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Post‐treatment with cocaine‐ and amphetamine‐regulated transcript enhances infarct resolution,reinnervation, and angiogenesis in stroke rats – an MRI study
Authors:H.‐S. Liu  H. Shen  Y. Luo  B. J. Hoffer  Y. Wang  Y. Yang
Affiliation:1. Neuroimaging Research Branch, National Institute on Drug Abuse, National Institutes of Health, Baltimore, MD, USA;2. Graduate Institute of Clinical Medicine, College of Medicine, Taipei Medical University, Taipei, Taiwan;3. Department of Medical Imaging, Taipei Medical University Hospital, Taipei, Taiwan;4. Radiogenomic Research Center, Taipei Medical University Hospital, Taipei, Taiwan;5. Translational Imaging Research Center, Taipei, Taiwan;6. Synaptic Plasticity Section, Cellular Neurobiology Research Branch, National Institute on Drug Abuse, National Institutes of Health, Baltimore, MD, USA;7. Department of Neurological Surgery, Case Western Reserve University, Cleveland, OH, USA;8. Biomedical Research Center, National Institute on Drug Abuse, National Institutes of Health, Baltimore, MD, USA;9. Center for Neuropsychiatric Research, National Health Research Institutes, Zhunan, Miaoli County, Taiwan
Abstract:Recent studies have shown that post‐treatment with cocaine‐ and amphetamine‐regulated transcript (CART) has neuroregenerative effects in animal models of stroke. The purpose of this study was to characterize CART‐mediated neuronal and vascular repairments using non‐invasive MRI techniques. Adult male rats were subjected to a 90 min middle cerebral artery occlusion (MCAo). Animals were separated into two groups with similar infarction sizes, measured by T2‐weighted MRI on Day 2 after MCAo, and were treated with CART or vehicle intranasally from Day 3 to Day 12. Diffusion tensor imaging was used to examine changes in plasticity of white matter elements. Susceptibility‐weighted imaging (SWI) was used to measure angiogenesis. Post‐treatment with CART significantly increased fractional anisotropy (FA) in lesioned cortex on Days 10 and 25 post stroke. A significant correlation between the behavioral recovery in body asymmetry and the change in FA was shown, suggesting that behavioral recovery was associated with reinnervation to the lesioned hemisphere. CART also increased the intensity of SWI and the immunoreactivity of the vascular marker alpha‐smooth muscle actin in lesioned cortex. Together, our data support a non‐invasive treatment strategy for stroke through angiogenesis and reinnervation by CART. Copyright © 2016 John Wiley & Sons, Ltd.
Keywords:MRI  susceptibility‐weighted imaging  fractional anisotropy  cocaine‐ and amphetamine‐regulated transcript
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