Modulation of cerebral blood oxygenation by indomethacin: MRI at rest and functional brain activation

The modulation of blood oxygenation level-dependent (BOLD) cerebral MRI contrast by the vasoconstrictive drug indomethacin (i.v. 0.2 mg/kg b.w.) was investigated in 10 healthy young adults without and with functional challenge (repetitive and sustained visual activation). For comparison, isotonic saline (placebo, 20 mL) and acetylsalicylate (i.v. 500 mg) were investigated as well, each in separate sessions using identical protocols. After indomethacin, dynamic T2*-weighted echo-planar MRI at 2.0 T revealed a rapid decrease in MRI signal intensity by 2.1%-2.6% in different gray matter regions (P < or = 0.001 compared to placebo), which was not observed for acetylsalicylate and the placebo condition. Regional signal differences were not significant within gray matter, but all gray matter regions differed significantly from the signal decrease of only 1.2% +/- 0.7% observed in white matter (P = 0.001). For the experimental parameters used, a 1% MRI signal decrease in response to indomethacin was estimated to correlate with a decrease of the cerebral blood flow by about 12 ml/100 g/minute, and an increase of the oxygen extraction fraction by about 15%. Responses to visual activation were not affected by saline or acetylsalicylate, and yielded 5.0%-5.5% BOLD MRI signal increases both before and after drug application. In contrast, indomethacin reduced the initial response strength to 82%-85% of that obtained without the drug. The steady-state response during sustained activation reached only 47% of the corresponding pre-drug level (P < 0.01). During repetitive activation the BOLD contrast was reduced to 66% of that observed for control conditions (P < 0.001). In conclusion, indomethacin attenuates the vasodilatory force at functional brain activation, indicating different mechanisms governing neurovascular coupling.