Sulfonylurea Receptor 1 in Central Nervous System Injury: A Focused Review

• Published in: Journal of Cerebral Blood Flow & Metabolism Vol. 32; no. 9; pp. 1699 - 1717
• Main Authors: Simard, J Marc, Woo, S Kyoon, Schwartzbauer, Gary T, Gerzanich, Volodymyr
• Format: Book Review Journal Article
• Language: English
• Published: London, England SAGE Publications 01-09-2012; Nature Publishing Group; Sage Publications Ltd
• Subjects: Animal models; Animals; ATP-Binding Cassette Transporters - biosynthesis; ATP-Binding Cassette Transporters - drug effects; ATP-Binding Cassette Transporters - metabolism; ATP-Binding Cassette Transporters - physiology; Biological and medical sciences; Blood-Brain Barrier; Brain Injuries - genetics; Brain Injuries - metabolism; Brain Ischemia - genetics; Brain Ischemia - metabolism; Calcium (intracellular); Cell Death; Cell size; Central nervous system; Central Nervous System - injuries; Central Nervous System - metabolism; Cerebral blood flow; Clinical trials; Edema; Gene Expression Regulation - genetics; glibenclamide; Humans; Inflammation; Intravenous administration; Ischemia; Medical sciences; Metabolic diseases; Microvasculature; Necrosis; Neurology; Other metabolic disorders; Pigments (porphyrias, hyperbilirubinemias...); Potassium Channels, Inwardly Rectifying - biosynthesis; Potassium Channels, Inwardly Rectifying - drug effects; Potassium Channels, Inwardly Rectifying - metabolism; Potassium Channels, Inwardly Rectifying - physiology; Receptors, Drug - biosynthesis; Receptors, Drug - drug effects; Receptors, Drug - metabolism; Receptors, Drug - physiology; Review; Reviews; Spinal Cord Injuries - genetics; Spinal Cord Injuries - metabolism; Spinal cord injury; Stroke; Sulfonylurea Receptors; Suppression, Genetic; Traumatic brain injury; Up-Regulation; Vascular diseases and vascular malformations of the nervous system; spinal cord injury; necrotic cell death; cerebral ischemia; subarachnoid hemorrhage; Sur1; traumatic brain injury; glibenclamide; NCCa-ATP channel; Central nervous system; channel; Cardiovascular disease; Vascular disease; Hypoglycemic agent; Spinal cord trauma; Glibenclamide; Cerebrovascular disease; Nervous system diseases; Subarachnoid hemorrhage; Cerebral disorder; Sulfonamides; Cell death; NC; Central nervous system disease; Sulfonylureas; Brain ischemia; Head trauma; Spinal cord disease; ATP
• ISSN: 0271-678X; 1559-7016
• DOI: 10.1038/jcbfm.2012.91

The sulfonylurea receptor 1 (Sur1)-regulated NCCa-ATP channel is a nonselective cation channel that is regulated by intracellular calcium and adenosine triphosphate. The channel is not constitutively expressed, but is transcriptionally upregulated de novo in all cells of the neurovascular unit, in many forms of central nervous system (CNS) injury, including cerebral ischemia, traumatic brain injury (TBI), spinal cord injury (SCI), and subarachnoid hemorrhage (SAH). The channel is linked to microvascular dysfunction that manifests as edema formation and delayed secondary hemorrhage. Also implicated in oncotic cell swelling and oncotic (necrotic) cell death, the channel is a major molecular mechanism of ‘accidental necrotic cell death’ in the CNS. In animal models of SCI, pharmacological inhibition of Sur1 by glibenclamide, as well as gene suppression of Abcc8, prevents delayed capillary fragmentation and tissue necrosis. In models of stroke and TBI, glibenclamide ameliorates edema, secondary hemorrhage, and tissue damage. In a model of SAH, glibenclamide attenuates the inflammatory response due to extravasated blood. Clinical trials of an intravenous formulation of glibenclamide in TBI and stroke underscore the importance of recent advances in understanding the role of the Sur1-regulated NCCa-ATP channel in acute ischemic, traumatic, and inflammatory injury to the CNS.