title: Improvement of the circulatory function partially accounts for the neuroprotective action of the phytoestrogen genistein in experimental ischemic stroke.
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 (β-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.
authors: Instituto de Investigación Sanitaria Hospital La Fe, Unidad Mixta de Investigación Cerebrovascular, Centro de Investigación, Ave. Campanar 21, 46009-Valencia, Spain.
authors: Belén
authors: B
authors: Cortina
authors: Germán
authors: G
authors: Torregrosa
authors: María
authors: M
authors: Castelló-Ruiz
authors: María C
authors: MC
authors: Burguete
authors: Antonio
authors: A
authors: Moscardó
authors: Ana
authors: A
authors: Latorre
authors: Juan B
authors: JB
authors: Salom
authors: Juana
authors: J
authors: Vallés
authors: María T
authors: MT
authors: Santos
authors: Enrique
authors: E
authors: Alborch
mesh_terms: D000818:Animals; D002545:Brain Ischemia / Q000150:complications / Q000188:drug therapy* / Q000378:metabolism / Q000473:pathology; D019833:Genistein / Q000097:blood / Q000494:pharmacology / Q000627:therapeutic use*; D008297:Male; D018696:Neuroprotective Agents / Q000097:blood / Q000494:pharmacology / Q000627:therapeutic use*; D048789:Phytoestrogens / Q000097:blood / Q000494:pharmacology / Q000627:therapeutic use*; D010974:Platelet Aggregation / Q000187:drug effects; D051381:Rats; D017208:Rats, Wistar; D020521:Stroke / Q000188:drug therapy* / Q000209:etiology / Q000378:metabolism / Q000473:pathology; D013928:Thromboxane A2 / Q000378:metabolism
chemical_list: D018696:Neuroprotective Agents; D048789:Phytoestrogens; D013928:Thromboxane A2; D019833:Genistein