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 cerebr al blood flow produced by synaptic activity in the somatosensory cortex. In anesthetized mice, the vibrissae were stimulated mechanically, and cerebra l blood flow was recorded in the contralateral somatosensory cortex by a la ser-Doppler probe. We found that the COX-2 inhibitor NS-398 attenuates the increase in somatosensory cortex blood flow produced by vibrissal stimulati on. Furthermore, the flow response was impaired in mice lacking the COX-2 g ene, whereas the associated increase in whisker-barrel cortex glucose use w as not affected. The increases in cerebral blood flow produced by hypercapn ia, acetylcholine, or bradykinin were not attenuated by NS-398, nor did the y differ between wild-type and COX-2 null mice. The findings provide eviden ce for a previously unrecognized role of COX-2 in the mechanisms coupling s ynaptic activity to neocortical blood flow and provide an insight into one of the functions of constitutive COX-2 in the CNS.