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Microglia and migration

M Asunción Barreda-Manso, Natalia Yanguas-Casás, Manuel Nieto-Sampedro, Lorenzo Romero-Ramírez
Following a central nervous system (CNS) injury, restoration of the blood-brain barrier (BBB) integrity is essential for recovering homeostasis. When this process is delayed or impeded, blood substances and cells enter the CNS parenchyma, initiating an additional inflammatory process that extends the initial injury and causes so-called secondary neuronal loss. Astrocytes and profibrotic mesenchymal cells react to the injury and migrate to the lesion site, creating a new glia limitans that restores the BBB. This process is beneficial for the resolution of the inflammation, neuronal survival and the initiation of the healing process...
October 18, 2016: Journal of Cellular Physiology
Jun Udagawa, Kodai Hino
Epidemiological studies suggest that exposure to prenatal stressors, including malnutrition, maternal immune activation (MIA), and adverse life events, is associated with increased risks of schizophrenia, autism spectrum disorder (ASD), and attention-deficit hyperactivity disorder (ADHD). However, the underlying pathophysiological mechanisms are unclear. The first trimester of pregnancy is particularly a vulnerable period. During this period, the self-renewal of neural stem cells and neurogenesis vigorously occur, and synaptic connections are partially formed in the telencephalon...
2016: Nihon Eiseigaku Zasshi. Japanese Journal of Hygiene
Frances Corrigan, Kimberley A Mander, Anna V Leonard, Robert Vink
BACKGROUND: The neuroinflammatory response following traumatic brain injury (TBI) is known to be a key secondary injury factor that can drive ongoing neuronal injury. Despite this, treatments that have targeted aspects of the inflammatory pathway have not shown significant efficacy in clinical trials. MAIN BODY: We suggest that this may be because classical inflammation only represents part of the story, with activation of neurogenic inflammation potentially one of the key initiating inflammatory events following TBI...
October 11, 2016: Journal of Neuroinflammation
Marija Adzic, Ivana Stevanovic, Natasa Josipovic, Danijela Laketa, Irena Lavrnja, Ivana M Bjelobaba, Iva Bozic, Marija Jovanovic, Milena Milosevic, Nadezda Nedeljkovic
It is widely accepted that adenosine triphosphate (ATP) acts as a universal danger-associated molecular pattern with several known mechanisms for immune cell activation. In the central nervous system, ATP activates microglia and astrocytes and induces a neuroinflammatory response. The aim of the present study was to describe responses of isolated astrocytes to increasing concentrations of ATP (5 µM to 1 mM), which were intended to mimic graded intensity of the extracellular stimulus. The results show that ATP induces graded activation response of astrocytes in terms of the cell proliferation, stellation, shape remodeling, and underlying actin and GFAP filament rearrangement, although the changes occurred without an apparent increase in GFAP and actin protein expression...
October 7, 2016: Journal of Neuroscience Research
Bernardo Castellano, Mar Bosch-Queralt, Beatriz Almolda, Nàdia Villacampa, Berta González
Microglial cells are highly dynamic cells with processes continuously moving to survey the surrounding territory. Microglia possess a broad variety of surface receptors and subtle changes in their microenvironment cause microglial cell processes to extend, retract, and interact with neuronal synaptic contacts. When the nervous system is disturbed, microglia activate, proliferate, and migrate to sites of injury in response to alert signals. Released nucleotides like ATP and UTP are among the wide range of molecules promoting microglial activation and guiding their migration and phagocytic function...
2016: Advances in Experimental Medicine and Biology
Zengyang Yu, Tianyu Zhang, Chenyuan Gong, Yuchen Sheng, Bin Lu, Lingyu Zhou, Lili Ji, Zhengtao Wang
Erianin is a natural compound found in Dendrobium chrysotoxum Lindl. Diabetic retinopathy (DR) is a serious and common microvascular complication of diabetes. This study aims to investigate the inhibitory mechanism of erianin on retinal neoangiogenesis and its contribution to the amelioration of DR. Erianin blocked high glucose (HG)-induced tube formation and migration in choroid-retinal endothelial RF/6A cells. Erianin inhibited HG-induced vascular endothelial growth factor (VEGF) expression, hypoxia-inducible factor 1-alpha (HIF-1α) translocation into nucleus and ERK1/2 activation in RF/6A and microglia BV-2 cells...
September 28, 2016: Scientific Reports
Jayson Hardcastle, Lisa Mills, Courtney S Malo, Fang Jin, Cheyne Kurokawa, Hirosha Geekiyanage, Mark Schroeder, Jann Sarkaria, Aaron J Johnson, Evanthia Galanis
BACKGROUND: Glioblastoma (GBM) is the most common primary malignant brain tumor and has a dismal prognosis. Measles virus (MV) therapy of GBM is a promising strategy due to preclinical efficacy, excellent clinical safety, and its ability to evoke antitumor pro-inflammatory responses. We hypothesized that combining anti- programmed cell death protein 1 (anti-PD-1) blockade and MV therapy can overcome immunosuppression and enhance immune effector cell responses against GBM, thus improving therapeutic outcome...
September 23, 2016: Neuro-oncology
Jin Hwan Lee, Zheng Z Wei, Wenyuan Cao, Soonmi Won, Xiaohuan Gu, Megan Winter, Thomas A Dix, Ling Wei, Shan Ping Yu
Stroke is a leading threat to human life and health in the US and around the globe, while very few effective treatments are available for stroke patients. Preclinical and clinical studies have shown that therapeutic hypothermia (TH) is a potential treatment for stroke. Using novel neurotensin receptor 1 (NTR1) agonists, we have demonstrated pharmacologically induced hypothermia and protective effects against brain damages after ischemic stroke, hemorrhage stroke, and traumatic brain injury (TBI) in rodent models...
September 19, 2016: Neurobiology of Disease
J I Yongjia, L U Hongzhou
With extended life of HIV-infected patients due to highly active anti-retroviral therapy (HAART), the rate of HIV associated neurocognitive disorder (HAND) remains high and attracts much attention. The evidence is clear that cytokines are elevated in the blood of patients with HIV infection, which contribute to elevating the permeability of blood-brain barrier. Benefiting from that, cells in the brain are infected with HIV that has accelerated through the blood-brain barrier both as cell-free virus and infected immune cells including monocytes and T cells...
May 25, 2016: Zhejiang da Xue Xue Bao. Yi Xue Ban, Journal of Zhejiang University. Medical Sciences
Ziyun Jiang, Qin Song, Mingliang Tang, Lingyan Yang, Yilin Cheng, Min Zhang, Dongsheng Xu, Guosheng Cheng
One of the key challenges in engineering neural tissues for cell-based therapies is to develop a biocompatible scaffold material to direct neural stem cell (NSC) behaviors. One great advantage for a scaffold would be to induce NSC migration toward pathological sites during regeneration and repair. In particular, the inflammatory responses in the pathological zone, which are mainly mediated by microglia in the central nervous system, affect the repair capacity of NSCs through NSC migration. Recently, graphene was used as a neural interface and scaffold material, but few studies have addressed the relationship between microglia and NSCs in a graphene culture system...
September 28, 2016: ACS Applied Materials & Interfaces
Rosana S Lopes, Marcelo M Cardoso, Arthur O Sampaio, Mario Santos Barbosa, Celice C Souza, Michelle C DA Silva, Elane Magno N Ferreira, Marco Aurelio M Freire, Rafael Rodrigues Lima, Walace Gomes-Leal
Neuroblasts from the subventricular zone (SVZ) migrate to striatum following stroke, but most of them die in the ischaemic milieu and this can be related to exacerbated microglial activation. Here, we explored the effects of the non-steroidal anti-inflammatory indomethacin on microglial activation, neuronal preservation and neuroblast migration following experimental striatal stroke in adult rats. Animals were submitted to endothelin-1 (ET-1)-induced focal striatal ischaemia and were treated with indomethacin or sterile saline (i...
September 2016: Journal of Biosciences
Masataka Ifuku, Alice Buonfiglioli, Philipp Jordan, Seija Lehnardt, Helmut Kettenmann
Microglial cells are the pathologic sensor of the brain, and any pathologic event triggers microglial activation, which involves migration of these cells to a lesion site. Employing different migration assays, we show that ligands for toll-like receptor (TLR) 2 stimulate random motility, while TLR7 ligands are chemoattractants. The subtype specificity of the TLR ligands was verified by using different TLR-deficient (TLRKO) mouse lines. PI3K and Rac inhibition impairs both TLR2- and TLR7-stimulated microglial migration...
November 2016: Brain, Behavior, and Immunity
Muskan Gupta, Gurcharan Kaur
BACKGROUND: Microglial-mediated neuroinflammation is a key factor underlying the pathogenesis of various neurodegenerative diseases and also an important target for the development of the neuroinflammation-targeted therapeutics. Conventionally, the nonsteroidal anti-inflammatory drugs (NSAIDs) are prescribed, but they are associated with long-term potential risks. Natural products are the cornerstone of modern therapeutics, and Ashwagandha is one such plant which is well known for its immunomodulatory properties in Ayurveda...
2016: Journal of Neuroinflammation
Yu Zhang, Ruinan Gu, Jia Jia, Tingjun Hou, Longtai Zheng, Xuechu Zhen
Macrophage migration inhibitory factor (MIF), a pleiotropic proinflammatory cytokine, is a key regulator in both innate and acquired immunity system. MIF has become a promising drug target for inflammatory diseases. Apart from its cytokine activities, MIF is known to act as a D-dopachrome tautomerase. Our previous work have identified that 3-[(biphenyl-4-ylcarbonyl)carbamothioyl]amino benzoic acid (Z-590) exhibited a potent inhibitory activity against MIF. In this study, we investigated the effect of Z-590 on lipopolysaccharide (LPS)-activated microglial cell activation...
August 20, 2016: Clinical and Experimental Pharmacology & Physiology
Esther Dalko, Delphine Genete, Florent Auger, Claire Dovergne, Claire Lambert, Fabien Herbert, Pierre-André Cazenave, Jacques Roland, Sylviane Pied
Cerebral malaria is the deadliest complication of Plasmodium falciparum infection. Its pathophysiology is associated with a strong pro-inflammatory reaction and the activation of glial cells. Among modulators released during the infection, heme seems to play a controversial role in the pathophysiology of malaria. Herein, we first investigated the phenotype of glial cells during cerebral malaria in C57BL/6 mice infected with P. berghei ANKA. Given the fact that high levels of heme were associated with cerebral malaria, we then investigated its impact on microglial, astrocyte, and T cell responses to further clarify its contribution in the neuropathophysiology...
November 2016: Brain, Behavior, and Immunity
Hideto Koso, Asano Tsuhako, Chen-Yi Lai, Yukihiro Baba, Makoto Otsu, Kazuko Ueno, Masao Nagasaki, Yutaka Suzuki, Sumiko Watanabe
Neurodegeneration has been shown to induce microglial activation and the infiltration of monocyte-derived macrophages into the CNS, resulting in the coexistence of these two populations within the same lesion, though their distinct features remain elusive. To investigate the impact of rod photoreceptor degeneration on microglial activation, we generated a toxin-mediated genetic model of rod degeneration. Rod injury induced microglial proliferation and migration toward the photoreceptors. Bone marrow transplantation revealed the invasion of monocyte-derived macrophages into the retina, with microglia and the infiltrating macrophages showing distinct distribution patterns in the retina...
November 2016: Glia
Francesca Boscia, Gulnaz Begum, Giuseppe Pignataro, Rossana Sirabella, Ornella Cuomo, Antonella Casamassa, Dandan Sun, Lucio Annunziato
Sodium dynamics are essential for regulating functional processes in glial cells. Indeed, glial Na(+) signaling influences and regulates important glial activities, and plays a role in neuron-glia interaction under physiological conditions or in response to injury of the central nervous system (CNS). Emerging studies indicate that Na(+) pumps and Na(+) -dependent ion transporters in astrocytes, microglia, and oligodendrocytes regulate Na(+) homeostasis and play a fundamental role in modulating glial activities in neurological diseases...
October 2016: Glia
Santiago Solé-Domènech, Dana L Cruz, Estibaliz Capetillo-Zarate, Frederick R Maxfield
Microglia, the main phagocytes of the central nervous system (CNS), are involved in the surveillance and maintenance of nervous tissue. During normal tissue homeostasis, microglia migrates within the CNS, phagocytose dead cells and tissue debris, and modulate synapse pruning and spine formation via controlled phagocytosis. In the event of an invasion by a foreign body, microglia are able to phagocytose the invading pathogen and process it proteolytically for antigen presentation. Internalized substrates are incorporated and sorted within the endocytic pathway and thereafter transported via complex vesicular routes...
July 12, 2016: Ageing Research Reviews
Emiliano Trias, Sofía Ibarburu, Romina Barreto-Núñez, Joël Babdor, Thiago T Maciel, Matthias Guillo, Laurent Gros, Patrice Dubreuil, Pablo Díaz-Amarilla, Patricia Cassina, Laura Martínez-Palma, Ivan C Moura, Joseph S Beckman, Olivier Hermine, Luis Barbeito
BACKGROUND: In the SOD1(G93A) mutant rat model of amyotrophic lateral sclerosis (ALS), neuronal death and rapid paralysis progression are associated with the emergence of activated aberrant glial cells that proliferate in the degenerating spinal cord. Whether pharmacological downregulation of such aberrant glial cells will decrease motor neuron death and prolong survival is unknown. We hypothesized that proliferation of aberrant glial cells is dependent on kinase receptor activation, and therefore, the tyrosine kinase inhibitor masitinib (AB1010) could potentially control neuroinflammation in the rat model of ALS...
2016: Journal of Neuroinflammation
Nicole Michelson, Jordina Rincon-Torroella, Alfredo Quiñones-Hinojosa, Jeffrey P Greenfield
Studies of inflammatory mediators have established the tumor micro-environment as a driver of oncogenesis. This inflammatory milieu often precedes cancer, however recent data also point to the ability of oncogenic changes to induce inflammatory responses that are later harnessed by the tumor to survive and proliferate. In this review, we propose that the IDH1 mutation, present in the majority of low-grade gliomas (LGGs), initiates an inflammatory cascade that is ultimately hijacked by the tumor. Glioma infiltrating macrophages and microglia (GIMs) are polarized to the M2 phenotype, subverting the host's adaptive immune response, and fostering a tumor milieu ripe for angiogenesis, migration, and metastasis...
August 15, 2016: Journal of Neuroimmunology
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