Improvement of the circulatory function partially accounts for the neuroprotective action of the phytoestrogen genistein in experimental ischemic stroke.

Autores de IIS La Fe

• Belen Cortina Gil

  Autor

• Germán Torregrosa Bernabé

  Autor

• María Castelló Ruiz

  Autor

• María Consuelo Burguete López

  Autor

• Antonio Moscardó Martínez

  Autor

• Ana María Latorre Campos

  Autor

• Juan Bautista Salom Sanvalero

  Autor

• Juana Valles Giner

  Autor

• Maria Teresa Santos Diaz

  Autor

• Enrique Alborch Domínguez

  Autor

Grupos

• Hemostasia, Trombosis, Arteriosclerosis y Biología vascular

• Unidad Mixta de Investigación Cerebrovascular

Abstract

We tested the hypothesis that the phytoestrogen genistein protects the brain against ischemic stroke by improving the circulatory function in terms of reduced production of thromboxane A2 and leukocyte-platelet aggregates, and of preserved vascular reactivity. Ischemia-reperfusion (90 min-3 days, intraluminal filament) was induced in male Wistar rats, and functional score and cerebral infarct volume were the end points examined. Genistein (10mg/kg/day) or vehicle (ß-cyclodextrin) was administered at 30 min after ischemia or sham-operation. Production of thromboxane A2 and leukocyte-platelet aggregates, as well as reactivity of carotid artery to U-46619 (thromboxane A2 analogue) and to platelet releasate was measured. At 3 days post-ischemia, both improvement in the functional examination and reduction in the total infarct volume were shown in the ischemic genistein-treated group. Genistein significantly reverted both the increased thromboxane A2 concentration and the increased leukocyte-platelet aggregates production found in samples from the ischemic vehicle-treated group. Both U-46619 and platelet releasate elicited contractions of the carotid artery, which were significantly lower in the ischemic vehicle-treated group. Genistein significantly restored both the decreased U-46619- and the decreased platelet releasate-elicited contractile responses. In conclusion, genistein protects the brain against an ischemia-reperfusion challenge, at least in part, by its beneficial effects on the circulatory function.