title: Contribution of prostanoid signaling to the evolution of spreading depolarization and the associated cerebral blood flow response.
abstract: The significance of prostanoid signaling in neurovascular coupling during somatosensory stimulation is increasingly more appreciated, yet its involvement in mediating the cerebral blood flow (CBF) response to spreading depolarization (SD) has remained inconclusive. Selective cyclooxygenase (COX) enzyme inhibitors (NS-398, SC-560) or an antagonist (L161,982) of the EP4 type prostaglandin E2 receptor were applied topically to a cranial window over the parietal cortex of isoflurane-anesthetized Sprague-Dawley rats (n = 60). Global forebrain ischemia was induced by occlusion of both common carotid arteries in half of the animals. SDs were triggered by the topical application of 1M KCl. SD occurrence was confirmed by the acquisition of DC potential, and CBF variations were recorded by laser-Doppler flowmetry. EP4 receptor antagonism significantly decreased peak hyperemia and augmented post-SD oligemia in the intact but not in the ischemic cortex. COX-1 inhibition and EP4 receptor blockade markedly delayed repolarization after SD in the ischemic but not in the intact brain. COX-2 inhibition achieved no significant effect on any of the end points taken. The data suggest, that activation of EP4 receptors initiates vasodilation in response to SD in the intact brain, and - together with COX-1 derived prostanoids - shortens SD duration in the acute phase of ischemia.
authors: Department of Medical Physics and Informatics, Faculty of Medicine &Faculty of Science and Informatics, University of Szeged, H-6720 Szeged, Korányi fasor 9, Hungary.
authors: Dániel Péter
authors: DP
authors: Varga
authors: Department of Medical Physics and Informatics, Faculty of Medicine &Faculty of Science and Informatics, University of Szeged, H-6720 Szeged, Korányi fasor 9, Hungary.
authors: Tamás
authors: T
authors: Puskás
authors: Department of Medical Physics and Informatics, Faculty of Medicine &Faculty of Science and Informatics, University of Szeged, H-6720 Szeged, Korányi fasor 9, Hungary.
authors: Ákos
authors: Á
authors: Menyhárt
authors: Department of Medical Physics and Informatics, Faculty of Medicine &Faculty of Science and Informatics, University of Szeged, H-6720 Szeged, Korányi fasor 9, Hungary.
authors: Péter
authors: P
authors: Hertelendy
authors: Department of Medical Physics and Informatics, Faculty of Medicine &Faculty of Science and Informatics, University of Szeged, H-6720 Szeged, Korányi fasor 9, Hungary.
authors: Dániel
authors: D
authors: Zölei-Szénási
authors: Department of Medical Physics and Informatics, Faculty of Medicine &Faculty of Science and Informatics, University of Szeged, H-6720 Szeged, Korányi fasor 9, Hungary.
authors: Réka
authors: R
authors: Tóth
authors: Department of Medical Physics and Informatics, Faculty of Medicine &Faculty of Science and Informatics, University of Szeged, H-6720 Szeged, Korányi fasor 9, Hungary.
authors: Orsolya
authors: O
authors: Ivánkovits-Kiss
authors: Department of Medical Physics and Informatics, Faculty of Medicine &Faculty of Science and Informatics, University of Szeged, H-6720 Szeged, Korányi fasor 9, Hungary.
authors: Ferenc
authors: F
authors: Bari
authors: Department of Medical Physics and Informatics, Faculty of Medicine &Faculty of Science and Informatics, University of Szeged, H-6720 Szeged, Korányi fasor 9, Hungary.
authors: Eszter
authors: E
authors: Farkas
mesh_terms: D000818:Animals; D001921:Brain / Q000503:physiopathology; D002545:Brain Ischemia / Q000503:physiopathology; D002560:Cerebrovascular Circulation / Q000187:drug effects / Q000502:physiology*; D016861:Cyclooxygenase Inhibitors / Q000494:pharmacology; D017078:Laser-Doppler Flowmetry; D008297:Male; D009578:Nitrobenzenes / Q000494:pharmacology; D016548:Prosencephalon / Q000187:drug effects / Q000473:pathology; D011453:Prostaglandins / Q000378:metabolism*; D011720:Pyrazoles / Q000494:pharmacology; D051381:Rats; D017207:Rats, Sprague-Dawley; D015398:Signal Transduction; D013449:Sulfonamides / Q000494:pharmacology; D013876:Thiophenes / Q000494:pharmacology; D014230:Triazoles / Q000494:pharmacology
chemical_list: D016861:Cyclooxygenase Inhibitors; C508711:L-161982; D009578:Nitrobenzenes; D011453:Prostaglandins; D011720:Pyrazoles; C115461:SC 560; D013449:Sulfonamides; D013876:Thiophenes; D014230:Triazoles; C080955:N-(2-cyclohexyloxy-4-nitrophenyl)methanesulfonamide