Evolving therapeutic approaches to treating acute ischemic stroke.
Stroke contributes significantly to death, disability, and healthcare costs; however, recombinant tissue plasminogen activator (rt-PA) is the only approved thrombolytic therapy for acute ischemic stroke. One area of development for new ischemic stroke treatment options is focused on neuroprotection of viable tissue in the ischemic vascular bed. The ischemic penumbra is recognizable on MRI by decreased perfusion, in contrast to the core area of ischemia, which includes diffusion and perfusion abnormalities. Understanding the mechanisms of neuronal death, including the role of excitotoxic neurotransmitters, free radical production, and apoptotic pathways, is important in developing new therapies for stroke. This article reviews these causes and results of stroke, as well as current and future neuroprotective treatment options. Several compounds have shown neuroprotective effects in animal studies, but have failed to be effective in human clinical trials. Several promising therapeutic areas include targeting of free radicals, modulation of glutamatergic transmission, and membrane stabilization via ion channels.
Weinberger
Jesse M
JM
Mt. Sinai School of Medicine, One Gustave L. Levy Place, Box 1139, New York, NY 10029, United States. jesse.weinberger@mssm.edu
D000777:Anesthetics / Q000627:therapeutic use; D000818:Animals; D000927:Anticonvulsants / Q000627:therapeutic use; D000975:Antioxidants / Q000627:therapeutic use; D002545:Brain Ischemia / Q000188:drug therapy* / Q000503:physiopathology / Q000628:therapy; D002121:Calcium Channel Blockers / Q000627:therapeutic use; D002395:Catecholamines / Q000502:physiology; D016923:Cell Death; D005343:Fibrinolytic Agents / Q000627:therapeutic use; D016166:Free Radical Scavengers / Q000627:therapeutic use; D018698:Glutamic Acid / Q000502:physiology; D006801:Humans; D007036:Hypothermia, Induced; D009474:Neurons / Q000187:drug effects / Q000473:pathology; D018696:Neuroprotective Agents / Q000627:therapeutic use*; D009569:Nitric Oxide / Q000502:physiology; D018384:Oxidative Stress; D051381:Rats; D017382:Reactive Oxygen Species / Q000378:metabolism; D017470:Receptors, Glutamate / Q000187:drug effects; D016194:Receptors, N-Methyl-D-Aspartate / Q000502:physiology; D011994:Recombinant Proteins / Q000627:therapeutic use; D015424:Reperfusion; D015912:Thrombolytic Therapy; D010959:Tissue Plasminogen Activator / Q000627:therapeutic use
D000777:Anesthetics; D000927:Anticonvulsants; D000975:Antioxidants; D002121:Calcium Channel Blockers; D002395:Catecholamines; D005343:Fibrinolytic Agents; D016166:Free Radical Scavengers; D018696:Neuroprotective Agents; D017382:Reactive Oxygen Species; D017470:Receptors, Glutamate; D016194:Receptors, N-Methyl-D-Aspartate; D011994:Recombinant Proteins; D009569:Nitric Oxide; D018698:Glutamic Acid; D010959:Tissue Plasminogen Activator