Neuroprotective effect of sumatriptan, a 5-HT(1D) receptor agonist, in focal cerebral ischemia of rat brain.
The effect of the 5-HT(1D) receptor agonist sumatriptan on the volume of ischemic injury was studied in rats subjected to permanent middle cerebral artery (MCA) occlusion. Sumatriptan (2 mg/kg) was administered intravenously 5 minutes after MCA occlusion and the ischemic injury volume was determined 3 hours after MCA occlusion using regional adenosine-5'-triphosphate imaging. In addition, electroencephalographic activity, direct current (DC) potential and cortical blood flow (CBF) was monitored throughout the experiment. In untreated animals, MCA occlusion resulted in a decline in penumbral CBF to 43.3%+/-7.6% of control, 21 spreading depression (SD)-like DC shifts with an average integrated depolarization negativity of 320.2+/-297.4 (mVxmin) and an ATP depletion volume of 61.8+/-22.9 mm(3) (mean+/-SD). Three hours after MCA occlusion in sumatriptan-treated animals, penumbral CBF recovered to 63.5%+/-12.6% of control (P<.05), only 13 SD-like shifts were detected (P<.05) with a significantly reduced integrated depolarization negativity of 104.7+/-98.4 (mVxmin) (P<.05), and the volume of ATP depletion decreased to 16.6+/-12.3 mm(3) (P<.01). However, no significant neuroprotective effect was observed for the caudate nucleus (untreated, 19.7+/-16.5 mm(3); treated, 7.9+/-8.5 mm(3)). The reduction in the volume of ischemic injury in sumatriptantreated animals is explained by both the improvement of blood flow and the inhibition of SD-like shifts leading to an amelioration of the misrelationship between the depolarization-related energy demand and flow-dependent substrate delivery.
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Max-Planck-Institute for Neurological Research, Department of Experimental Neurology, Gleueler Strasse 50, Lindenthal, Germany.