ABSTRACT
Stroke is the second leading cause of death in the world. Unfortunately, only a few drugs have been proved in clinical trials. Drug development of the last decade has been focused substantially on a promising and heterogeneous group of neuroprotective drugs. Hundreds of compounds were suggested as new putative neuroprotectors, which effectiveness was confirmed in preclinical trials only. At the present time discrepancy between results of preclinical studies and clinical trials requires careful analysis. One of the least evaluated and probably the most noticeable reasons is general anesthesia--an obligatory component of an overwhelming majority of existing animal stroke models. The aim of the review is to describe known mechanisms of common general anesthetics influence on ionotropic and metabotropic plasma membrane receptors, and key signal pathways involved in neuronal hypoxic-ischemic injury and survival.
Subject(s)
Anesthetics, Inhalation/pharmacology , Anesthetics, Intravenous/pharmacology , Artifacts , Brain Ischemia/genetics , Neuroprotective Agents/pharmacology , Stroke/genetics , Animals , Apoptosis/drug effects , Brain Ischemia/drug therapy , Brain Ischemia/metabolism , Brain Ischemia/pathology , Disease Models, Animal , Gene Expression Regulation , Humans , Neurons/drug effects , Neurons/metabolism , Neurons/pathology , Receptors, AMPA/genetics , Receptors, AMPA/metabolism , Receptors, GABA/genetics , Receptors, GABA/metabolism , Receptors, Metabotropic Glutamate/genetics , Receptors, Metabotropic Glutamate/metabolism , Receptors, Purinergic P1/genetics , Receptors, Purinergic P1/metabolism , Stroke/drug therapy , Stroke/metabolism , Stroke/pathologyABSTRACT
Influence of alpha-lipoic acid (LA) on liver glutathione system of Ehrlich ascites carcinoma (EAC) transplanted mice was studied. LA causes multidirectional influence on glutathione system of healthy mice. EAC transforms LA influence, strengthening prooxidative effects more expressed at introduction in early terms after inoculation of the tumor. The mechanism explaining realization of LA prooxidative effects as a result of interaction with glutathione system is suggested.
