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Während Frauen in der Allgemeinbevölkerung ein höheres Depressionsrisiko aufweisen als Männer, ist die Forschungslage zu Geschlechterunterschieden nach Schlaganfall heterogen. Die vorliegende Längsschnittstudie untersucht Geschlechterunterschiede in der Häufigkeit von depressiven Störungen und Symptomen nach Schlaganfall. An zwei deutschen Rehabilitationszentren wurden N = 174 Schlaganfallpatienten und -patientinnen1 (n = 72 weiblich) rekrutiert und etablierte Risikofaktoren erfasst. Nacherhebungen fanden nach acht und 15 Monaten statt. Depressive Störungen und Symptome waren häufiger bei Frauen (48.2 %) als bei Männern (28.3 %) während der stationären Rehabilitation, jedoch nicht in den Folgeuntersuchungen. Etablierte Risikofaktoren beeinflussten geschlechtsunabhängig die Ausprägung depressiver Symptomatik. In Übereinstimmung mit aktuellen Meta-Analysen zeigten sich keine dauerhaften Geschlechterunterschiede bei Depression nach Schlaganfall. In der klinischen Praxis sollte die Affektlage von Schlaganfallpatienten geschlechtsunabhängig betrachtet werden.
Objectives: Stroke, frequently a consequence of hypertension, is one of the leading causes of death and neurological disabilities worldwide. In the ischemic brain, levels of endothelin-1, one of the most potent vasoconstrictors, are raised. Anti-inflammatory and neuroprotective effects of endothelin antagonists after stroke have been described in literature. Based on these findings, we investigated the protective effect of the endothelin converting enzyme/neutral endopeptidase blocker, SLV 338, in salt-loaded, stroke-prone, spontaneously hypertensive rats.
Methods: Male, 8-week-old spontaneously hypertensive stroke-prone rats were put on a high salt diet and treated with either 30 mg/kg or 100 mg/kg SLV 338 or vehicle for 27 weeks. Blood pressure, neurological outcome, body weight, and mortality were investigated throughout treatment. In weeks 1 and 9, animals were housed in metabolic cages for collection of urinary and blood samples and assessment of salt water and food intake. In weeks 22 and 27, additional blood samples were taken. At the end of the study, all brains were analyzed using magnetic resonance imaging.
Results: SLV 338 was well tolerated in all animals. Neurological outcome and infarct size were similar in all groups. Albuminuria was considerably delayed and the incidence of stroke significantly lowered in treated animals. In spontaneously hypertensive stroke-prone rats, treatment with SLV 338 significantly (P=0.01) improved survival in comparison to the vehicle treated group in a blood pressure-independent manner.
Discussion: Our data in spontaneously hypertensive stroke-prone rats demonstrate that combined endothelin converting enzyme/neutral endopeptidase inhibition could offer a new therapeutic approach for primary stroke prevention and improvement of mortality. The mechanism seems to be blood pressure-independent.