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Open AccessArticle

Search for Stroke-Protecting Agents in Endothelin-1-Induced Ischemic Stroke Model in Rats

1
Faculty of Medicine, University of Latvia
2
Latvian Institute of Organic Synthesis, Latvia
*
Author to whom correspondence should be addressed.
Medicina 2012, 48(10), 77; https://doi.org/10.3390/medicina48100077
Received: 27 January 2012 / Accepted: 27 August 2012 / Published: 1 September 2012
Background and Objective. Ischemic stroke may initiate a reperfusion injury leading to brain damage cascades where inflammatory mechanisms play a major role. Therefore, the necessity 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 drugs administered 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.
Keywords: endothelin-1; ischemic stroke; neurodegeneration; protection; cerebrocrast; mildronate endothelin-1; ischemic stroke; neurodegeneration; protection; cerebrocrast; mildronate
MDPI and ACS Style

Rumaks, J.; Pupure, J.; Svirskis, S.; Isajevs, S.; Duburs, G.; Kalvinsh, I.; Klusa, V. Search for Stroke-Protecting Agents in Endothelin-1-Induced Ischemic Stroke Model in Rats. Medicina 2012, 48, 77.

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