RGD Reference Report - Cyclooxygenase-2-Derived Prostaglandins Mediate Cerebral Microcirculation in a Juvenile Ischemic Rat Model. - Rat Genome Database

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Cyclooxygenase-2-Derived Prostaglandins Mediate Cerebral Microcirculation in a Juvenile Ischemic Rat Model.

Authors: Leger, Pierre-Louis  Pansiot, Julien  Besson, Valerie  Palmier, Bruno  Renolleau, Sylvain  Baud, Olivier  Cauli, Bruno  Charriaut-Marlangue, Christiane 
Citation: Leger PL, etal., Stroke. 2016 Dec;47(12):3048-3052. doi: 10.1161/STROKEAHA.116.015095. Epub 2016 Nov 10.
RGD ID: 401960086
Pubmed: PMID:27834752   (View Abstract at PubMed)
DOI: DOI:10.1161/STROKEAHA.116.015095   (Journal Full-text)


BACKGROUND AND PURPOSE: We previously showed that the selective neuronal nitric oxide synthase inhibitor 7-nitroindazole (7-NI) increases cerebral microcirculation in a juvenile ischemic rat model. We address the roles of cyclooxygenase (COX)-elaborated prostaglandins in collateral recruitment and blood supply.
METHODS: Fourteen-day-old rats were subjected to ischemia-reperfusion and treated with either PBS or 7-NI (25 mg/kg) at the reperfusion onset. Six-keto-prostaglandin F1α was measured using ELISA. COX-1 and COX-2 and prostaglandin terminal synthesizing enzymes were evaluated using reverse-transcriptase polymerase chain reaction and immunofluorescence. Microvascular blood flow indexes (artery diameter and capillaries number) were measured using sidestream dark-field videomicroscopy in PBS- and 7-NI-treated ischemic rats in the absence or presence of the COX-2 inhibitor NS-398 (5 mg/kg). Cell death was measured with the TUNEL (terminal transferase dUTP nick end labeling) assay and cleaved-caspase-3 immunostaining.
RESULTS: Six-keto-prostaglandin F1α and COX-2, associated with a prostaglandin E synthase, were significantly increased in PBS- and 7-NI-treated animals 15 minutes and 1 hour after ischemia-reperfusion, respectively. In contrast and as compared with PBS, 7-NI significantly decreased prostacyclin synthase and cytosolic prostaglandins E synthase mRNA. Selective COX-2 inhibition significantly decreased blood flow indexes and significantly reversed the effects of 7-NI, including the number of TUNEL+- and cleaved-caspase-3+-nuclei.
CONCLUSIONS: These results show that the juvenile rat brains mostly respond to ischemia by a COX-2-dependent prostaglandins production and suggest that the transcriptional responses observed under 7-NI facilitate and reorient COX-2-dependent prostaglandins production.



RGD Manual Disease Annotations    Click to see Annotation Detail View

  
Object SymbolSpeciesTermQualifierEvidenceWithNotesSourceOriginal Reference(s)
PTGISHumantransient cerebral ischemia treatmentISOPtgis (Rattus norvegicus) RGD 
PtgisRattransient cerebral ischemia treatmentIMP  RGD 
PtgisMousetransient cerebral ischemia treatmentISOPtgis (Rattus norvegicus) RGD 

Gene-Chemical Interaction Annotations    Click to see Annotation Detail View

  
Object SymbolSpeciesTermQualifierEvidenceWithNotesSourceOriginal Reference(s)
PTGISHuman7-NITROINDAZOLE  ISOPtgis (Rattus norvegicus)7-nitroindazole decreases Ptgis mRNA in cerebral cortexRGD 
PtgisRat7-NITROINDAZOLE  EXP 7-nitroindazole decreases Ptgis mRNA in cerebral cortexRGD 
PtgisMouse7-NITROINDAZOLE  ISOPtgis (Rattus norvegicus)7-nitroindazole decreases Ptgis mRNA in cerebral cortexRGD 

Objects Annotated

Genes (Rattus norvegicus)
Ptgis  (prostaglandin I2 synthase)

Genes (Mus musculus)
Ptgis  (prostaglandin I2 (prostacyclin) synthase)

Genes (Homo sapiens)
PTGIS  (prostaglandin I2 synthase)


Additional Information