Search for stroke-protecting agents in endothelin-1-induced ischemic stroke model in rats

Juris Rumaks, Jolanta Pupure, Simons Svirskis, Sergejs Isajevs, Gunars Duburs, Ivars Kalvinsh, Vija Klusa

Research output: Contribution to journalArticlepeer-review

10 Citations (Scopus)

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.

Original languageEnglish
Pages (from-to)525-531
Number of pages7
JournalMedicina (Lithuania)
Volume48
Issue number10
DOIs
Publication statusPublished - 2012
Externally publishedYes

Keywords*

  • Cerebrocrast
  • Endothelin-1
  • Ischemic stroke
  • Mildronate
  • Neurodegeneration
  • Protection

Field of Science*

  • 3.1 Basic medicine
  • 3.2 Clinical medicine

Publication Type*

  • 1.1. Scientific article indexed in Web of Science and/or Scopus database

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