2016
DOI: 10.1161/jaha.116.003465
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Glibenclamide Is Comparable to Target Temperature Management in Improving Survival and Neurological Outcome After Asphyxial Cardiac Arrest in Rats

Abstract: BackgroundWe previously have shown that glibenclamide (GBC), a sulfonylurea receptor 1–transient receptor potential M4 (SUR1‐TRPM4) channel inhibitor, improves survival and neurological outcome after asphyxial cardiac arrest and cardiopulmonary resuscitation (ACA/CPR). Here, we further compare the efficacy of GBC with target temperature management (TTM) and determine whether the efficacy of GBC is affected by TTM.Methods and ResultsMale Sprague‐Dawley rats (n=213) subjected to 10‐minute ACA/CPR were randomized… Show more

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Cited by 36 publications
(33 citation statements)
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“…Brain tissues underwent lysis and were used for immunoblotting, as previously reported 36. Antibodies against Phospho‐AMPK (p‐AMPK;1:1000; Cell Signaling Technology, Beverly, MA), AMPK (1:1000; Cell Signaling Technology), LC3 (1:1000; Abcam), p62 (1:1000; Abcam), and mouse anti–β‐actin (1:10 000; CWBIO, Beijing, China) were used.…”
Section: Methodsmentioning
confidence: 99%
“…Brain tissues underwent lysis and were used for immunoblotting, as previously reported 36. Antibodies against Phospho‐AMPK (p‐AMPK;1:1000; Cell Signaling Technology, Beverly, MA), AMPK (1:1000; Cell Signaling Technology), LC3 (1:1000; Abcam), p62 (1:1000; Abcam), and mouse anti–β‐actin (1:10 000; CWBIO, Beijing, China) were used.…”
Section: Methodsmentioning
confidence: 99%
“…Unlike many other constitutively expressed SUR1 regulated channels in various systemic tissues, SUR1-TRPM4 is unique in that it is not normally present in the CNS, but undergoes de novo upregulation after CNS injury [36]. Upregulation of SUR1 with or without TRPM4 (hereafter SUR1±TRPM4) has been demonstrated in multiple CNS cell types (neurons, astrocytes, endothelial cells, macrophages, microglia) and models of injury, including ischemic stroke [56][57][58][59], TBI [50,[60][61][62], spinal cord injury (SCI) [63,64], intracerebral hemorrhage (ICH) [65], subarachnoid hemorrhage (SAH) [66,67], CNS metastases [68], cardiac arrest [69,70], hepatic failure [71], and encephalomyelitis [72][73][74] ( Figure 1A). The increased expression in several cell-types of the neurovascular unit renders SUR1-TRPM4 a likely contributor across the spectrum of cerebral edema endotypes (reviewed elsewhere [14,15,75]), including cellular/cytotoxic edema, ionic edema, vasogenic edema, and eventually hemorrhagic transformation/progression with complete disintegration of the BBB and oncotic death of endothelial cells ( Figure 1C) [14,15,76].…”
Section: Sur1-trpm4 Gli and Cerebral Edemamentioning
confidence: 99%
“…Given its de novo upregulation, SUR1-TRPM4 inhibition has the potential to prevent or limit cerebral edema generation and hemorrhage progression at early stages of injury, with minimal side-effects. Channel blockade by gene silencing, deletion, or pharmacologic agents (primarily GLI) has demonstrated benefit in the aforementioned models of CNS injury [46,56,57,60,61,[64][65][66][67][68][69][70]72,73,[77][78][79][80][81][82][83][84][85][86][87][88]. GLI, also known as glyburide, inhibits SUR1-TRPM4 at nanomolar concentrations (EC 50 = 48 nM) by increasing the probability of the channel's long closed state (frequency and duration), not by affecting channel conductance [53].…”
Section: Sur1-trpm4 Gli and Cerebral Edemamentioning
confidence: 99%
“…It is pertinent to note that in addition to inhibition of K ATP channels, glibenclamide has additional modes of action. 38,39 In this study, glibenclamide blocked the increase in outflow facility induced by both l-cysteine and NaHS without affecting baseline flow. Indeed, glibenclamide has also been shown to antagonize the pharmacological actions of H 2 S-releasing compounds in several biological systems.…”
Section: Discussionmentioning
confidence: 53%