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Neuroprotective effect of sumatriptan, a 5-HT 1D receptor agonist, in focal cerebral ischemia of rat brain

Journal of Stroke and Cerebrovascular Diseases, ISSN: 1052-3057, Vol: 7, Issue: 4, Page: 242-249
1998
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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 spreadsing depression (SD)-like DC shifts with an average integrated depolarization negativity of 320.2±297.4 (mV×min) 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 (mV×min) ( 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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