, thus acting especially on the cardiac tissue. Many therapeutic agents have been shown to be effective in protecting the heart and/or the brain in animal models of global or local ischemia [ 113 ]; nevertheless, these findings were flawed because of the differences between the experimental setting and the clinical scenario (i.e. absence of co-morbid diseases and need for anesthetics in animal studies), the low mortality rates or the administration of the specific drug before the development of injury (i.e.…”