Pharmacologic neuroprotection in ischemic brain injury after cardiac arrest

Abstract

Cardiac arrest has many implications for morbidity and mortality. Few interventions have been shown to improve return of spontaneous circulation (ROSC) and long-term outcomes after cardiac arrest. Ischemic-reperfusion injury upon achieving ROSC creates an imbalance between oxygen supply and demand. Multiple events occur in the postcardiac arrest period, including excitotoxicity, mitochondrial dysfunction, and oxidative stress and inflammation, all of which contribute to ongoing brain injury and cellular death. Given that complex pathophysiology underlies global brain hypoxic ischemia, neuroprotective strategies targeting multiple stages of the neuropathologic cascade should be considered as a means of mitigating secondary neuronal injury and improving neurologic outcomes and survival in cardiac arrest victims. In this review article, we discuss a number of different pharmacologic agents that may have a potential role in targeting these injurious pathways following cardiac arrest. Pharmacologic therapies most relevant for discussion currently include memantine, perampanel, magnesium, propofol, thiamine, methylene blue, vitamin C, vitamin E, coenzyme Q 10 , minocycline, steroids, and aspirin.

Hypothermia versus normothermia after out-of-hospital cardiac arrest: A systematic review and meta-analysis of randomized controlled trials

“…The mean survival of out-of-hospital cardiac arrest (OHCA) is approximately 10% [ 2 ], and the mean survival in-hospital cardiac arrest (IHCA) is approximately 25% [ 3 ]. Cardiac arrest survivors have a substantial risk of neurological injury due to hypoxia, ischemia, reperfusion injury, and excitotoxicity [ 4 ]. The current American heart association (AHA) guideline recommends targeted temperature management (TTM) between 32 °C and 36 °C for at least 24 hours for patients unresponsive after OHCA and IHCA for all cardiac rhythms (Class I) [ 5 ].…”

Cross-Talk between Amyloid, Tau Protein and Free Radicals in Post-Ischemic Brain Neurodegeneration in the Form of Alzheimer’s Disease Proteinopathy

“…Oxidative/nitrosative stress in brain ischemia-reperfusion injury also plays a key role in inducing hemorrhagic transformation of the ischemic focus in conjunction with changes in the blood-brain barrier and development of cerebral edema ( Figure 3 ). Research indicates that mitochondrial dysfunction [ 25 , 175 ], metal dyshomeostasis [ 41 , 176 , 177 , 178 ], tau protein hyperphosphorylation [ 123 , 174 ], neuroinflammation and amyloid accumulation [ 106 ] are the primary processes that induce oxidative stress. Inactivation and deficiency of antioxidant enzymes reduces the removal of free radicals from the brain during recirculation.…”

“…Inactivation and deficiency of antioxidant enzymes reduces the removal of free radicals from the brain during recirculation. This indicates that oxidative stress is an important neuropathological hallmark of the post-ischemic brain [ 175 , 179 ].…”

Basic information about memantine and its treatment of Alzheimer's disease and other clinical applications

“…Progression from ischemia–reperfusion injury to neuronal cell death after cardiac arrest is a complex process involving a number of key steps, including excitatory toxicity, mitochondrial dysfunction, oxidative stress, intracellular calcium overload, and overactivation of inflammatory response. Excitotoxicity appears early in the ischemia caused by cardiac arrest and the damage to nerve cells is severe and can further aggravate brain damage, so we need to treat it promptly 40 . Excitotoxicity is associated with excessive activation of excitatory amino acids, mainly glutamate and aspartate.…”