title: Modulatory role of cyclooxygenase-2 in cerebrovascular coupling.
abstract: To investigate the role of cyclooxygenase-2 (COX-2) in the cerebrovascular coupling, hemodynamic and neuronal responses to forepaw stimulation were measured in alpha-chloralose-anesthetized rats (N = 18) before and after intravenous administration of Meloxicam (MEL), a preferential COX-2 inhibitor, and following a bolus of prostaglandin E(2) (PGE(2)), a prominent vasodilatatory product of COX-2 catalyzed metabolism of arachidonic acid. The cerebral blood flow (CBF) and blood-oxygenation-level-dependent (BOLD) response was quantified using continuous arterial spin labeling magnetic resonance imaging. Neuronal activity was measured by recording somatosensory-evoked potentials (SEPs) via intracranial electrodes. Both MEL and PGE(2) had a significant effect on the activation-elicited CBF (P < 10(-6)) and BOLD (P < 10(-6)) responses, without affecting the baseline perfusion. Meloxicam decreased brain COX enzymatic activity by 57 +/- 14% and decreased the stimulation-induced CBF response to 32 +/- 2% and BOLD to 46 +/- 1% of their respective pre-drug amplitudes. In turn, PGE(2) bolus resulted in a partial recovery of functional hyperemia, with the CBF response recovering to 52 +/- 3% and the BOLD response to 56 +/- 2% of their values prior to MEL administration. There was no concomitant decrease in either amplitudes or latencies of SEP components. These findings suggest a modulatory role of COX-2 products in the cerebrovascular coupling and provide evidence for existence of a functional metabolic buffer.
authors.affiliation: Cerebral Microcirculation Unit, Laboratory of Functional and Molecular Imaging, National Institute of Neurological Disorders and Stroke/NIH, 10 Center Drive, Building 10, Room B1D109, Bethesda, MD 20892-1065, USA. stefanovicb@ninds.nih.gov
authors.forename: Bojana
authors.initials: B
authors.lastname: Stefanovic
authors.forename: Francesca
authors.initials: F
authors.lastname: Bosetti
authors.forename: Afonso C
authors.initials: AC
authors.lastname: Silva
mesh_terms: D000818:Animals; D001783:Blood Flow Velocity; D002560:Cerebrovascular Circulation / Q000187:drug effects / Q000502:physiology*; D051546:Cyclooxygenase 2 / Q000378:metabolism*; D016861:Cyclooxygenase Inhibitors / Q000494:pharmacology*; D015232:Dinoprostone / Q000494:pharmacology; D004558:Electric Stimulation; D005552:Forelimb / Q000294:innervation; D008279:Magnetic Resonance Imaging; D008297:Male; D000077239:Meloxicam; D010100:Oxygen / Q000097:blood; D051381:Rats; D017207:Rats, Sprague-Dawley; D013843:Thiazines / Q000494:pharmacology*; D013844:Thiazoles / Q000494:pharmacology*
chemical_list: D016861:Cyclooxygenase Inhibitors; D013843:Thiazines; D013844:Thiazoles; D051546:Cyclooxygenase 2; D015232:Dinoprostone; D010100:Oxygen; D000077239:Meloxicam