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      Expression changes of CX3CL1 and CX3CR1 proteins in the hippocampal CA1 field of the gerbil following transient global cerebral ischemia

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          Abstract

          Chemokine C-X3-C motif ligand 1 (CX3CL1) and its sole receptor, CX3CR1, are known to be involved in neuronal damage/death following brain ischemia. In the present study, time-dependent expression changes of CX3CL1 and CX3CR1 proteins were investigated in the hippocampal CA1 field following 5 min of transient global cerebral ischemia (tgCI) in gerbils. To induce tgCI in gerbils, bilateral common carotid arteries were occluded for 5 min using aneurysm clips. Expression changes of CX3CL1 and CX3CR1 proteins were assessed at 1, 2 and 5 days after tgCI using western blotting and immunohistochemistry. CX3CL1 immunoreactivity was strong in the CA1 pyramidal cells of animals in the sham operation group. Weak CX3CL1 immunoreactivity was detected at 6 h after tgCI, recovered at 1 day after tgCI and disappeared from 5 days after tgCI. CX3CR1 immunoreactivity was very weak in CA1 pyramidal cells of the sham animals. CX3CR1 immunoreactivity in CA1 pyramidal cells was significantly increased at 1 days after tgCI and gradually decreased thereafter. On the other hand, CX3CR1 immunoreactivity was significantly increased in microglia from 5 days after tgCI. These results showed that CX3CL1 and CX3CR1 protein expression levels in pyramidal cells and microglia in the hippocampal CA1 field following tgCI were changed, indicating that tgCI-induced expression changes of CX3CL1 and CX3CR1 proteins might be closely associated with tgCI-induced delayed neuronal death and microglial activation.

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          Most cited references41

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          Fluoro-Jade B: a high affinity fluorescent marker for the localization of neuronal degeneration.

          Fluoro-Jade B, like its predecessor Fluoro-Jade, is an anionic fluorescein derivative useful for the histological staining of neurons undergoing degeneration. However, Fluoro-Jade B has an even greater specific affinity for degenerating neurons. This notion is supported by the conspicuous staining of degenerating neuronal elements with minimal background staining. This improved signal-to-noise ratio means that fine neuronal processes including distal dendrites, axons and axon terminals can be more readily detected and documented. Although the staining time and dye concentration are reduced, the method is as rapid, simple and reliable as the original Fluoro-Jade technique. Like Fluoro-Jade, Fluoro-Jade B is compatible with a number of other labeling procedures including immunofluorescent and fluorescent Nissl techniques.
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            Inflammatory mediators and stroke: new opportunities for novel therapeutics.

            Contrary to previous dogmas, it is now well established that brain cells can produce cytokines and chemokines, and can express adhesion molecules that enable an in situ inflammatory reaction. The accumulation of neutrophils early after brain injury is believed to contribute to the degree of brain tissue loss. Support for this hypothesis has been drawn from many studies where neutrophil-depletion blockade of endothelial-leukocyte interactions has been achieved by various techniques. The inflammation reaction is an attractive pharmacologic opportunity, considering its rapid initiation and progression over many hours after stroke and its contribution to evolution of tissue injury. While the expression of inflammatory cytokines that may contribute to ischemic injury has been repeatedly demonstrated, cytokines may also provide "neuroprotection" in certain conditions by promoting growth, repair, and ultimately, enhanced functional recovery. Significant additional basic work is required to understand the dynamic, complex, and time-dependent destructive and protective processes associated with inflammation mediators produced after brain injury. The realization that brain ischemia and trauma elicit robust inflammation in the brain provides fertile ground for discovery of novel therapeutic agents for stroke and neurotrauma. Inhibition of the mitogen-activated protein kinase (MAPK) cascade via cytokine suppressive anti-inflammatory drugs, which block p38 MAPK and hence the production of interleukin-1 and tumor necrosis factor-alpha, are most promising new opportunities. However, spatial and temporal considerations need to be exercised to elucidate the best opportunities for selective inhibitors for specific inflammatory mediators.
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              Role for neuronally derived fractalkine in mediating interactions between neurons and CX3CR1-expressing microglia

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                Author and article information

                Journal
                Int J Mol Med
                Int. J. Mol. Med
                IJMM
                International Journal of Molecular Medicine
                D.A. Spandidos
                1107-3756
                1791-244X
                September 2019
                10 July 2019
                10 July 2019
                : 44
                : 3
                : 939-948
                Affiliations
                [1 ]Department of Biomedical Science, Research Institute of Bioscience and Biotechnology, Hallym University, Chuncheon, Gangwon 24252
                [2 ]Department of Biochemistry and Molecular Biology, and Research Institute of Oral Sciences, College of Dentistry, Gangnung-Wonju National University, Gangneung, Gangwon 25457
                [3 ]Department of Neurobiology
                [4 ]Departments of Obstetrics and Gynecology, School of Medicine, Kangwon National University, Chuncheon, Gangwon 24341
                [5 ]Department of Pharmacy, College of Pharmacy, Dankook University, Cheonan, Chungcheongnam 31116, Republic of Korea
                Author notes
                Correspondence to: Professor Moo-Ho Won, Department of Neurobiology, School of Medicine, Kangwon National University, 1 Gangwondaehak, Chuncheon, Gangwon 24341, Republic of Korea, E-mail: mhwon@ 123456kangwon.ac.kr
                Professor Choong-Hyun Lee, Department of Pharmacy, College of Pharmacy, Dankook University, 119 Dandae-ro, Cheonan, Chungcheongnam 31116, Republic of Korea, E-mail: anaphy@ 123456dankook.ac.kr
                [*]

                Contributed equally

                Article
                ijmm-44-03-0939
                10.3892/ijmm.2019.4273
                6658004
                405e2b31-5c00-4857-bf6c-859b1e426482
                Copyright: © Ahn et al.

                This is an open access article distributed under the terms of the Creative Commons Attribution-NonCommercial-NoDerivs License, which permits use and distribution in any medium, provided the original work is properly cited, the use is non-commercial and no modifications or adaptations are made.

                History
                : 19 March 2019
                : 08 July 2019
                Categories
                Articles

                cx3cl1,cx3cr1,delayed neuronal death,microglial activation,transient global cerebral ischemia

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