Treatment with an i.v. calcium overload blocker (flunarizine) in acute stroke

Hülser, P.-J.; Bernhart, H.; Marbach, C.; Kornhuber, H. H.

doi:10.1007/bf00450543

Cited by 9 publications

(1 citation statement)

References 19 publications

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“…The intravenous dose of flunarizine corresponds to the high-dose treatment in a clinical pilot study of acute stroke. 28 The oral dose was derived from pharmacologjc experiments on the antihypoxic and anticonvulsant activities of flunarizine.…”

Section: Methodsmentioning

confidence: 99%

Photochemical stroke model: flunarizine prevents sensorimotor deficits after neocortical infarcts in rats.

Ryck

Reempts

Borgers

et al. 1989

Stroke

319

155

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We produced unilateral photochemical infarcts in the hindlimb sensorimotor neocortex of 186 rats by intravenous injection of the fluoroscein derivative rose bengal and focal illumination of the intact skull surface. Infarcted rats showed specific, long-lasting deficits in tactile and proprioceptive placing reactions of the contralateral limbs, mostly the hindlimb. Placing deficits were most prominent during transition to immobility and/or when independent limb movements were required. Administration of flunarizine, a Class FV calcium antagonist, 30 minutes after infarction resulted in marked sparing of sensorimotor function in 30 rats. In contrast to 20 vehicle-treated rats, which remained deficient for at least 21 days, 15 (75%) of the rats treated with 1.25 mg/kg i.v. flunarizine showed normal placing on Day 1 after infarction, whereas the remaining five (25%) recovered within 5 days. Oral treatment of 10 rats with 40 mg/kg flunarizine was also effective. Neocortical infarct volume and thalamic gliosis, assessed 21 days after infarction, did not differ between 30 flunarizine-and 30 vehicle-treated rats. However, when 4-hour-old infarcts were measured in 16 rats, posttreatment with intravenous flunarizine reduced infarct size by 31%. In combination with appropriate behavioral analyses, photochemical thrombosis may constitute a relevant stroke model, in which flunarizine preserved behavioral function during a critical period, corresponding to the spread of ischemic damage. {Stroke 1989;20:1383-1390) W hen the fluorescein derivative rose bengal is intravenously injected into rats and the intact skull surface is focally illuminated, cerebral blood vessels in a confined area sustain photochemical injury. Singlet oxygen molecules generated by the dye/light interaction cause peroxidation of endothelial cell membranes and occlusive platelet aggregation. Subsequent thrombus formation, vascular stasis, extravasation, and cytotoxic edema lead to cerebral infarction and necrosis. 1-2 This photochemical model of thrombotic stroke is virtually noninvasive, allows for reproducible infarct size and location, and includes endothelial damage/platelet aggregation interactions in a cascade of stroke-like ischemic events. In this model, the time course of changes in cerebral

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Section: Methodsmentioning

confidence: 99%