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

Sahar Soliman, Tauheed Ishrat, Abdelrahman Y. Fouda, Ami Patel, Bindu Pillai, Susan C. Fagan

Research output: Contribution to journalArticle

20 Citations (Scopus)

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.

Original languageEnglish (US)
Pages (from-to)309-322
Number of pages14
JournalTranslational Stroke Research
Volume6
Issue number4
DOIs
StatePublished - Aug 1 2015
Externally publishedYes

Fingerprint

Minocycline
Stroke
Therapeutics
candesartan
Matrix Metalloproteinase Inhibitors
Middle Cerebral Artery Infarction
Brain
Matrix Metalloproteinases
Blood Vessels
Wistar Rats
Anti-Inflammatory Agents
Ischemia
Endothelial Cells
Antioxidants

All Science Journal Classification (ASJC) codes

  • Neuroscience(all)
  • Clinical Neurology
  • Cardiology and Cardiovascular Medicine

Cite this

Sequential Therapy with Minocycline and Candesartan Improves Long-Term Recovery After Experimental Stroke. / Soliman, Sahar; Ishrat, Tauheed; Fouda, Abdelrahman Y.; Patel, Ami; Pillai, Bindu; Fagan, Susan C.

In: Translational Stroke Research, Vol. 6, No. 4, 01.08.2015, p. 309-322.

Research output: Contribution to journalArticle

Soliman, Sahar ; Ishrat, Tauheed ; Fouda, Abdelrahman Y. ; Patel, Ami ; Pillai, Bindu ; Fagan, Susan C. / Sequential Therapy with Minocycline and Candesartan Improves Long-Term Recovery After Experimental Stroke. In: Translational Stroke Research. 2015 ; Vol. 6, No. 4. pp. 309-322.
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