RGD Reference Report - Glibenclamide reduces inflammation, vasogenic edema, and caspase-3 activation after subarachnoid hemorrhage. - Rat Genome Database

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Glibenclamide reduces inflammation, vasogenic edema, and caspase-3 activation after subarachnoid hemorrhage.

Authors: Simard, JM  Geng, Z  Woo, SK  Ivanova, S  Tosun, C  Melnichenko, L  Gerzanich, V 
Citation: Simard JM, etal., J Cereb Blood Flow Metab. 2009 Feb;29(2):317-30. Epub 2008 Oct 15.
RGD ID: 2325137
Pubmed: PMID:18854840   (View Abstract at PubMed)
PMCID: PMC2740919   (View Article at PubMed Central)
DOI: DOI:10.1038/jcbfm.2008.120   (Journal Full-text)

Subarachnoid hemorrhage (SAH) causes secondary brain injury due to vasospasm and inflammation. Here, we studied a rat model of mild-to-moderate SAH intended to minimize ischemia/hypoxia to examine the role of sulfonylurea receptor 1 (SUR1) in the inflammatory response induced by SAH. mRNA for Abcc8, which encodes SUR1, and SUR1 protein were abundantly upregulated in cortex adjacent to SAH, where tumor-necrosis factor-alpha (TNFalpha) and nuclear factor (NF)kappaB signaling were prominent. In vitro experiments confirmed that Abcc8 transcription is stimulated by TNFalpha. To investigate the functional consequences of SUR1 expression after SAH, we studied the effect of the potent, selective SUR1 inhibitor, glibenclamide. We examined barrier permeability (immunoglobulin G, IgG extravasation), and its correlate, the localization of the tight junction protein, zona occludens 1 (ZO-1). SAH caused a large increase in barrier permeability and disrupted the normal junctional localization of ZO-1, with glibenclamide significantly reducing both effects. In addition, SAH caused large increases in markers of inflammation, including TNFalpha and NFkappaB, and markers of cell injury or cell death, including IgG endocytosis and caspase-3 activation, with glibenclamide significantly reducing these effects. We conclude that block of SUR1 by glibenclamide may ameliorate several pathologic effects associated with inflammation that lead to cortical dysfunction after SAH.



RGD Manual Disease Annotations    Click to see Annotation Detail View
Object SymbolSpeciesTermQualifierEvidenceWithNotesSourceOriginal Reference(s)
TJP1HumanSubarachnoid Hemorrhage  ISOTjp1 (Rattus norvegicus)protein:altered localizationRGD 
Tjp1RatSubarachnoid Hemorrhage  IDA protein:altered localizationRGD 
Tjp1MouseSubarachnoid Hemorrhage  ISOTjp1 (Rattus norvegicus)protein:altered localizationRGD 
ABCC8HumanTraumatic Subarachnoid Hemorrhage treatmentISOAbcc8 (Rattus norvegicus) RGD 
Abcc8RatTraumatic Subarachnoid Hemorrhage treatmentIMP  RGD 
Abcc8MouseTraumatic Subarachnoid Hemorrhage treatmentISOAbcc8 (Rattus norvegicus) RGD 

Gene Ontology Annotations    Click to see Annotation Detail View

Biological Process
Object SymbolSpeciesTermQualifierEvidenceWithNotesSourceOriginal Reference(s)
Abcc8Ratnegative regulation of blood-brain barrier permeability  IMP  RGD 
Abcc8Ratpositive regulation of tumor necrosis factor production  IMP  RGD 

Objects Annotated

Genes (Rattus norvegicus)
Abcc8  (ATP binding cassette subfamily C member 8)
Tjp1  (tight junction protein 1)

Genes (Mus musculus)
Abcc8  (ATP-binding cassette, sub-family C member 8)
Tjp1  (tight junction protein 1)

Genes (Homo sapiens)
ABCC8  (ATP binding cassette subfamily C member 8)
TJP1  (tight junction protein 1)


Additional Information