scholarly journals Circulating myeloid cells invade the central nervous system to mediate cachexia during pancreatic cancer

eLife ◽  
2020 ◽  
Vol 9 ◽  
Author(s):  
Kevin G Burfeind ◽  
Xinxia Zhu ◽  
Mason A Norgard ◽  
Peter R Levasseur ◽  
Christian Huisman ◽  
...  
Keyword(s):  
Central Nervous System ◽  
Nervous System ◽  
Immune Cell ◽  
Purinergic Receptor ◽  
Myeloid Cells ◽  
Myeloid Cell ◽  
Ductal Adenocarcinoma ◽  
The Central Nervous System ◽  
Velum Interpositum ◽  
The Brain

Weight loss and anorexia are common symptoms in cancer patients that occur prior to initiation of cancer therapy. Inflammation in the brain is a driver of these symptoms, yet cellular sources of neuroinflammation during malignancy are unknown. In a mouse model of pancreatic ductal adenocarcinoma (PDAC), we observed early and robust myeloid cell infiltration into the brain. Infiltrating immune cells were predominately neutrophils, which accumulated at a unique central nervous system entry portal called the velum interpositum, where they expressed CCR2. Pharmacologic CCR2 blockade and genetic deletion of Ccr2 both resulted in significantly decreased brain-infiltrating myeloid cells as well as attenuated cachexia during PDAC. Lastly, intracerebroventricular blockade of the purinergic receptor P2RX7 during PDAC abolished immune cell recruitment to the brain and attenuated anorexia. Our data demonstrate a novel function for the CCR2/CCL2 axis in recruiting neutrophils to the brain, which drives anorexia and muscle catabolism.

scholarly journals “A distinct neutrophil population invades the central nervous system during pancreatic cancer”

2019 ◽  
Author(s):  
Kevin G. Burfeind ◽  
Xinxia Zhu ◽  
Mason A. Norgard ◽  
Peter R. Levasseur ◽  
Brennan Olson ◽  
...  
Keyword(s):  
Central Nervous System ◽  
Nervous System ◽  
Immune Cells ◽  
Purinergic Receptor ◽  
Myeloid Cell ◽  
Ductal Adenocarcinoma ◽  
The Central Nervous System ◽  
Muscle Catabolism ◽  
Velum Interpositum ◽  
The Brain

AbstractWeight loss, fatigue, and cognitive dysfunction are common symptoms in cancer patients that occur prior to initiation of cancer therapy. Inflammation in the brain is a driver of these symptoms, yet cellular sources of neuroinflammation during malignancy are unknown. In a mouse model of pancreatic ductal adenocarcinoma (PDAC), we observed early and robust myeloid cell infiltration into the brain. Infiltrating immune cells were predominately neutrophils, which accumulated at a unique central nervous system entry portal called the velum interpositum, where they expressed CCR2. CCR2 knockout mice had significantly decreased brain-infiltrating neutrophils as well as attenuated anorexia and muscle catabolism during PDAC, without any changes in neutrophils in other organs. Lastly, intracerebroventricular blockade of the purinergic receptor P2RX7 during PDAC abolished neutrophil recruitment to the brain and attenuated anorexia. Our data demonstrate a novel function for the CCR2/CCL2 axis in recruiting neutrophils to the brain, which drives anorexia and muscle catabolism.

scholarly journals Immune System in the Brain: A Modulatory Role on Dendritic Spine Morphophysiology?

2012 ◽  
Vol 2012 ◽  
pp. 1-7 ◽  
Author(s):  
Oscar Kurt Bitzer-Quintero ◽  
Ignacio González-Burgos
Keyword(s):  
Central Nervous System ◽  
Nervous System ◽  
Immune System ◽  
Dendritic Spines ◽  
Cell Lineage ◽  
Myeloid Cell ◽  
Brain Parenchyma ◽  
Immune Mediators ◽  
The Central Nervous System ◽  
The Brain

The central nervous system is closely linked to the immune system at several levels. The brain parenchyma is separated from the periphery by the blood brain barrier, which under normal conditions prevents the entry of mediators such as activated leukocytes, antibodies, complement factors, and cytokines. The myeloid cell lineage plays a crucial role in the development of immune responses at the central level, and it comprises two main subtypes: (1) resident microglia, distributed throughout the brain parenchyma; (2) perivascular macrophages located in the brain capillaries of the basal lamina and the choroid plexus. In addition, astrocytes, oligodendrocytes, endothelial cells, and, to a lesser extent, neurons are implicated in the immune response in the central nervous system. By modulating synaptogenesis, microglia are most specifically involved in restoring neuronal connectivity following injury. These cells release immune mediators, such as cytokines, that modulate synaptic transmission and that alter the morphology of dendritic spines during the inflammatory process following injury. Thus, the expression and release of immune mediators in the brain parenchyma are closely linked to plastic morphophysiological changes in neuronal dendritic spines. Based on these observations, it has been proposed that these immune mediators are also implicated in learning and memory processes.

Myeloid cells: The Trojan horse for T cell invasion into the brain

2019 ◽  
Vol 11 (520) ◽  
pp. eaaz9757
Author(s):  
Gilbert Gallardo
Keyword(s):  
Central Nervous System ◽  
T Cells ◽  
Nervous System ◽  
Cell Invasion ◽  
Myeloid Cells ◽  
Autoimmune Encephalomyelitis ◽  
Lectin Receptors ◽  
The Central Nervous System ◽  
The Brain ◽  
Experimental Autoimmune

C-type lectin receptors on myeloid cells regulate the activation and infiltration of T cells into the central nervous system in experimental autoimmune encephalomyelitis.

scholarly journals Physiology of Microglia

2011 ◽  
Vol 91 (2) ◽  
pp. 461-553 ◽  
Author(s):  
Helmut Kettenmann ◽  
Uwe-Karsten Hanisch ◽  
Mami Noda ◽  
Alexei Verkhratsky
Keyword(s):  
Central Nervous System ◽  
Nervous System ◽  
Immune Cell ◽  
Brain Parenchyma ◽  
Microglial Cells ◽  
Activation Process ◽  
Normal Brain ◽  
The Central Nervous System ◽  
Cellular Compartments ◽  
The Brain

Microglial cells are the resident macrophages in the central nervous system. These cells of mesodermal/mesenchymal origin migrate into all regions of the central nervous system, disseminate through the brain parenchyma, and acquire a specific ramified morphological phenotype termed “resting microglia.” Recent studies indicate that even in the normal brain, microglia have highly motile processes by which they scan their territorial domains. By a large number of signaling pathways they can communicate with macroglial cells and neurons and with cells of the immune system. Likewise, microglial cells express receptors classically described for brain-specific communication such as neurotransmitter receptors and those first discovered as immune cell-specific such as for cytokines. Microglial cells are considered the most susceptible sensors of brain pathology. Upon any detection of signs for brain lesions or nervous system dysfunction, microglial cells undergo a complex, multistage activation process that converts them into the “activated microglial cell.” This cell form has the capacity to release a large number of substances that can act detrimental or beneficial for the surrounding cells. Activated microglial cells can migrate to the site of injury, proliferate, and phagocytose cells and cellular compartments.

scholarly journals Neuroinflammatory responses of microglia in central nervous system trauma

2020 ◽  
Vol 40 (1_suppl) ◽  
pp. S25-S33
Author(s):  
Donald C Shields ◽  
Azizul Haque ◽  
Naren L Banik
Keyword(s):  
Central Nervous System ◽  
Nervous System ◽  
Microglial Activation ◽  
Immune Cell ◽  
Functional Restoration ◽  
Central Nervous System Trauma ◽  
The Central Nervous System ◽  
Inflammatory Phenotypes ◽  
Microglial Response ◽  
The Brain

Although relatively few in number compared to astrocytes and neurons, microglia demonstrate multiple, varied neuroimmunological functions in the central nervous system during normal and pathological states. After injury to the brain or spinal cord, microglia express beneficial pro- and anti-inflammatory phenotypes at various stages of recovery. However, prolonged microglial activation following injury has been linked to impaired parenchymal healing and functional restoration. The nature and magnitude of microglial response to injury relates in part to peripheral immune cell invasion, extent of tissue damage, and the local microenvironment.

scholarly journals Targeting CSF-1 ameliorates experimental autoimmune encephalomyelitis by depleting inflammatory monocytes and microglia in the central nervous system without affecting quiescent microglia

2020 ◽  
Author(s):  
Daniel Hwang ◽  
Larissa Lumi Watanabe Ishikawa ◽  
Alexandra Boehm ◽  
Ziver Sahin ◽  
Giacomo Casella ◽  
...  
Keyword(s):  
Central Nervous System ◽  
Nervous System ◽  
Experimental Autoimmune Encephalomyelitis ◽  
Myeloid Cells ◽  
Myeloid Cell ◽  
Autoimmune Encephalomyelitis ◽  
Inflammatory Monocytes ◽  
The Central Nervous System ◽  
Spleen And Lymph Nodes ◽  
Experimental Autoimmune

ABSTRACTMultiple sclerosis (MS) and its model, experimental autoimmune encephalomyelitis (EAE), are autoimmune diseases characterized by extensive infiltration of myeloid cells into the central nervous system (CNS). Although myeloid cells are essential to MS/EAE pathology, none of the current MS therapies specifically target them. A promising strategy for bridging this gap may be targeting the biological activity of CSF-1R, a receptor tyrosine kinase important for survival and functioning of certain myeloid cells, such as monocytes and macrophages. It has been shown that CSF-1R inhibitors suppress EAE, but it is not known whether targeting CSF-1R ligands, CSF-1 and IL-34, could be a viable therapeutic strategy. We found that neutralization of CSF-1 with Ab attenuates ongoing EAE, similar to CSF-1R inhibitor BLZ945, whereas neutralization of IL-34 had no effect. Both anti-CSF-1- and BLZ945-treated mice with EAE had greatly diminished numbers of monocyte-derived dendritic cells and microglia in the CNS. However, anti-CSF-1 antibody selectively depleted inflammatory microglia, whereas BLZ945 depleted virtually all microglia, including quiescent microglia. We also found depletion of myeloid cells in the spleen and lymph nodes of anti-CSF-1- and BLZ945-treated mice, but only a modest decrease in encephalitogenic T cell responses, suggesting that the depletion of CNS myeloid cells is more relevant to EAE suppression. Decreased myeloid cell populations in treated mice resulted in reduced production of IL-1β, a key inflammatory mediator in EAE. The treatments also reduced the frequencies of CCL2- and CCR2-expressing cells in the CNS, suggesting that CSF-1/CSF-1R inhibition may hinder recruitment of immune cells to the CNS. Our findings suggest that targeting CSF-1 may be effective in ameliorating myeloid cell-mediated MS pathology, while preserving homeostatic functions of microglia and decreasing risks that might arise from their ablation with small molecule inhibitors of CSF-1R.

Glucuronyl 3-sulfate occurs exclusively on distal unmyelinated terminals of selected sensory neurons in the peripheral nervous system

1995 ◽  
Vol 53 ◽  
pp. 958-959
Author(s):  
S.S. Spicer ◽  
B.A. Schulte
Keyword(s):  
Central Nervous System ◽  
Nervous System ◽  
Cerebral Cortex ◽  
Peripheral Nervous System ◽  
Sensory Neurons ◽  
Sensory Nerves ◽  
Tissue Antigens ◽  
The Central Nervous System ◽  
The Brain ◽  
Leu 7

Generation of monoclonal antibodies (MAbs) against tissue antigens has yielded several (VC1.1, HNK- 1, L2, 4F4 and anti-leu 7) which recognize the unique sugar epitope, glucuronyl 3-sulfate (Glc A3- SO4). In the central nervous system, these MAbs have demonstrated Glc A3-SO4 at the surface of neurons in the cerebral cortex, the cerebellum, the retina and other widespread regions of the brain.Here we describe the distribution of Glc A3-SO4 in the peripheral nervous system as determined by immunostaining with a MAb (VC 1.1) developed against antigen in the cat visual cortex. Outside the central nervous system, immunoreactivity was observed only in peripheral terminals of selected sensory nerves conducting transduction signals for touch, hearing, balance and taste. On the glassy membrane of the sinus hair in murine nasal skin, just deep to the ringwurt, VC 1.1 delineated an intensely stained, plaque-like area (Fig. 1). This previously unrecognized structure of the nasal vibrissae presumably serves as a tactile end organ and to our knowledge is not demonstrable by means other than its selective immunopositivity with VC1.1 and its appearance as a densely fibrillar area in H&E stained sections.

Central Nerve System Impairment, AMA Guides, Sixth Edition: An Overview

2018 ◽  
Vol 23 (1) ◽  
pp. 10-13
Author(s):  
James B. Talmage ◽  
Jay Blaisdell
Keyword(s):  
Spinal Cord ◽  
Central Nervous System ◽  
Nervous System ◽  
Neurological Impairment ◽  
Sixth Edition ◽  
Central Nerve System ◽  
The Central Nervous System ◽  
The One ◽  
Nerve System ◽  
The Brain

Abstract Injuries that affect the central nervous system (CNS) can be catastrophic because they involve the brain or spinal cord, and determining the underlying clinical cause of impairment is essential in using the AMA Guides to the Evaluation of Permanent Impairment (AMA Guides), in part because the AMA Guides addresses neurological impairment in several chapters. Unlike the musculoskeletal chapters, Chapter 13, The Central and Peripheral Nervous System, does not use grades, grade modifiers, and a net adjustment formula; rather the chapter uses an approach that is similar to that in prior editions of the AMA Guides. The following steps can be used to perform a CNS rating: 1) evaluate all four major categories of cerebral impairment, and choose the one that is most severe; 2) rate the single most severe cerebral impairment of the four major categories; 3) rate all other impairments that are due to neurogenic problems; and 4) combine the rating of the single most severe category of cerebral impairment with the ratings of all other impairments. Because some neurological dysfunctions are rated elsewhere in the AMA Guides, Sixth Edition, the evaluator may consult Table 13-1 to verify the appropriate chapter to use.

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