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      Multimodal Magnetic Resonance Imaging and Therapeutic Intervention With Yi-nao-jie-yu Decoction in a Rat Model of Post-stroke Depression

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          Abstract

          Post-stroke depression (PSD) is the most common neuropsychiatric complication after a stroke, though its neuropathological characteristics have not been fully elucidated. Comprehensive and non-invasive magnetic resonance (MR) assessment techniques are urgently needed for current research, as diffusion tensor imaging (DTI), arterial spin labeling (ASL), and magnetic resonance spectroscopy (MRS) can allow for a comprehensive assessment of neuropathological changes in the brain. These techniques can provide information about microscopic tissue integrity, cerebral perfusion, and cerebral metabolism, and can serve as powerful tools for investigating neurophysiological changes associated with PSD. Yi-nao-jie-yu decoction (YNJYD) is a Chinese herbal formulation based on the theory of traditional Chinese medicine, with demonstrated clinical efficacy in the treatment of PSD. The aim of this study was to use these MR techniques to evaluate changes in PSD and YNJYD-treated rats. This is the first experimental study in animals to investigate neuropathological changes associated with PSD using a combination of multiple MR techniques, including DTI, ASL, and MRS. In addition, we investigated the effect of YNJYD in a rat model of PSD by assessing changes in brain tissue microstructure, brain metabolism, and cerebral perfusion. First, depressive-like behaviors of PSD rats were assessed by the open field test (OFT), sucrose preference test (SPT), and Morris water maze (MWM) test, and then the integrity of the rats' microstructure was assessed by DTI, the levels of regional cerebral perfusion were assessed by ASL, and changes in the relative concentrations of brain metabolites were determined by MRS. The results showed that OFT and SPT scores were significantly reduced in PSD rats, as was performance in the MWM; these PSD-associated changes were attenuated in rats administered YNJYD, with improved depressive-like behaviors evidenced by increased OFT and SPT scores and improved performance in the MWM task. Furthermore, we found that PSD rats had lower perfusion levels in the prefrontal cortex (PFC) and hippocampus (HP), microstructural damage, and abnormal changes in the concentrations of brain metabolites; YNJYD exerted therapeutic effects on PSD rats by improving microcirculation in the PFC and HP, regulating glutamatergic systems and membrane phospholipid metabolism, and repairing microstructural damage.

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          Most cited references48

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          Neurovascular coupling in the normal brain and in hypertension, stroke, and Alzheimer disease.

          The brain is critically dependent on a continuous supply of blood to function. Therefore, the cerebral vasculature is endowed with neurovascular control mechanisms that assure that the blood supply of the brain is commensurate to the energy needs of its cellular constituents. The regulation of cerebral blood flow (CBF) during brain activity involves the coordinated interaction of neurons, glia, and vascular cells. Thus, whereas neurons and glia generate the signals initiating the vasodilation, endothelial cells, pericytes, and smooth muscle cells act in concert to transduce these signals into carefully orchestrated vascular changes that lead to CBF increases focused to the activated area and temporally linked to the period of activation. Neurovascular coupling is disrupted in pathological conditions, such as hypertension, Alzheimer disease, and ischemic stroke. Consequently, CBF is no longer matched to the metabolic requirements of the tissue. This cerebrovascular dysregulation is mediated in large part by the deleterious action of reactive oxygen species on cerebral blood vessels. A major source of cerebral vascular radicals in models of hypertension and Alzheimer disease is the enzyme NADPH oxidase. These findings, collectively, highlight the importance of neurovascular coupling to the health of the normal brain and suggest a therapeutic target for improving brain function in pathologies associated with cerebrovascular dysfunction.
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            Post-Stroke Depression: A Review.

            Poststroke depression (PSD) has been recognized by psychiatrists for more than 100 years, but controlled systematic studies did not begin until the 1970s. Meta-analyses addressing almost all major clinical issues in the field have emerged because of the relatively small number of patients included in some stroke studies. In order to build large databases, these meta-analyses have merged patients with rigorously assessed mood disorders with major depressive features with patients scoring above arbitrary cutoff points on depression rating scales, thus missing important findings such as cognitive impairment associated with major but not minor depression. Nevertheless, PSD occurs in a significant number of patients and constitutes an important complication of stroke, leading to greater disability as well as increased mortality. The most clinically important advances, however, have been in the treatment and prevention of PSD. Recent meta-analyses of randomized controlled trials for the treatment of PSD have demonstrated the efficacy of antidepressants. Similarly, randomized controlled trials for prevention of PSD have shown that antidepressants significantly decrease the incidence of PSD compared with placebo. Early antidepressant treatment of PSD appears to enhance both physical and cognitive recovery from stroke and might increase survival up to 10 years following stroke. There has also been progress in understanding the pathophysiology of PSD. Inflammatory processes might be associated with the onset of at least some depressive symptoms. In addition, genetic and epigenetic variations, white matter disease, cerebrovascular deregulation, altered neuroplasticity, and changes in glutamate neurotransmission might be relevant etiological factors. Further elucidation of the mechanism of PSD may ultimately lead to specific targeted treatments.
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              Post-stroke depression: Mechanisms and pharmacological treatment

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                Author and article information

                Contributors
                Journal
                Front Psychiatry
                Front Psychiatry
                Front. Psychiatry
                Frontiers in Psychiatry
                Frontiers Media S.A.
                1664-0640
                04 November 2020
                2020
                : 11
                : 557423
                Affiliations
                [1] 1Beijing University of Chinese Medicine , Beijing, China
                [2] 2Department of Pediatrics, Third Affiliated Hospital, Beijing University of Chinese Medicine , Beijing, China
                [3] 3Department of Neurology, Beijing Hospital of Traditional Chinese Medicine Shunyi Branch , Beijing, China
                [4] 4Department of Cardiology, Third Affiliated Hospital, Beijing University of Chinese Medicine , Beijing, China
                [5] 5Department of Encephalopathy, Third Affiliated Hospital, Beijing University of Chinese Medicine , Beijing, China
                [6] 6School of Acupuncture-Moxibustion and Tuina, Beijing University of Chinese Medicine , Beijing, China
                [7] 7Center for Medical Experiments and Testing, Capital Medical University , Beijing, China
                [8] 8School of Traditional Chinese Medicine, Beijing University of Chinese Medicine , Beijing, China
                [9] 9Center of Treating Potential Diseases, Third Affiliated Hospital, Beijing University of Chinese Medicine , Beijing, China
                Author notes

                Edited by: Yuan-Pang Wang, University of São Paulo, Brazil

                Reviewed by: Binbin Nie, Chinese Academy of Sciences, China; Chien-Han Lai, National Yang-Ming University, Taiwan

                *Correspondence: Qisheng Tang tqsbucm@ 123456126.com

                This article was submitted to Mood and Anxiety Disorders, a section of the journal Frontiers in Psychiatry

                Article
                10.3389/fpsyt.2020.557423
                7672154
                33329096
                19e53ce8-96cc-4a14-8f10-cfeba8298113
                Copyright © 2020 Zhao, Zhang, Zhang, Zhao, Zheng, Tian, Lei, Liu, Zhao and Tang.

                This is an open-access article distributed under the terms of the Creative Commons Attribution License (CC BY). The use, distribution or reproduction in other forums is permitted, provided the original author(s) and the copyright owner(s) are credited and that the original publication in this journal is cited, in accordance with accepted academic practice. No use, distribution or reproduction is permitted which does not comply with these terms.

                History
                : 01 May 2020
                : 09 September 2020
                Page count
                Figures: 9, Tables: 0, Equations: 0, References: 48, Pages: 14, Words: 8641
                Categories
                Psychiatry
                Original Research

                Clinical Psychology & Psychiatry
                post-stroke depression,diffusion tensor imaging,arterial spin labeling,magnetic resonance spectroscopy,yi-nao-jie-yu decoction,traditional chinese medicine

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