The implementation of transcranial Doppler ultrasonography for preclinical study of migraine

Transcranial Doppler ultrasonography is used to study intracranial blood flow changes associated with migraine in humans, but whether this method is helpful in preclinical settings is yet unknown. To identify changes in rat intracranial blood flow specific to trigeminovascular activation??????a key process in migraine pathophysiology??????we measured Doppler indices in the middle cerebral artery and basilar artery before, during, and after dural or somatosensory electrical stimulation. Hemodynamic changes specific to dural stimulation were tested further in separate experiments. After baseline recordings, the animals received cumulative infusions of valproate (100 mg/kg, trice), sumatriptan (0.3, 1, and 3 mg/kg), or saline, and dural stimulation with measurement of Doppler indices was repeated every 10 min for 1 h. Several parameters of blood flow in the rat middle cerebral artery underwent alterations specific to trigeminovascular activation. These changes, however, were insensitive to valproate and sumatriptan and diminished over time. These findings question the reliability of blood flow velocity variations in large intracranial vessels as biological markers of migraine-related processes and do not support the idea of using transcranial Doppler ultrasonography for preclinical screening of antimigraine treatments, at least in the model of acute trigeminovascular activation in rats.