79eede1666a4769165d9ec1d133a3cce pmc_34769328.pdf af02bcb4d45cbc196bee0b230f6c714e99d5d493 pmc_34769328.pdf 38a18709dd5a1523ec4068a7eef937b89a94e6071d6d7eead83f2f2f65a0ee13 pmc_34769328.pdf Title: Sulfonylurea Receptor 1 in Central Nervous System Injury: An Updated Review Subject: Sulfonylurea receptor 1 (SUR1) is a member of the adenosine triphosphate (ATP)-binding cassette (ABC) protein superfamily, encoded by Abcc8, and is recognized as a key mediator of central nervous system (CNS) cellular swelling via the transient receptor potential melastatin 4 (TRPM4) channel. Discovered approximately 20 years ago, this channel is normally absent in the CNS but is transcriptionally upregulated after CNS injury. A comprehensive review on the pathophysiology and role of SUR1 in the CNS was published in 2012. Since then, the breadth and depth of understanding of the involvement of this channel in secondary injury has undergone exponential growth: SUR1-TRPM4 inhibition has been shown to decrease cerebral edema and hemorrhage progression in multiple preclinical models as well as in early clinical studies across a range of CNS diseases including ischemic stroke, traumatic brain injury, cardiac arrest, subarachnoid hemorrhage, spinal cord injury, intracerebral hemorrhage, multiple sclerosis, encephalitis, neuromalignancies, pain, liver failure, status epilepticus, retinopathies and HIV-associated neurocognitive disorder. Given these substantial developments, combined with the timeliness of ongoing clinical trials of SUR1 inhibition, now, another decade later, we review advances pertaining to SUR1-TRPM4 pathobiology in this spectrum of CNS disease—providing an overview of the journey from patch-clamp experiments to phase III trials. Keywords: sulfonylurea receptor; edema; cellular swelling; traumatic brain injury; stroke; SUR 1; TRPM4; clinical trials Author: Ruchira M. Jha, Anupama Rani, Shashvat M. Desai, Sudhanshu Raikwar, Sandra Mihaljevic, Amanda Munoz-Casabella, Patrick M. Kochanek, Joshua Catapano, Ethan Winkler, Giuseppe Citerio, J. Claude Hemphill, W. Taylor Kimberly, Raj Narayan, Juan Sahuquillo, Kevin N. Sheth and J. Marc Simard Creator: LaTeX with hyperref Producer: pdfTeX-1.40.21 CreationDate: Thu Nov 4 06:12:38 2021 CET ModDate: Thu Nov 4 06:28:32 2021 CET Tagged: no UserProperties: no Suspects: no Form: none JavaScript: no Pages: 62 Encrypted: no Page size: 595.276 x 841.89 pts (A4) Page rot: 0 File size: 27264615 bytes Optimized: no PDF version: 1.7 name type encoding emb sub uni object ID ------------------------------------ ----------------- ---------------- --- --- --- --------- CAPTPV+VnURWPalladioL Type 1 Custom yes yes no 10 0 RYPSTL+URWPalladioL-Ital Type 1 Custom yes yes no 15 0 DKREXV+URWPalladioL-Bold Type 1 Custom yes yes no 20 0 HRIKVS+URWPalladioL-Roma Type 1 Custom yes yes no 24 0 IRWHZX+TimesNewRomanPSMT Type 1C WinAnsi yes yes no 32 0 CKUPDE+TimesNewRomanPS-BoldItalicMT Type 1C WinAnsi yes yes no 35 0 MCBCCI+SourceSansRoman-Regular Type 1C Custom yes yes no 57 0 MCBCCM+SourceSansRoman.613wght Type 1C Custom yes yes no 61 0 MCBCCO+SourceSansRoman-Bold Type 1C Custom yes yes no 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Jha, Anupama Rani, Shashvat M. Desai, Sudhanshu Raikwar, Sandra Mihaljevic, Amanda Munoz-Casabella, Patrick M. Kochanek, Joshua Catapano, Ethan Winkler, Giuseppe Citerio, J. Claude Hemphill, W. Taylor Kimberly, Raj Narayan, Juan Sahuquillo, Kevin N. Sheth and J. Marc Simard Subject: Sulfonylurea receptor 1 (SUR1) is a member of the adenosine triphosphate (ATP)-binding cassette (ABC) protein superfamily, encoded by Abcc8, and is recognized as a key mediator of central nervous system (CNS) cellular swelling via the transient receptor potential melastatin 4 (TRPM4) channel. Discovered approximately 20 years ago, this channel is normally absent in the CNS but is transcriptionally upregulated after CNS injury. A comprehensive review on the pathophysiology and role of SUR1 in the CNS was published in 2012. Since then, the breadth and depth of understanding of the involvement of this channel in secondary injury has undergone exponential growth: SUR1-TRPM4 inhibition has been shown to decrease cerebral edema and hemorrhage progression in multiple preclinical models as well as in early clinical studies across a range of CNS diseases including ischemic stroke, traumatic brain injury, cardiac arrest, subarachnoid hemorrhage, spinal cord injury, intracerebral hemorrhage, multiple sclerosis, encephalitis, neuromalignancies, pain, liver failure, status epilepticus, retinopathies and HIV-associated neurocognitive disorder. Given these substantial developments, combined with the timeliness of ongoing clinical trials of SUR1 inhibition, now, another decade later, we review advances pertaining to SUR1-TRPM4 pathobiology in this spectrum of CNS disease providing an overview of the journey from patch-clamp experiments to phase III trials. Keywords: sulfonylurea receptor; edema; cellular swelling; traumatic brain injury; stroke; SUR 1; TRPM4; clinical trials Creator: LaTeX with hyperref Producer: pdfTeX-1.40.21 CreationDate: Thu Nov 04 06:12:38 CET 2021 ModDate: Thu Nov 04 06:28:32 CET 2021 ID: 0xe6356b4b6568c767aeb8b2aeec972a6e, 0xe6356b4b6568c767aeb8b2aeec972a6e Filters: FilterPipeline: FlateDecode Fonts: Type1: Font: BaseFont: OMSTLL+CMSY10 FontSubset: true FirstChar: 0 LastChar: 48 FontDescriptor: FontName: OMSTLL+CMSY10 Flags: Symbolic FontBBox: -29, -960, 1116, 775 FontFile: true Font: BaseFont: DKREXV+URWPalladioL-Bold FontSubset: true FirstChar: 2 LastChar: 134 FontDescriptor: FontName: DKREXV+URWPalladioL-Bold Flags: Symbolic FontBBox: -152, -301, 1000, 935 FontFile: true EncodingDictionary: Differences: true Font: BaseFont: HRIKVS+URWPalladioL-Roma FontSubset: true FirstChar: 2 LastChar: 252 FontDescriptor: FontName: HRIKVS+URWPalladioL-Roma Flags: Symbolic FontBBox: -166, -283, 1021, 943 FontFile: true 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