a2201c3fe73bb77d28d0a0c1d7f0fcb3 pmc_31936452.pdf 0d8b9617027d02f3bf27fcff791d0dd16fff0283 pmc_31936452.pdf 055b4d58b39c2599dae5afee4c9a57ce63599a1f14016ed51451ea575a42d28b pmc_31936452.pdf Title: Role of Sulfonylurea Receptor 1 and Glibenclamide in Traumatic Brain Injury: A Review of the Evidence Subject: Cerebral edema and contusion expansion are major determinants of morbidity and mortality after TBI. Current treatment options are reactive, suboptimal and associated with significant side effects. First discovered in models of focal cerebral ischemia, there is increasing evidence that the sulfonylurea receptor 1 (SUR1)—Transient receptor potential melastatin 4 (TRPM4) channel plays a key role in these critical secondary injury processes after TBI. Targeted SUR1-TRPM4 channel inhibition with glibenclamide has been shown to reduce edema and progression of hemorrhage, particularly in preclinical models of contusional TBI. Results from small clinical trials evaluating glibenclamide in TBI have been encouraging. A Phase-2 study evaluating the safety and efficacy of intravenous glibenclamide (BIIB093) in brain contusion is actively enrolling subjects. In this comprehensive narrative review, we summarize the molecular basis of SUR1-TRPM4 related pathology and discuss TBI-specific expression patterns, biomarker potential, genetic variation, preclinical experiments, and clinical studies evaluating the utility of treatment with glibenclamide in this disease. Keywords: SUR1 (Sulfonylurea receptor 1); TRPM4 (transient receptor potential melastatin 4); TBI (traumatic brain injury); cerebral edema; contusion expansion; glibenclamide; glyburide; ASTRAL Author: Ruchira M. Jha, Josh Bell, Giuseppe Citerio, J. Claude Hemphill, W. Taylor Kimberly, Raj K. Narayan, Juan Sahuquillo, Kevin N. Sheth and J. 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こさげ〱〭ごげぐき〴〺ぜ〴ぜ〰ぎづふひはどのてぬちねねちぴどはのぜ〴ぜ〰ちのつぜ〴ぜ〰あああぜ〴ぜ〰ぉのぴづでひどぴべぜ〴〩਼㰠⽓ 䝯呯 䐠⡳畢獵扳散瑩潮⸲⸲⸱ Children: Item: Title: ぎづふひはどのてぬちねねちぴどはのぜ〴〩਼㰠⽓ 䝯呯 䐠⡳畢獵扳散瑩潮⸲⸲⸲ Item: Title: あああぜ〴ぜ〰ぉのぴづでひどぴべぜ〴〩਼㰠⽓ 䝯呯 䐠⡳散瑩潮⸳ Item: Title: こさげ〱〭ごげぐき〴ぜ〴ぜ〰ぅへばひづびびどはのぜ〴ぜ〰どのぜ〴ぜ〰ごあぉぜ〴〩਼㰠⽓ 䝯呯 䐠⡳畢獥捴楯渮㌮ㄩ‾㸊⡜㌷㙜㌷㝜〰ぉのっひづちびづつぜ〴ぜ〰こさげ〱ごげぐき〴ぜ〴ぜ〰ぅへばひづびびどはのぜ〴ぜ〰どのぜ〴ぜ〰げはつづのぴぜ〴ぜ〰きはつづぬびぜ〴ぜ〰はてぜ〴ぜ〰ごあぉぜ〴〩਼㰠⽓ 䝯呯 䐠⡳畢獥捴楯渮㌮㈩‾㸊⡜㌷㙜㌷㝜〰ぉのっひづちびづつぜ〴ぜ〰えふねちのぜ〴ぜ〰こさげ〱ごげぐき〴ぜ〴ぜ〰ぅへばひづびびどはのぜ〴ぜ〰どのぜ〴ぜ〰ごあぉぜ〴〩਼㰠⽓ 䝯呯 䐠⡳畢獥捴楯渮㌮㌩‾㸊⡜㌷㙜㌷㝜〰こさげ〱〭ごげぐき〴ぜ〴ぜ〰ごとづひちのはびぴどっぜ〴ぜ〰あどはねちひにづひぜ〴ぜ〰ぐはぴづのぴどちぬぜ〴ぜ〰ちてぴづひぜ〴ぜ〰ごあぉぜ〴〩਼㰠⽓ 䝯呯 䐠⡳畢獥捴楯渮㌮㐩‾㸊⡜㌷㙜㌷㝜〰ぉねばちっぴぜ〴ぜ〰はてぜ〴ぜ〰ぇづのづぴどっぜ〴ぜ〰ざちひどちぴどはのぜ〴ぜ〰どのぜ〴ぜ〰ぁあぃぃ〸ぜ〴ぜ〰ぜ〵ぜ〰ぅのっはつどのでぜ〴ぜ〰こさげ〱ぜ〵ㅜ〰ぜ〴ぜ〰ちのつぜ〴ぜ〰ごげぐき〴ぜ〴ぜ〰どのぜ〴ぜ〰ごあぉぜ〴〩਼㰠⽓ 䝯呯 䐠⡳畢獥捴楯渮㌮㔩‾㸊⡜㌷㙜㌷㝜〰ぐひづっぬどのどっちぬぜ〴ぜ〰こぴふつどづびぜ〴ぜ〰はてぜ〴ぜ〰こさげ〱ぜ〴ぜ〰ぉのとどぢどぴどはのぜ〴ぜ〰どのぜ〴ぜ〰ごあぉぜ〴〩਼㰠⽓ 䝯呯 䐠⡳畢獥捴楯渮㌮㘩‾㸊⡜㌷㙜㌷㝜〰ぃぬどのどっちぬぜ〴ぜ〰こぴふつどづびぜ〴ぜ〰はてぜ〴ぜ〰ぇがぉぜ〴ぜ〰どのぜ〴ぜ〰ごあぉぜ〴〩਼㰠⽓ 䝯呯 䐠⡳散瑩潮⸴ Children: Item: Title: ぉのっひづちびづつぜ〴ぜ〰こさげ〱ごげぐき〴ぜ〴ぜ〰ぅへばひづびびどはのぜ〴ぜ〰どのぜ〴ぜ〰げはつづのぴぜ〴ぜ〰きはつづぬびぜ〴ぜ〰はてぜ〴ぜ〰ごあぉぜ〴〩਼㰠⽓ 䝯呯 䐠⡳畢獥捴楯渮㌮㈩‾㸊⡜㌷㙜㌷㝜〰ぉのっひづちびづつぜ〴ぜ〰えふねちのぜ〴ぜ〰こさげ〱ごげぐき〴ぜ〴ぜ〰ぅへばひづびびどはのぜ〴ぜ〰どのぜ〴ぜ〰ごあぉぜ〴〩਼㰠⽓ 䝯呯 䐠⡳畢獥捴楯渮㌮㌩‾㸊⡜㌷㙜㌷㝜〰こさげ〱〭ごげぐき〴ぜ〴ぜ〰ごとづひちのはびぴどっぜ〴ぜ〰あどはねちひにづひぜ〴ぜ〰ぐはぴづのぴどちぬぜ〴ぜ〰ちてぴづひぜ〴ぜ〰ごあぉぜ〴〩਼㰠⽓ 䝯呯 䐠⡳畢獥捴楯渮㌮㐩‾㸊⡜㌷㙜㌷㝜〰ぉねばちっぴぜ〴ぜ〰はてぜ〴ぜ〰ぇづのづぴどっぜ〴ぜ〰ざちひどちぴどはのぜ〴ぜ〰どのぜ〴ぜ〰ぁあぃぃ〸ぜ〴ぜ〰ぜ〵ぜ〰ぅのっはつどのでぜ〴ぜ〰こさげ〱ぜ〵ㅜ〰ぜ〴ぜ〰ちのつぜ〴ぜ〰ごげぐき〴ぜ〴ぜ〰どのぜ〴ぜ〰ごあぉぜ〴〩਼㰠⽓ 䝯呯 䐠⡳畢獥捴楯渮㌮㔩‾㸊⡜㌷㙜㌷㝜〰ぐひづっぬどのどっちぬぜ〴ぜ〰こぴふつどづびぜ〴ぜ〰はてぜ〴ぜ〰こさげ〱ぜ〴ぜ〰ぉのとどぢどぴどはのぜ〴ぜ〰どのぜ〴ぜ〰ごあぉぜ〴〩਼㰠⽓ 䝯呯 䐠⡳畢獥捴楯渮㌮㘩‾㸊⡜㌷㙜㌷㝜〰ぃぬどのどっちぬぜ〴ぜ〰こぴふつどづびぜ〴ぜ〰はてぜ〴ぜ〰ぇがぉぜ〴ぜ〰どのぜ〴ぜ〰ごあぉぜ〴〩਼㰠⽓ 䝯呯 䐠⡳散瑩潮⸴ Item: Title: ぉのっひづちびづつぜ〴ぜ〰えふねちのぜ〴ぜ〰こさげ〱ごげぐき〴ぜ〴ぜ〰ぅへばひづびびどはのぜ〴ぜ〰どのぜ〴ぜ〰ごあぉぜ〴〩਼㰠⽓ 䝯呯 䐠⡳畢獥捴楯渮㌮㌩‾㸊⡜㌷㙜㌷㝜〰こさげ〱〭ごげぐき〴ぜ〴ぜ〰ごとづひちのはびぴどっぜ〴ぜ〰あどはねちひにづひぜ〴ぜ〰ぐはぴづのぴどちぬぜ〴ぜ〰ちてぴづひぜ〴ぜ〰ごあぉぜ〴〩਼㰠⽓ 䝯呯 䐠⡳畢獥捴楯渮㌮㐩‾㸊⡜㌷㙜㌷㝜〰ぉねばちっぴぜ〴ぜ〰はてぜ〴ぜ〰ぇづのづぴどっぜ〴ぜ〰ざちひどちぴどはのぜ〴ぜ〰どのぜ〴ぜ〰ぁあぃぃ〸ぜ〴ぜ〰ぜ〵ぜ〰ぅのっはつどのでぜ〴ぜ〰こさげ〱ぜ〵ㅜ〰ぜ〴ぜ〰ちのつぜ〴ぜ〰ごげぐき〴ぜ〴ぜ〰どのぜ〴ぜ〰ごあぉぜ〴〩਼㰠⽓ 䝯呯 䐠⡳畢獥捴楯渮㌮㔩‾㸊⡜㌷㙜㌷㝜〰ぐひづっぬどのどっちぬぜ〴ぜ〰こぴふつどづびぜ〴ぜ〰はてぜ〴ぜ〰こさげ〱ぜ〴ぜ〰ぉのとどぢどぴどはのぜ〴ぜ〰どのぜ〴ぜ〰ごあぉぜ〴〩਼㰠⽓ 䝯呯 䐠⡳畢獥捴楯渮㌮㘩‾㸊⡜㌷㙜㌷㝜〰ぃぬどのどっちぬぜ〴ぜ〰こぴふつどづびぜ〴ぜ〰はてぜ〴ぜ〰ぇがぉぜ〴ぜ〰どのぜ〴ぜ〰ごあぉぜ〴〩਼㰠⽓ 䝯呯 䐠⡳散瑩潮⸴ Item: Title: こさげ〱〭ごげぐき〴ぜ〴ぜ〰ごとづひちのはびぴどっぜ〴ぜ〰あどはねちひにづひぜ〴ぜ〰ぐはぴづのぴどちぬぜ〴ぜ〰ちてぴづひぜ〴ぜ〰ごあぉぜ〴〩਼㰠⽓ 䝯呯 䐠⡳畢獥捴楯渮㌮㐩‾㸊⡜㌷㙜㌷㝜〰ぉねばちっぴぜ〴ぜ〰はてぜ〴ぜ〰ぇづのづぴどっぜ〴ぜ〰ざちひどちぴどはのぜ〴ぜ〰どのぜ〴ぜ〰ぁあぃぃ〸ぜ〴ぜ〰ぜ〵ぜ〰ぅのっはつどのでぜ〴ぜ〰こさげ〱ぜ〵ㅜ〰ぜ〴ぜ〰ちのつぜ〴ぜ〰ごげぐき〴ぜ〴ぜ〰どのぜ〴ぜ〰ごあぉぜ〴〩਼㰠⽓ 䝯呯 䐠⡳畢獥捴楯渮㌮㔩‾㸊⡜㌷㙜㌷㝜〰ぐひづっぬどのどっちぬぜ〴ぜ〰こぴふつどづびぜ〴ぜ〰はてぜ〴ぜ〰こさげ〱ぜ〴ぜ〰ぉのとどぢどぴどはのぜ〴ぜ〰どのぜ〴ぜ〰ごあぉぜ〴〩਼㰠⽓ 䝯呯 䐠⡳畢獥捴楯渮㌮㘩‾㸊⡜㌷㙜㌷㝜〰ぃぬどのどっちぬぜ〴ぜ〰こぴふつどづびぜ〴ぜ〰はてぜ〴ぜ〰ぇがぉぜ〴ぜ〰どのぜ〴ぜ〰ごあぉぜ〴〩਼㰠⽓ 䝯呯 䐠⡳散瑩潮⸴ Item: Title: ぉねばちっぴぜ〴ぜ〰はてぜ〴ぜ〰ぇづのづぴどっぜ〴ぜ〰ざちひどちぴどはのぜ〴ぜ〰どのぜ〴ぜ〰ぁあぃぃ〸ぜ〴ぜ〰ぜ〵ぜ〰ぅのっはつどのでぜ〴ぜ〰こさげ〱ぜ〵ㅜ〰ぜ〴ぜ〰ちのつぜ〴ぜ〰ごげぐき〴ぜ〴ぜ〰どのぜ〴ぜ〰ごあぉぜ〴〩਼㰠⽓ 䝯呯 䐠⡳畢獥捴楯渮㌮㔩‾㸊⡜㌷㙜㌷㝜〰ぐひづっぬどのどっちぬぜ〴ぜ〰こぴふつどづびぜ〴ぜ〰はてぜ〴ぜ〰こさげ〱ぜ〴ぜ〰ぉのとどぢどぴどはのぜ〴ぜ〰どのぜ〴ぜ〰ごあぉぜ〴〩਼㰠⽓ 䝯呯 䐠⡳畢獥捴楯渮㌮㘩‾㸊⡜㌷㙜㌷㝜〰ぃぬどのどっちぬぜ〴ぜ〰こぴふつどづびぜ〴ぜ〰はてぜ〴ぜ〰ぇがぉぜ〴ぜ〰どのぜ〴ぜ〰ごあぉぜ〴〩਼㰠⽓ 䝯呯 䐠⡳散瑩潮⸴ Item: Title: ぐひづっぬどのどっちぬぜ〴ぜ〰こぴふつどづびぜ〴ぜ〰はてぜ〴ぜ〰こさげ〱ぜ〴ぜ〰ぉのとどぢどぴどはのぜ〴ぜ〰どのぜ〴ぜ〰ごあぉぜ〴〩਼㰠⽓ 䝯呯 䐠⡳畢獥捴楯渮㌮㘩‾㸊⡜㌷㙜㌷㝜〰ぃぬどのどっちぬぜ〴ぜ〰こぴふつどづびぜ〴ぜ〰はてぜ〴ぜ〰ぇがぉぜ〴ぜ〰どのぜ〴ぜ〰ごあぉぜ〴〩਼㰠⽓ 䝯呯 䐠⡳散瑩潮⸴ Item: Title: ぃぬどのどっちぬぜ〴ぜ〰こぴふつどづびぜ〴ぜ〰はてぜ〴ぜ〰ぇがぉぜ〴ぜ〰どのぜ〴ぜ〰ごあぉぜ〴〩਼㰠⽓ 䝯呯 䐠⡳散瑩潮⸴ Item: Title: ぃはのっぬふびどはのびぜ〴〩਼㰠⽓ 䝯呯 䐠⡳散瑩潮⸴ Item: Title: げづてづひづのっづび Filters: FilterPipeline: FlateDecode Fonts: Type1: Font: BaseFont: LXDRAY+Rpxmi FontSubset: true FirstChar: 34 LastChar: 34 FontDescriptor: FontName: LXDRAY+Rpxmi Flags: Symbolic FontBBox: -70, -289, 949, 802 FontFile: true Font: BaseFont: NSAREJ+URWPalladioL-Ital FontSubset: true FirstChar: 3 LastChar: 151 FontDescriptor: FontName: NSAREJ+URWPalladioL-Ital Flags: Symbolic FontBBox: -170, -305, 1010, 941 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