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Cardiology Research and Practice
Volume 2012, Article ID 319230, 6 pages
http://dx.doi.org/10.1155/2012/319230
Research Article

Novel Neurovascular Protective Agents: Effects of INV-155, INV-157, INV-159, and INV-161 versus Lipoic Acid and Captopril in a Rat Stroke Model

1Department of Biomedical Sciences, University of Prince Edward Island, Charlottetown, PE, Canada C1A 4P3
2InVasc Therapeutics, Atlanta, GA 30084, USA
3Atlanta Vascular Research Foundation, 3562 Habersham at Northlake, Atlanta, GA 30084, USA

Received 1 July 2011; Revised 19 September 2011; Accepted 1 October 2011

Academic Editor: Anjali Arora

Copyright © 2012 Barry J. Connell et al. This is an open access article distributed under the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited.

Abstract

Background. Lipoic acid (LA), which has significant antioxidant properties, may also function as a potent neuroprotectant. The synthetic compounds INV-155, INV-157, INV-159, and INV-161 are physiochemical combinations of lipoic acid and captopril. We sought to determine if these compounds have neuroprotective potential following middle cerebral artery occlusion (MCAO) in rats. Methods. Male Sprague-Dawley rats were injected intravenously with captopril (1–50 mg/kg) 30 minutes prior to MCAO. Blood pressure, heart rate, baroreceptor reflex sensitivity, and infarct size were measured. In addition, dose response effect on infarct size and cardiovascular parameters was determined using INV-155, INV-157, INV-159, and INV-161 and compared to captopril and LA. Results. Pretreatment with captopril and LA at all doses tested was neuroprotective. The compounds INV-159 (0.5–10 mg/kg) and INV-161 (1–10 mg/kg) produced a significant,dose-dependent decrease in infarct size. In contrast, INV-155 and INV-157 had no effect on infarct size. Conclusions. Combined pretreatment with captopril potentiated the neuroprotective benefit observed following LA alone. Both INV-159 and INV-161 were also neuroprotective. These results suggest that patients taking combinations of captopril and LA, either as combination therapy or in the form of INV-159 or INV-161, may also benefit from significant protection against cerebral infarction.