NDLI: Sequential Therapy with Minocycline and Candesartan Improves Long-Term Recovery After Experimental Stroke

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Sequential Therapy with Minocycline and Candesartan Improves Long-Term Recovery After Experimental Stroke

Content Provider	Springer Nature Link
Author	Soliman, Sahar Ishrat, Tauheed Fouda, Abdelrahman Y. Patel, Ami Pillai, Bindu Fagan, Susan C.
Copyright Year	2015
Abstract	Minocycline and candesartan have both shown promise as candidate therapeutics in ischemic stroke, with multiple, and somewhat contrasting, molecular mechanisms. Minocycline is an anti-inflammatory, antioxidant, and anti-apoptotic agent and a known inhibitor of matrix metalloproteinases (MMPs). Yet, minocycline exerts antiangiogenic effects both in vivo and in vitro. Candesartan promotes angiogenesis and activates MMPs. Aligning these therapies with the dynamic processes of injury and repair after ischemia is likely to improve success of treatment. In this study, we hypothesize that opposing actions of minocycline and candesartan on angiogenesis, when administered simultaneously, will reduce the benefit of candesartan treatment. Therefore, we propose a sequential combination treatment regimen to yield a better outcome and preserve the proangiogenic potential of candesartan. In vitro angiogenesis was assessed using human brain endothelial cells. In vivo, Wistar rats subjected to 90-min middle cerebral artery occlusion (MCAO) were randomized into four groups: saline, candesartan, minocycline, and sequential combination of minocycline and candesartan. Neurobehavioral tests were performed 1, 3, 7, and 14 days after stroke. Brain tissue was collected on day 14 for assessment of infarct size and vascular density. Minocycline, when added simultaneously, decreased the proangiogenic effect of candesartan treatment in vitro. Sequential treatment, however, preserved the proangiogenic potential of candesartan both in vivo and in vitro, improved neurobehavioral outcome, and reduced infarct size. Sequential combination therapy with minocycline and candesartan improves long-term recovery and maintains candesartan’s proangiogenic potential.
Starting Page	309
Ending Page	322
Page Count	14
File Format	PDF
ISSN	18684483
Journal	Translational Stroke Research
Volume Number	6
Issue Number	4
e-ISSN	1868601X
Language	English
Publisher	Springer US
Publisher Date	2015-05-26
Publisher Place	New York
Access Restriction	One Nation One Subscription (ONOS)
Subject Keyword	ARBs Candesartan Minocycline Stroke Recovery Angiogenesis Neurosciences Neurology Cardiology Neurosurgery Vascular Surgery
Content Type	Text
Resource Type	Article
Subject	Cardiology and Cardiovascular Medicine Neuroscience Neurology (clinical)

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