Please use this identifier to cite or link to this item:
10.3390/medicina48100077
Title: | Search for stroke-protecting agents in endothelin-1-induced ischemic stroke model in rats |
Authors: | Rumaks, Juris Pupure, Jolanta Svirskis, Simons Isajevs, Sergejs Duburs, Gunars Kalvinsh, Ivars Klusa, Vija |
Keywords: | Cerebrocrast;Endothelin-1;Ischemic stroke;Mildronate;Neurodegeneration;Protection;3.1 Basic medicine;3.2 Clinical medicine;1.1. Scientific article indexed in Web of Science and/or Scopus database;General Medicine |
Issue Date: | 2012 |
Citation: | Rumaks , J , Pupure , J , Svirskis , S , Isajevs , S , Duburs , G , Kalvinsh , I & Klusa , V 2012 , ' Search for stroke-protecting agents in endothelin-1-induced ischemic stroke model in rats ' , Medicina (Lithuania) , vol. 48 , no. 10 , pp. 525-531 . https://doi.org/10.3390/medicina48100077 |
Abstract: | Background and Objective. Ischemic stroke may initiate a reperfusion injury leadingto brain damage cascades where inflammatory mechanisms play a major role. Therefore, thenecessity for the novel stroke-protecting agents whose the mechanism of action is focused on their anti-inflammatory potency is still on the agenda for drug designers. Our previous studies demonstrated that cerebrocrast (a 1,4-dihydropyridine derivative) and mildronate (a representative of the aza-butyrobetaine class) possessed considerable anti-inflammatory and neuroprotective properties in different in vitro and in vivo model systems.The present study investigated their stroke-protecting ability in an endothelin-1 (ET-1)-induced ischemic stroke model in rats. Material and Methods. Male Wistar rats were pretreated (for 7 days, per os) with cerebrocrast (0.1 mg/kg), mildronate (100 mg/kg), or their combination, followed by the intracerebral injection of ET-1. Functional and behavioral tests were carried out up to 14 days after the ET-1 injection. Ex vivo, the number of degenerated neurons and the infarction size in the cerebral cortical tissue were assessed histologically. Results. Cerebrocrast and mildronate effectively normalized ET-1-induced disturbances in neurological status, improved the muscle tone, and decreased the number of degenerated cortical cells. Both drugs also reduced the infarction size, and cerebrocrast showed at least a 2-fold higher activity than mildronate. The combination of both drugs did not cause a more pronounced effect in comparison with the action of drugsadministered separately. Conclusions. The 1,4-dihydropyridine and aza-butyrobetaine structures may serve for the design of novel stroke-protecting agents to prevent severe neurological poststroke consequences. |
DOI: | 10.3390/medicina48100077 |
ISSN: | 1010-660X |
Appears in Collections: | Research outputs from Pure / Zinātniskās darbības rezultāti no ZDIS Pure |
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