Submit to Brain Sciences Review for Brain Sciences Propose a Special Issue

Journal Menu

Journal Browser

► Journal Browser

Advances in Neuroimmunology

Print Special Issue Flyer
Special Issue Editors
Special Issue Information
Keywords
Benefits of Publishing in a Special Issue
Published Papers

A special issue of Brain Sciences (ISSN 2076-3425).

Deadline for manuscript submissions: closed (1 April 2016) | Viewed by 87900

Printed Edition Available!
A printed edition of this Special Issue is available here.

Special issue Advances in Neuroimmunology book cover image

Share This Special Issue

Special Issue Editor

Prof. Dr. Donna Gruol

E-Mail Website
Guest Editor

Neuroscience Department, The Scripps Research Institute, 10550 North Torrey Pines Road, La Jolla, CA 92037, USA
Interests: neuroimmune actions on the brain; alcohol/neuroimmune interactions; synaptic transmission; neurophysiology; calcium imaging
Special Issues, Collections and Topics in MDPI journals

Special Issue Information

Dear Colleagues,

Neuroimmunity is a relative new and rapidly expanding area of interest that critically impacts normal brain function and a wide range of neurological disorders. Neuroimmune mechanisms operate within the nervous system and between the nervous system and periphery. Glial cells of the nervous system play a primary role in neuroimmunity, through their ability to produce and respond to neuroimmune signaling factors, which serve a number of functions, such as homeostatic regulation of nervous system function and defense against insult and infection. Dysfunction of the neuroimmune system is now thought to be an important contributing factor to many disease and injury states.

The purpose of this Special Issue is to provide a representative view of current research in this growing field, with an emphasis on the central nervous system.

Prof. Dr. Donna Gruol
Guest Editor

Manuscript Submission Information

Manuscripts should be submitted online at www.mdpi.com by registering and logging in to this website. Once you are registered, click here to go to the submission form. Manuscripts can be submitted until the deadline. All submissions that pass pre-check are peer-reviewed. Accepted papers will be published continuously in the journal (as soon as accepted) and will be listed together on the special issue website. Research articles, review articles as well as short communications are invited. For planned papers, a title and short abstract (about 100 words) can be sent to the Editorial Office for announcement on this website.

Submitted manuscripts should not have been published previously, nor be under consideration for publication elsewhere (except conference proceedings papers). All manuscripts are thoroughly refereed through a single-blind peer-review process. A guide for authors and other relevant information for submission of manuscripts is available on the Instructions for Authors page. Brain Sciences is an international peer-reviewed open access monthly journal published by MDPI.

Please visit the Instructions for Authors page before submitting a manuscript. The Article Processing Charge (APC) for publication in this open access journal is 2200 CHF (Swiss Francs). Submitted papers should be well formatted and use good English. Authors may use MDPI's English editing service prior to publication or during author revisions.

Keywords

neuroimmune
cytokine
chemokine
glia cell
neuron
neurodevelopment
neuroimmune disorder
neurologic disease
psychiatric disease
neuronal injury

Benefits of Publishing in a Special Issue

Ease of navigation: Grouping papers by topic helps scholars navigate broad scope journals more efficiently.
Greater discoverability: Special Issues support the reach and impact of scientific research. Articles in Special Issues are more discoverable and cited more frequently.
Expansion of research network: Special Issues facilitate connections among authors, fostering scientific collaborations.
External promotion: Articles in Special Issues are often promoted through the journal's social media, increasing their visibility.
e-Book format: Special Issues with more than 10 articles can be published as dedicated e-books, ensuring wide and rapid dissemination.

Further information on MDPI's Special Issue polices can be found here.

Published Papers (11 papers)

Download All Papers

Order results

Result details

Show export options Show export options

Select all

Export citation of selected articles as:

Editorial

Jump to: Research, Review

153 KiB

Open AccessEditorial

Advances in Neuroimmunology

by Donna Gruol

Brain Sci. 2017, 7(10), 124; https://doi.org/10.3390/brainsci7100124 - 27 Sep 2017

Cited by 3 | Viewed by 4357

Abstract

It is now widely accepted that an innate immune system exists within the brain and plays an important role in both physiological and pathological processes [1,2].[...] Full article

(This article belongs to the Special Issue Advances in Neuroimmunology)

Research

Jump to: Editorial, Review

5643 KiB

Open AccessArticle

NLRP12 Inflammasome Expression in the Rat Brain in Response to LPS during Morphine Tolerance

by Sulie L. Chang, Wenfei Huang, Xin Mao and Sabroni Sarkar

Brain Sci. 2017, 7(2), 14; https://doi.org/10.3390/brainsci7020014 - 6 Feb 2017

Cited by 11 | Viewed by 5938

Abstract

Morphine, an effective but addictive analgesic, can profoundly affect the inflammatory response to pathogens, and long-term use can result in morphine tolerance. Inflammasomes are protein complexes involved in the inflammatory response. The nucleotide-binding oligomerization domain-like receptor (NLR) Family Pyrin Domain Containing (NLRP) 12 (NLRP12) inflammasome has been reported to have anti-inflammatory activity. In this study, we examined the expression of NLRP12 inflammasome related genes in the adult F344 rat brain in response to the bacterial endotoxin lipopolysaccharide (LPS) in the presence and absence of morphine tolerance. Morphine tolerance was elicited using the 2 + 4 morphine-pelleting protocol. On Day 1, the rats were pelleted subcutaneously with 2 pellets of morphine (75 mg/pellet) or a placebo; on Days 2 and 4 pellets were given. On Day 5, the animals were randomly assigned to receive either 250 µg/kg LPS or saline (i.p.). The expression of 84 inflammasome related genes in the rat brain was examined using a Ploymerase Chain Reaction (PCR) array. In response to LPS, there was a significant increase in the expression of the pro-inflammatory cytokine/chemokine genes interleukin-1 beta (Il-1β), interleukin-6 (Il-6), C-C motif chemokine ligand 2 (Ccl2), C-C motif chemokine ligand 7 (Ccl7), C-X-C motif chemokine ligand 1 (Cxcl1), and C-X-C motif chemokine ligand 3 (Cxcl3) and a significant decrease in the anti-inflammatory NLRP12 gene in both morphine-tolerant and placebo-control rats compared to saline-treated rats, although the changes were greater in the placebo-control animals. The Library of Integrated Network-Based Cellular Signatures’ (LINCS) connectivity map was used to analyze the list of affected genes to identify potential targets associated with the interactions of LPS and morphine tolerance. Our data indicate that, in the morphine tolerant state, the expression of NLRP12 and its related genes is altered in response to LPS and that the Vacuolar protein-sorting-associated protein 28 (VPS28), which is involved in the transport and sorting of proteins into sub-cellular vesicles, may be the key regulator of these alterations. Full article

(This article belongs to the Special Issue Advances in Neuroimmunology)

► Show Figures

Figure 1

1155 KiB

Open AccessArticle

Stress and Withdrawal from Chronic Ethanol Induce Selective Changes in Neuroimmune mRNAs in Differing Brain Sites

by Darin J. Knapp, Kathryn M. Harper, Buddy A. Whitman, Zachary Zimomra and George R. Breese

Brain Sci. 2016, 6(3), 25; https://doi.org/10.3390/brainsci6030025 - 27 Jul 2016

Cited by 37 | Viewed by 5903

Abstract

Stress is a strong risk factor in alcoholic relapse and may exert effects that mimic aspects of chronic alcohol exposure on neurobiological systems. With the neuroimmune system becoming a prominent focus in the study of the neurobiological consequences of stress, as well as chronic alcohol exposure proving to be a valuable focus in this regard, the present study sought to compare the effects of stress and chronic ethanol exposure on induction of components of the neuroimmune system. Rats were exposed to either 1 h exposure to a mild stressor (restraint) or exposure to withdrawal from 15 days of chronic alcohol exposure (i.e., withdrawal from chronic ethanol, WCE) and assessed for neuroimmune mRNAs in brain. Restraint stress alone elevated chemokine (C–C motif) ligand 2 (CCL2), interleukin-1-beta (IL-1β), tumor necrosis factor alpha (TNFα) and toll-like receptor 4 (TLR4) mRNAs in the cerebral cortex within 4 h with a return to a control level by 24 h. These increases were not accompanied by an increase in corresponding proteins. Withdrawal from WCE also elevated cytokines, but did so to varying degrees across different cytokines and brain regions. In the cortex, stress and WCE induced CCL2, TNFα, IL-1β, and TLR4 mRNAs. In the hypothalamus, only WCE induced cytokines (CCL2 and IL-1β) while in the hippocampus, WCE strongly induced CCL2 while stress and WCE induced IL-1β. In the amygdala, only WCE induced CCL2. Finally—based on the previously demonstrated role of corticotropin-releasing factor 1 (CRF1) receptor inhibition in blocking WCE-induced cytokine mRNAs—the CRF1 receptor antagonist CP154,526 was administered to a subgroup of stressed rats and found to be inactive against induction of CCL2, TNFα, or IL-1β mRNAs. These differential results suggest that stress and WCE manifest broad neuroimmune effects in brain depending on the cytokine and brain region, and that CRF inhibition may not be a relevant mechanism in non-alcohol exposed animals. Overall, these effects are complex in terms of their neuroimmune targets and neuroanatomical specificity. Further investigation of the differential distribution of cytokine induction across neuroanatomical regions, individual cell types (e.g., neuronal phenotypes and glia), severity of chronic alcohol exposure, as well as across differing stress types may prove useful in understanding differential mechanisms of induction and for targeting select systems for pharmacotherapeutic intervention in alcoholism. Full article

(This article belongs to the Special Issue Advances in Neuroimmunology)

► Show Figures

Graphical abstract

442 KiB

Open AccessArticle

Neuroimmunology of the Interleukins 13 and 4

by Simone Mori, Pamela Maher and Bruno Conti

Brain Sci. 2016, 6(2), 18; https://doi.org/10.3390/brainsci6020018 - 13 Jun 2016

Cited by 82 | Viewed by 9236

Abstract

The cytokines interleukin 13 and 4 share a common heterodimeric receptor and are important modulators of peripheral allergic reactions. Produced primarily by T-helper type 2 lymphocytes, they are typically considered as anti-inflammatory cytokines because they can downregulate the synthesis of T-helper type 1 pro-inflammatory cytokines. Their presence and role in the brain is only beginning to be investigated and the data collected so far shows that these molecules can be produced by microglial cells and possibly by neurons. Attention has so far been given to the possible role of these molecules in neurodegeneration. Both neuroprotective or neurotoxic effects have been proposed based on evidence that interleukin 13 and 4 can reduce inflammation by promoting the M2 microglia phenotype and contributing to the death of microglia M1 phenotype, or by potentiating the effects of oxidative stress on neurons during neuro-inflammation. Remarkably, the heterodimeric subunit IL-13Rα1 of their common receptor was recently demonstrated in dopaminergic neurons of the ventral tegmental area and the substantia nigra pars compacta, suggesting the possibility that both cytokines may affect the activity of these neurons regulating reward, mood, and motor coordination. In mice and man, the gene encoding for IL-13Rα1 is expressed on the X chromosome within the PARK12 region of susceptibility to Parkinson’s disease (PD). This, together with finding that IL-13Rα1 contributes to loss of dopaminergic neurons during inflammation, indicates the possibility that these cytokines may contribute to the etiology or the progression of PD. Full article

(This article belongs to the Special Issue Advances in Neuroimmunology)

► Show Figures

Graphical abstract

3460 KiB

Open AccessArticle

Prior Binge Ethanol Exposure Potentiates the Microglial Response in a Model of Alcohol-Induced Neurodegeneration

by Simon Alex Marshall, Chelsea Rhea Geil and Kimberly Nixon

Brain Sci. 2016, 6(2), 16; https://doi.org/10.3390/brainsci6020016 - 26 May 2016

Cited by 84 | Viewed by 8372

Abstract

Excessive alcohol consumption results in neurodegeneration which some hypothesize is caused by neuroinflammation. One characteristic of neuroinflammation is microglial activation, but it is now well accepted that microglial activation may be pro- or anti-inflammatory. Recent work indicates that the Majchrowicz model of alcohol-induced neurodegeneration results in anti-inflammatory microglia, while intermittent exposure models with lower doses and blood alcohol levels produce microglia with a pro-inflammatory phenotype. To determine the effect of a repeated binge alcohol exposure, rats received two cycles of the four-day Majchrowicz model. One hemisphere was then used to assess microglia via immunohistochemistry and while the other was used for ELISAs of cytokines and growth factors. A single binge ethanol exposure resulted in low-level of microglial activation; however, a second binge potentiated the microglial response. Specifically, double binge rats had greater OX-42 immunoreactivity, increased ionized calcium-binding adapter molecule 1 (Iba-1+) cells, and upregulated tumor necrosis factor-α (TNF-α) compared with the single binge ethanol group. These data indicate that prior ethanol exposure potentiates a subsequent microglia response, which suggests that the initial exposure to alcohol primes microglia. In summary, repeated ethanol exposure, independent of other immune modulatory events, potentiates microglial activity. Full article

(This article belongs to the Special Issue Advances in Neuroimmunology)

► Show Figures

Graphical abstract

3026 KiB

Open AccessArticle

Astrocytic IL-6 Influences the Clinical Symptoms of EAE in Mice

by Maria Erta, Mercedes Giralt, Silvia Jiménez, Amalia Molinero, Gemma Comes and Juan Hidalgo

Brain Sci. 2016, 6(2), 15; https://doi.org/10.3390/brainsci6020015 - 17 May 2016

Cited by 22 | Viewed by 6492

Abstract

Interleukin-6 (IL-6) is a multifunctional cytokine that not only plays major roles in the immune system, but also serves as a coordinator between the nervous and endocrine systems. IL-6 is produced in multiple cell types in the CNS, and in turn, many cells respond to it. It is therefore important to ascertain which cell type is the key responder to IL-6 during both physiological and pathological conditions. In order to test the role of astrocytic IL-6 in neuroinflammation, we studied an extensively-used animal model of multiple sclerosis, experimental autoimmune encephalomyelitis (EAE), in mice with an IL-6 deficiency in astrocytes (Ast-IL-6 KO). Results indicate that lack of astrocytic IL-6 did not cause major changes in EAE symptomatology. However, a delay in the onset of clinical signs was observed in Ast-IL-6 KO females, with fewer inflammatory infiltrates and decreased demyelination and some alterations in gliosis and vasogenesis, compared to floxed mice. These results suggest that astrocyte-secreted IL-6 has some roles in EAE pathogenesis, at least in females. Full article

(This article belongs to the Special Issue Advances in Neuroimmunology)

► Show Figures

Graphical abstract

Review

Jump to: Editorial, Research

273 KiB

Open AccessReview

Overview of Traumatic Brain Injury: An Immunological Context

by Damir Nizamutdinov and Lee A. Shapiro

Brain Sci. 2017, 7(1), 11; https://doi.org/10.3390/brainsci7010011 - 23 Jan 2017

Cited by 78 | Viewed by 9432

Abstract

Traumatic brain injury (TBI) afflicts people of all ages and genders, and the severity of injury ranges from concussion/mild TBI to severe TBI. Across all spectrums, TBI has wide-ranging, and variable symptomology and outcomes. Treatment options are lacking for the early neuropathology associated with TBIs and for the chronic neuropathological and neurobehavioral deficits. Inflammation and neuroinflammation appear to be major mediators of TBI outcomes. These systems are being intensively studies using animal models and human translational studies, in the hopes of understanding the mechanisms of TBI, and developing therapeutic strategies to improve the outcomes of the millions of people impacted by TBIs each year. This manuscript provides an overview of the epidemiology and outcomes of TBI, and presents data obtained from animal and human studies focusing on an inflammatory and immunological context. Such a context is timely, as recent studies blur the traditional understanding of an “immune-privileged” central nervous system. In presenting the evidence for specific, adaptive immune response after TBI, it is hoped that future studies will be interpreted using a broader perspective that includes the contributions of the peripheral immune system, to central nervous system disorders, notably TBI and post-traumatic syndromes. Full article

(This article belongs to the Special Issue Advances in Neuroimmunology)

587 KiB

Open AccessReview

Immunomodulators as Therapeutic Agents in Mitigating the Progression of Parkinson’s Disease

by Bethany Grimmig, Josh Morganti, Kevin Nash and Paula C Bickford

Brain Sci. 2016, 6(4), 41; https://doi.org/10.3390/brainsci6040041 - 23 Sep 2016

Cited by 20 | Viewed by 6234

Abstract

Parkinson’s disease (PD) is a common neurodegenerative disorder that primarily afflicts the elderly. It is characterized by motor dysfunction due to extensive neuron loss in the substantia nigra pars compacta. There are multiple biological processes that are negatively impacted during the pathogenesis of PD, and are implicated in the cell death in this region. Neuroinflammation is evidently involved in PD pathology and mitigating the inflammatory cascade has been a therapeutic strategy. Age is the number one risk factor for PD and thus needs to be considered in the context of disease pathology. Here, we discuss the role of neuroinflammation within the context of aging as it applies to the development of PD, and the potential for two representative compounds, fractalkine and astaxanthin, to attenuate the pathophysiology that modulates neurodegeneration that occurs in Parkinson’s disease. Full article

(This article belongs to the Special Issue Advances in Neuroimmunology)

► Show Figures

Figure 1

242 KiB

Open AccessReview

Oligodendrocyte Injury and Pathogenesis of HIV-1-Associated Neurocognitive Disorders

by Han Liu, Enquan Xu, Jianuo Liu and Huangui Xiong

Brain Sci. 2016, 6(3), 23; https://doi.org/10.3390/brainsci6030023 - 22 Jul 2016

Cited by 21 | Viewed by 5862

Abstract

Oligodendrocytes wrap neuronal axons to form myelin, an insulating sheath which is essential for nervous impulse conduction along axons. Axonal myelination is highly regulated by neuronal and astrocytic signals and the maintenance of myelin sheaths is a very complex process. Oligodendrocyte damage can cause axonal demyelination and neuronal injury, leading to neurological disorders. Demyelination in the cerebrum may produce cognitive impairment in a variety of neurological disorders, including human immunodeficiency virus type one (HIV-1)-associated neurocognitive disorders (HAND). Although the combined antiretroviral therapy has markedly reduced the incidence of HIV-1-associated dementia, a severe form of HAND, milder forms of HAND remain prevalent even when the peripheral viral load is well controlled. HAND manifests as a subcortical dementia with damage in the brain white matter (e.g., corpus callosum), which consists of myelinated axonal fibers. How HIV-1 brain infection causes myelin injury and resultant white matter damage is an interesting area of current HIV research. In this review, we tentatively address recent progress on oligodendrocyte dysregulation and HAND pathogenesis. Full article

(This article belongs to the Special Issue Advances in Neuroimmunology)

► Show Figures

Graphical abstract

2015 KiB

Open AccessFeature PaperReview

Impact of Increased Astrocyte Expression of IL-6, CCL2 or CXCL10 in Transgenic Mice on Hippocampal Synaptic Function

by Donna L. Gruol

Brain Sci. 2016, 6(2), 19; https://doi.org/10.3390/brainsci6020019 - 17 Jun 2016

Cited by 25 | Viewed by 6787

Abstract

An important aspect of CNS disease and injury is the elevated expression of neuroimmune factors. These factors are thought to contribute to processes ranging from recovery and repair to pathology. The complexity of the CNS and the multitude of neuroimmune factors that are expressed in the CNS during disease and injury is a challenge to an understanding of the consequences of the elevated expression relative to CNS function. One approach to address this issue is the use of transgenic mice that express elevated levels of a specific neuroimmune factor in the CNS by a cell type that normally produces it. This approach can provide basic information about the actions of specific neuroimmune factors and can contribute to an understanding of more complex conditions when multiple neuroimmune factors are expressed. This review summarizes studies using transgenic mice that express elevated levels of IL-6, CCL2 or CXCL10 through increased astrocyte expression. The studies focus on the effects of these neuroimmune factors on synaptic function at the Schaffer collateral to CA1 pyramidal neuron synapse of the hippocampus, a brain region that plays a key role in cognitive function. Full article

(This article belongs to the Special Issue Advances in Neuroimmunology)

► Show Figures

Figure 1

2264 KiB

Open AccessFeature PaperReview

The Effects of Hypoxia and Inflammation on Synaptic Signaling in the CNS

by Gatambwa Mukandala, Ronan Tynan, Sinead Lanigan and John J. O’Connor

Brain Sci. 2016, 6(1), 6; https://doi.org/10.3390/brainsci6010006 - 17 Feb 2016

Cited by 103 | Viewed by 17887

Abstract

Normal brain function is highly dependent on oxygen and nutrient supply and when the demand for oxygen exceeds its supply, hypoxia is induced. Acute episodes of hypoxia may cause a depression in synaptic activity in many brain regions, whilst prolonged exposure to hypoxia leads to neuronal cell loss and death. Acute inadequate oxygen supply may cause anaerobic metabolism and increased respiration in an attempt to increase oxygen intake whilst chronic hypoxia may give rise to angiogenesis and erythropoiesis in order to promote oxygen delivery to peripheral tissues. The effects of hypoxia on neuronal tissue are exacerbated by the release of many inflammatory agents from glia and neuronal cells. Cytokines, such as TNF-α, and IL-1β are known to be released during the early stages of hypoxia, causing either local or systemic inflammation, which can result in cell death. Another growing body of evidence suggests that inflammation can result in neuroprotection, such as preconditioning to cerebral ischemia, causing ischemic tolerance. In the following review we discuss the effects of acute and chronic hypoxia and the release of pro-inflammatory cytokines on synaptic transmission and plasticity in the central nervous system. Specifically we discuss the effects of the pro-inflammatory agent TNF-α during a hypoxic event. Full article

(This article belongs to the Special Issue Advances in Neuroimmunology)

► Show Figures

Journal Menu

Journal Browser

Advances in Neuroimmunology

Share This Special Issue

Special Issue Editor

Special Issue Information

Keywords

Benefits of Publishing in a Special Issue

Published Papers (11 papers)

Editorial

Research

Review

Further Information

Guidelines

MDPI Initiatives

Follow MDPI