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Long-term Motor Improvement After Stroke is Enhanced by Short-term Treatment With the Alpha2 Antagonist, Atipamezole

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Title: Long-term Motor Improvement After Stroke is Enhanced by Short-term Treatment With the Alpha2 Antagonist, Atipamezole
Author(s): Beltran, Erik J.; Papadopoulos, Catherine M.; Tsai, Shih-Yen; Kartje, Gwendolyn L.; Wolf, William A.
Subject(s): Adrenergic alpha-2 Receptor Agonists
Abstract: Drugs that increase central noradrenergic activity have been shown to enhance the rate of recovery of motor function in preclinical models of brain damage. Less is known about whether noradrenergic agents can improve the extent of motor recovery and whether such improvement can be sustained over time. This study was designed to determine if increasing central noradrenergic tone using atipamezole, an alpha2 adreneceptor antagonist, could induce a long-term improvement in motor performance in rats subjected to ischemic brain damage caused by permanent middle cerebral artery occlusion. The importance of pairing physical “rehabilitation” with enhanced noradrenergic activity was also investigated. Atipamezole (1 mg/kg, s.c.) or vehicle (sterile saline) was administered once daily on Days 2 – 8 post-operatively. Half of each drug group was housed under enriched environment conditions supplemented with daily focused activity sessions while the other half received standard housing with no focused activity. Skilled motor performance in forelimb reaching and ladder rung walking was assessed for 8 weeks post-operatively. Animals receiving atipamezole plus rehabilitation exhibited significantly greater motor improvement in both behavioral tests as compared to vehicle-treated animals receiving rehabilitation. Interestingly, animals receiving atipamezole without rehabilitation exhibited a significant motor improvement in the ladder rung walk test, but not the forelimb reaching test. These results suggest that a short-term increase in noradrenergic activity can lead to sustained motor improvement following stroke, especially when paired with rehabilitation.
Issue Date: 2010-07
Publisher: Elsevier
Citation Info: Beltran, E. J., Papadopoulos, C. M., Tsai, S. Y., Kartje, G. L., & Wolf, W. A. 2010. Long-term motor improvement after stroke is enhanced by short-term treatment with the alpha2 antagonist, atipamezole. Brain Research, 1346: 174-182. DOI: 10.1016/j.brainres.2010.05.063
Type: Article
Description: Postprint version of article may differ from published version. The definitive version is available through Elsevier at DOI: 10.1016/j.brainres.2010.05.063
ISSN: 0006-8993
Sponsor: Department of Veterans Affairs PHS
Date Available in INDIGO: 2011-01-10

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