Nutraceutical Induction and Mimicry of Heme Oxygenase Activity as a Strategy for Controlling Excitotoxicity in Brain Trauma and Ischemic Stroke: Focus on Oxidative Stress.

Nutraceutical Induction and Mimicry of Heme Oxygenase Activity as a Strategy for Controlling Excitotoxicity in Brain Trauma and Ischemic Stroke: Focus on Oxidative Stress. Expert Rev Neurother. 2020 Dec 08;: Authors: McCarty MF, Lerner A Abstract Introduction: Ischemic stroke and traumatic brain injury are leading causes of acute mortality, and in the longer run, major causes of significant mental and physical impairment. Most of the brain neuronal cell death in the minutes and hours following an ischemic stroke or brain trauma is mediated by the process of excitotoxicity, in which sustained elevations of extracellular glutamate, reflecting a failure of ATP-dependent mechanism which sequester glutamate in neurons and astrocytes, drive excessive activation of NMDA receptors. Areas covered: A literature search was undertaken to clarify the molecular mechanisms whereby excessive NMDA activation leads to excitotoxic neuronal death, and to determine what safe nutraceutical agents might have practical potential for rescuing at-risk neurons by intervening in these mechanisms. Expert opinion: Activation of both NADPH oxidase and neuronal nitric oxide synthase in the microenvironment of activated NMDA receptors drives production of superoxide and highly toxic peroxynitrite. This leads to excessive activation of PARP and p38 MAP kinase, mitochondrial dysfunction, and subsequent neuronal death. Heme oxygenase-1 (HO-1) induction offers protection via inhibition of N...
Source: Expert Review of Neurotherapeutics - Category: Neurology Tags: Expert Rev Neurother Source Type: research