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Citations to this article

Endothelial sulfonylurea receptor 1–regulated NCCa-ATP channels mediate progressive hemorrhagic necrosis following spinal cord injury
J. Marc Simard, … , S. Kyoon Woo, Volodymyr Gerzanich
J. Marc Simard, … , S. Kyoon Woo, Volodymyr Gerzanich
Published August 1, 2007
Citation Information: J Clin Invest. 2007;117(8):2105-2113. https://doi.org/10.1172/JCI32041.
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Research Article Neuroscience Article has an altmetric score of 7

Endothelial sulfonylurea receptor 1–regulated NCCa-ATP channels mediate progressive hemorrhagic necrosis following spinal cord injury

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Abstract

Acute spinal cord injury (SCI) causes progressive hemorrhagic necrosis (PHN), a poorly understood pathological process characterized by hemorrhage and necrosis that leads to devastating loss of spinal cord tissue, cystic cavitation of the cord, and debilitating neurological dysfunction. Using a rodent model of severe cervical SCI, we tested the hypothesis that sulfonylurea receptor 1–regulated (SUR1-regulated) Ca2+-activated, [ATP]i-sensitive nonspecific cation (NCCa-ATP) channels are involved in PHN. In control rats, SCI caused a progressively expansive lesion with fragmentation of capillaries, hemorrhage that doubled in volume over 12 hours, tissue necrosis, and severe neurological dysfunction. SUR1 expression was upregulated in capillaries and neurons surrounding necrotic lesions. Patch clamp of cultured endothelial cells exposed to hypoxia showed that upregulation of SUR1 was associated with expression of functional SUR1-regulated NCCa-ATP channels. Following SCI, block of SUR1 by glibenclamide or repaglinide or suppression of Abcc8, which encodes for SUR1 by phosphorothioated antisense oligodeoxynucleotide essentially eliminated capillary fragmentation and progressive accumulation of blood, was associated with significant sparing of white matter tracts and a 3-fold reduction in lesion volume, and resulted in marked neurobehavioral functional improvement compared with controls. We conclude that SUR1-regulated NCCa-ATP channels in capillary endothelium are critical to development of PHN and constitute a major target for therapy in SCI.

Authors

J. Marc Simard, Orest Tsymbalyuk, Alexander Ivanov, Svetlana Ivanova, Sergei Bhatta, Zhihua Geng, S. Kyoon Woo, Volodymyr Gerzanich

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Total citations by year

Year: 2024 2023 2022 2021 2020 2019 2018 2017 2016 2015 2014 2013 2012 2011 2010 2009 2008 2007 Total
Citations: 4 8 7 6 9 7 8 2 6 5 6 10 6 9 4 6 2 1 106
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Citations to this article in year 2013 (10)

Title and authors Publication Year
TRPM4 inhibition promotes angiogenesis after ischemic stroke
KP Loh, G Ng, CY Yu, CK Fhu, D Yu, R Vennekens, B Nilius, TW Soong, P Liao
Pflügers Archiv : European journal of physiology 2013
Immortalized human cerebral microvascular endothelial cells maintain the properties of primary cells in an in vitro model of immune migration across the blood brain barrier
BP Daniels, L Cruz-Orengo, TJ Pasieka, PO Couraud, IA Romero, B Weksler, JA Cooper, TL Doering, RS Klein
Journal of Neuroscience Methods 2013
Systemic iron chelation results in limited functional and histological recovery after traumatic spinal cord injury in rats
A Sauerbeck, DL Schonberg, JL Laws, DM McTigue
Experimental Neurology 2013
Intravenous Infusion of Magnesium Chloride Improves Epicenter Blood Flow during the Acute Stage of Contusive Spinal Cord Injury in Rats
JM Muradov, T Hagg
Journal of Neurotrauma 2013
MRI evidence that glibenclamide reduces acute lesion expansion in a rat model of spinal cord injury
JM Simard, PG Popovich, O Tsymbalyuk, J Caridi, RP Gullapalli, MJ Kilbourne, V Gerzanich
Spinal Cord 2013
Disruption of Ion Homeostasis in the Neurogliovascular Unit Underlies the Pathogenesis of Ischemic Cerebral Edema
A Khanna, KT Kahle, BP Walcott, V Gerzanich, JM Simard
Translational Stroke Research 2013
The Sur1-Trpm4 Channel in Spinal Cord Injury
JM Simard, SK Woo, B Aarabi, V Gerzanich
Journal of Spine 2013
Glibenclamide for the treatment of acute CNS injury
DB Kurland, C Tosun, A Pampori, JK Karimy, NM Caffes, V Gerzanich, JM Simard
Pharmaceuticals (Basel, Switzerland) 2013
Derivation of multivariate syndromic outcome metrics for consistent testing across multiple models of cervical spinal cord injury in rats
AR Ferguson, KA Irvine, JC Gensel, JL Nielson, A Lin, J Ly, MR Segal, RR Ratan, JC Bresnahan, MS Beattie
PloS one 2013
Inhibition of SUR1 decreases the vascular permeability of cerebral metastases.
Thompson EM, Pishko GL, Muldoon LL, Neuwelt EA
Neoplasia (New York, N.Y.) 2013

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