Best practice & research. Clinical anaesthesiology
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The endpoint of all cerebral injuries like stroke, global cerebral ischemia during cardiac arrest, cardiac, vascular, or brain surgery or head trauma is the inadequate supply of the brain with oxygen and glucose, which triggers a characteristic pathophysiologic cascade leading to neuronal death. Many methods and agents have been investigated to produce neuroprotection from cerebral ischemia along this cascade (e.g., hypothermia, anaesthetics, free radical scavengers, excitatory amino acid antagonists, calcium channel blockers, ionic pump modulators, growth factors, heparinization, antineutrophil/platelet factors, steroids, and gene products). However, essentially none of the pharmacological approaches was identified as useful in humans though most agents have been successfully tested in animal models. ⋯ The most important strategy is profound knowledge on cerebral physiology and homeostasis in health and disease. This review discusses essential physiological mechanisms to warrant adequate supply of glucose and oxygen to the brain. In addition, the influence of potential neuroprotective strategies and agents are reviewed in the perioperative setting.
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Multiple sclerosis (MS) is the most common chronic inflammatory disease of the central nervous system which is characterized by inflammatory demyelination and neurodegeneration. Neurological symptoms include sensory disturbances, optic neuritis, limb weakness, ataxia, bladder dysfunction, cognitive deficits and fatigue. ⋯ Currently, Glatiramer acetate (GA) and the interferon-β (IFN-β) variants are established as first-line disease modifying treatments that reduce the relapse rate, ameliorate relapse severity and delay the progression of disability in patients with relapsing-remitting MS. Similarily, sphingosine-1-phosphate (S1P) receptor agonists which influence lymphocyte migration through T cells-trapping in secondary lymphatic organs ameliorates astrogliosis and promotes remyelination by acting on S1P-receptors on astrocytes and oligodendrocytes. Ion channel blockers (e.g. sodium channel blockers), currently used for other indications, are now tested in neurodegenerative diseases to restore intracellular ion homeostasis in neurons. Axonal degeneration was significantly reduced and functional outcome was improved during treatment with Phenytoin, Flecainide and Lamotrigine. Although evidence for a direct protective effect on axons is still missing, additional immune-modulatory actions of sodium channel blockers on microglia and macrophages are likely available. In vitro-studies in axons subjected to anoxia in vitro or exposure to elevated levels of nitric oxide (NO) in vivo demonstrated the involvement of a direct effect on axons. As increased intracellular calcium levels contribute to axonal damage through activation of different enzymes such as proteases, blockade of voltage gated calcium channels is another promising target. For example, nitrendipin and bepridil ameliorate axonal loss and clinical symptoms in different models of chronic neurodegeneration. In addition to these exogenous neuroprotective patheways, endogenous neuroprotective mechanisms including neurotrophins, (re)myelination and, neurogenesis support restauration of neuronal integrity.
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Best Pract Res Clin Anaesthesiol · Dec 2010
ReviewPreconditioning and postconditioning for neuroprotection: the most recent evidence.
Stroke is a leading cause of morbidity and mortality, with perioperative stroke being an important complication in the practice of anaesthesia. Unfortunately, pharmacological treatment options are very limited and often not applicable in the perioperative period. The notion of applying a subtoxic stimulus prior to an otherwise lethal event is termed preconditioning. The main focus of the article is on describing the different concepts of preconditioning, including remote ischaemic preconditioning and anaesthetic preconditioning, as well as postconditioning and summarizing the most recent discoveries in this exciting field.