Effect of non-steroid anti-inflammatory drugs on neurovascular coupling in humans

Neuronal activation induced cerebral blood flow increase was shown in animal experiments to require the presence of functioning cyclooxygenase. Our aim was to study whether widely used, non-steroid anti-inflammatory drugs (NSAIDs), given orally in usual therapeutic doses, inhibit neurovascular coupling in humans.

By using a visual cortex stimulation paradigm, the flow velocity response was measured by transcranial Doppler sonography in both posterior cerebral arteries of fifteen young healthy adults. The investigation was repeated in the same subjects after 2-day administration of 3×25 mg indomethacin (indomethacin phase) and 2×550 mg naproxen (naproxen phase). Visual-evoked-potentials were also recorded during the control phase and after administration of NSAIDs.

Basal flow velocity significantly decreased while the pulsatility index increased after administration of either indomethacin or naproxen (p<0.01). Despite unchanged visual-evoked-potentials, the visually evoked flow velocity increase (26±7% in the control phase) significantly declined after administration of indomethacin (19±5%; p<0.01) or naproxen (20±5%; p<0.02).

Oral administration of indomethacin or naproxen in their usual therapeutic doses significantly impaired the resting and the visually evoked blood flow regulations in healthy human subjects. Together with stable evoked potentials, our findings indicate disturbance of neurovascular coupling.