Cyclooxygenase-2 contributes to functional hyperemia in whisker-barrel cortex.
The prostanoid-synthesizing enzyme cyclooxygenase-2 (COX-2) is expressed in selected cerebral cortical neurons and is involved in synaptic signaling. We sought to determine whether COX-2 participates in the increase in cerebral blood flow produced by synaptic activity in the somatosensory cortex. In anesthetized mice, the vibrissae were stimulated mechanically, and cerebral blood flow was recorded in the contralateral somatosensory cortex by a laser-Doppler probe. We found that the COX-2 inhibitor NS-398 attenuates the increase in somatosensory cortex blood flow produced by vibrissal stimulation. Furthermore, the flow response was impaired in mice lacking the COX-2 gene, whereas the associated increase in whisker-barrel cortex glucose use was not affected. The increases in cerebral blood flow produced by hypercapnia, acetylcholine, or bradykinin were not attenuated by NS-398, nor did they differ between wild-type and COX-2 null mice. The findings provide evidence for a previously unrecognized role of COX-2 in the mechanisms coupling synaptic activity to neocortical blood flow and provide an insight into one of the functions of constitutive COX-2 in the CNS.
Niwa
K
K
Center for Clinical and Molecular Neurobiology, Departments of Neurology and Neuroscience, University of Minnesota Medical School, Minneapolis, Minnesota 55455, USA.
Araki
E
E
Morham
S G
SG
Ross
M E
ME
Iadecola
C
C
D000109:Acetylcholine / Q000494:pharmacology; D000818:Animals; D001794:Blood Pressure / Q000187:drug effects; D001920:Bradykinin / Q000494:pharmacology; D001921:Brain / Q000187:drug effects / Q000502:physiology*; D002245:Carbon Dioxide / Q000097:blood; D002560:Cerebrovascular Circulation / Q000187:drug effects / Q000502:physiology*; D051546:Cyclooxygenase 2; D052246:Cyclooxygenase 2 Inhibitors; D016861:Cyclooxygenase Inhibitors / Q000494:pharmacology*; D007839:Functional Laterality; D005947:Glucose / Q000378:metabolism; D006940:Hyperemia; D007527:Isoenzymes / Q000172:deficiency / Q000235:genetics / Q000378:metabolism*; D051379:Mice; D008810:Mice, Inbred C57BL; D018345:Mice, Knockout; D009578:Nitrobenzenes / Q000494:pharmacology*; D009928:Organ Specificity; D010100:Oxygen / Q000097:blood; D010812:Physical Stimulation; D011451:Prostaglandin-Endoperoxide Synthases / Q000172:deficiency / Q000235:genetics / Q000378:metabolism*; D012039:Regional Blood Flow / Q000187:drug effects; D013003:Somatosensory Cortex / Q000098:blood supply / Q000502:physiology*; D013449:Sulfonamides / Q000494:pharmacology*; D013569:Synapses / Q000502:physiology; D014738:Vibrissae / Q000294:innervation*
D052246:Cyclooxygenase 2 Inhibitors; D016861:Cyclooxygenase Inhibitors; D007527:Isoenzymes; D009578:Nitrobenzenes; D013449:Sulfonamides; C080955:N-(2-cyclohexyloxy-4-nitrophenyl)methanesulfonamide; D002245:Carbon Dioxide; D051546:Cyclooxygenase 2; D011451:Prostaglandin-Endoperoxide Synthases; D005947:Glucose; D000109:Acetylcholine; D010100:Oxygen; D001920:Bradykinin