Blockade of CD127 Exerts a Dichotomous Clinical Effect in Marmoset Experimental Autoimmune Encephalomyelitis
In conclusion, promising clinical effect of CD127 blockade observed in a standard inbred/SPF mouse EAE model could only be partially replicated in an outbred/non-SPF non-human primate EAE model. Only in high responders to the immunization we found a positive response to the treatment. The mechanism underpinning this dichotomous response will be discussed. (Source: Journal of NeuroImmune Pharmacology)
Source: Journal of NeuroImmune Pharmacology - August 11, 2015 Category: Drugs & Pharmacology Source Type: research

Alterations in Spinal Cord Metabolism during Treatment of Neuropathic Pain
Abstract Therapeutic options for neuropathic pain have improved over the last 20 years yet still only provide partial relief with numerous side effects. Recently, metabolomics revealed that the concentration of the endogenous metabolite N,N-dimethylsphingosine (DMS) is increased in the spinal cord in a model of neuropathic pain. Additionally, it was shown that introduction of DMS to the central nervous system (CNS) resulted in mechanical allodynia. Here, we have examined two compounds; pregabalin (Lyrica®), a drug used to treat neuropathic pain, and N-oleoylethanolamine (NOE), an endogenous endocannabinoi...
Source: Journal of NeuroImmune Pharmacology - August 2, 2015 Category: Drugs & Pharmacology Source Type: research

The Role of Metabolomics in Brain Metabolism Research
Abstract This special edition of the Journal of Neuroimmune Pharmacology focuses on the leading edge of metabolomics in brain metabolism research. The topics covered include a metabolomic field overview and the challenges in neuroscience metabolomics. The workflow and utility of different analytical platforms to profile complex biological matrices that include biofluids, brain tissue and cells, are shown in several case studies. These studies demonstrate how global and targeted ...
Source: Journal of NeuroImmune Pharmacology - July 22, 2015 Category: Drugs & Pharmacology Source Type: research

ABCA1 is Necessary for Bexarotene-Mediated Clearance of Soluble Amyloid Beta from the Hippocampus of APP/PS1 Mice
Abstract Alzheimer’s disease (AD) is characterized by impaired clearance of amyloid beta (Aβ) peptides, leading to the accumulation of Aβ in the brain and subsequent neurodegeneration and cognitive impairment. ApoE plays a critical role in the proteolytic degradation of soluble forms of Aβ. This effect is dependent upon lipidation of ApoE by ABCA1-mediated transfer of phospholipids and cholesterol. ApoE and ABCA1 are induced by the action of the RXR agonist, bexarotene. We have previously shown that bexarotene reduces Aβ levels in AD mouse models and we have hypothesized that this effect ...
Source: Journal of NeuroImmune Pharmacology - July 15, 2015 Category: Drugs & Pharmacology Source Type: research

Adaptive Immunity in Schizophrenia: Functional Implications of T Cells in the Etiology, Course and Treatment
Abstract Schizophrenia is a severe and highly complex neurodevelopmental disorder with an unknown etiopathology. Recently, immunopathogenesis has emerged as one of the most compelling etiological models of schizophrenia. Over the past few years considerable research has been devoted to the role of innate immune responses in schizophrenia. The findings of such studies have helped to conceptualize schizophrenia as a chronic low-grade inflammatory disorder. Although the contribution of adaptive immune responses has also been emphasized, however, the precise role of T cells in the underlying neurobiological pathways o...
Source: Journal of NeuroImmune Pharmacology - July 11, 2015 Category: Drugs & Pharmacology Source Type: research

NMR-Based Metabolomics Separates the Distinct Stages of Disease in a Chronic Relapsing Model of Multiple Sclerosis
Abstract Relapsing experimental allergic encephalomyelitis (Cr-EAE) is commonly used to explore the pathogenesis and efficacy of new therapies for MS, but it is unclear whether the metabolome of Cr-EAE is comparable to human multiple sclerosis (MS). For MS, the diagnosis and staging can be achieved by metabolomics on blood using a combination of magnetic resonance spectroscopy and partial least squares discriminant analysis (PLS-DA). Here, we sought to discover whether this approach could be used to differentiate between sequential disease states in Cr-EAE and whether the same metabolites would be discriminatory. ...
Source: Journal of NeuroImmune Pharmacology - July 8, 2015 Category: Drugs & Pharmacology Source Type: research

CD4 + T Cells and Neuroprotection: Relevance to Motoneuron Injury and Disease
Abstract We have established a physiologically relevant mechanism of CD4+ T cell-mediated neuroprotection involving axotomized wildtype (WT) mouse facial motoneurons (FMN) with significance in the treatment of amyotrophic lateral sclerosis (ALS), a fatal MN disease. Use of the transgenic mouse model of ALS involving expression of human mutant superoxide dismutase genes (SOD1G93A; abbreviated here as mSOD1) has accelerated basic ALS research. Superimposition of facial nerve axotomy (FNA) on the mSOD1 mouse during pre-symptomatic stages indicates that they behave like immunodeficient mice in terms of increased FMN l...
Source: Journal of NeuroImmune Pharmacology - July 7, 2015 Category: Drugs & Pharmacology Source Type: research

Protective Effect of Lupeol Against Lipopolysaccharide-Induced Neuroinflammation via the p38/c-Jun N-Terminal Kinase Pathway in the Adult Mouse Brain
This study aimed to evaluate the effect of lupeol against lipopolysaccharide (LPS)-induced neuroinflammation in the cortex and hippocampus of adult mice. Our results showed that systemic administration of LPS induced glial cell production of proinflammatory cytokines, tumor necrosis factor (TNF)-α, inducible nitric oxide synthase (iNOS), and interleukin (IL)-1β, while co-treatment with lupeol significantly inhibited the LPS-induced activation of microglia and astrocytes, and decreased the LPS-induced generation of TNF-α, iNOS, and IL-1β. The intracellular mechanism involved in the LPS-induced activati...
Source: Journal of NeuroImmune Pharmacology - July 3, 2015 Category: Drugs & Pharmacology Source Type: research

An Act of Balance Between Adaptive and Maladaptive Immunity in Depression: a Role for T Lymphocytes
Abstract Historically the monoaminergic neurotransmitter system, in particular the serotonergic system, was seen as being responsible for the pathophysiology of major depressive disorder (MDD). With the advent of psychoneuroimmunology an important role of the immune system in the interface between the central nervous systems (CNS) and peripheral organ systems has emerged. In addition to the well-characterised neurobiological activities of cytokines, T cell function in the context of depression has been neglected so far. In this review we will investigate the biological roles of T cells in depression. Originally it...
Source: Journal of NeuroImmune Pharmacology - July 2, 2015 Category: Drugs & Pharmacology Source Type: research

Effects of Three Months Fingolimod Therapy on Heart Rate
Abstract Fingolimod is a novel disease-modifying drug for relapsing-remitting multiple sclerosis (RRMS). Fingolimod initiation associates with a decrease in heart rate (HR). However, the long-term effects of fingolimod on HR are not known. The aim of this study was prospectively investigate the effect of 3-month fingolimod therapy on HR. Twenty-seven RRMS patients underwent 24-h ambulatory electrocardiogram recording 20 ± 16 days before (baseline) and at the day of fingolimod initiation (1 day). Twenty-four patients completed 3 months follow-up (3 months). The average HR ov...
Source: Journal of NeuroImmune Pharmacology - June 20, 2015 Category: Drugs & Pharmacology Source Type: research

Turning Over a New Leaf: Cannabinoid and Endocannabinoid Modulation of Immune Function
Abstract Cannabis is a complex substance that harbors terpenoid-like compounds referred to as phytocannabinoids. The major psychoactive phytocannabinoid found in cannabis ∆9-tetrahydrocannabinol (THC) produces the majority of its pharmacological effects through two cannabinoid receptors, termed CB1 and CB2. The discovery of these receptors as linked functionally to distinct biological effects of THC, and the subsequent...
Source: Journal of NeuroImmune Pharmacology - June 9, 2015 Category: Drugs & Pharmacology Source Type: research

Apigenin, a Natural Flavonoid, Attenuates EAE Severity Through the Modulation of Dendritic Cell and Other Immune Cell Functions
Abstract Apigenin, a natural flavonoid, found in several plants, fruits, vegetables, herbs, and spices, is known to have anti-oxidant and anti-inflammatory properties that are evident in the use of these substances for centuries as medicinal approaches to treat asthma, insomnia, Parkinson’s disease, neuralgia, and shingles. However, there is a considerable dearth of information regarding its effect on immune cells, especially dendritic cells (DC) that maintain the critical balance between an immunogenic and tolerogenic immune response, in an immunospecialized location like the central nervous system (CNS). I...
Source: Journal of NeuroImmune Pharmacology - June 4, 2015 Category: Drugs & Pharmacology Source Type: research

Regulation of the Neurodegenerative Process Associated to Parkinson’s Disease by CD4+ T-cells
Abstract Neuroinflammation constitutes a fundamental process involved in the physiopathology of Parkinson’s disease (PD). Microglial cells play a central role in the outcome of neuroinflammation and consequent neurodegeneration of dopaminergic neurons in the substantia nigra. Current evidence indicates that CD4+ T-cells infiltrate the central nervous system (CNS) in PD, where they play a critical role determining the functional phenotype of microglia, thus regulating the progression of the neurodegenerative process. Here, we first analysed the pathogenic role of inflammatory phenotypes and the beneficial rol...
Source: Journal of NeuroImmune Pharmacology - May 28, 2015 Category: Drugs & Pharmacology Source Type: research

Pattern of CXCR7 Gene Expression in Mouse Brain Under Normal and Inflammatory Conditions
Abstract The chemokine stromal cell-derived factor-1 (SDF-1)/CXCL12 acting via its G-protein coupled receptor (GPCR) CXCR4 has been implicated in neurogenesis, neuromodulation, brain inflammation, HIV-1 encephalopathy and tumor growth. CXCR7 was identified as an alternate receptor for SDF-1/CXCL12. Characterization of CXCR7-deficient mice demonstrated a role for CXCR7 in fetal endothelial biology, cardiac development, and B-cell localization. Despite its ligand binding properties, CXCR7 does not seem to signal like a conventional GPCR. It has been suggested that CXCR7 may not function alone but in combination with...
Source: Journal of NeuroImmune Pharmacology - May 22, 2015 Category: Drugs & Pharmacology Source Type: research

A CB2-Selective Cannabinoid Suppresses T-Cell Activities and Increases Tregs and IL-10
Abstract We have previously shown that agonists selective for the cannabinoid receptor 2 (CB2), including O-1966, inhibit the Mixed Lymphocyte Reaction (MLR), an in vitro correlate of organ graft rejection, predominantly through effects on T-cells. Current studies explored the mechanism of this immunosuppression by O-1966 using mouse spleen cells. Treatment with O-1966 dose-relatedly decreased levels of the active nuclear forms of the transcription factors NF-κB and NFAT in wild-type T-cells, but not T-cells from CB2 knockout (CB2R k/o) mice. Additionally, a gene expression profile of purified T-cells from M...
Source: Journal of NeuroImmune Pharmacology - May 16, 2015 Category: Drugs & Pharmacology Source Type: research

T Cells—Protective or Pathogenic in Alzheimer’s Disease?
Abstract Alzheimer’s disease (AD) is the most common cause of dementia, and is characterised by deposits of amyloid β (Aβ), neurofibrillary tangles and neuronal loss. Neuroinflammatory changes have been identified as a feature of the disease, and recent studies have suggested a potential role for the peripheral immune system in driving these changes and, ultimately, the associated neuronal degeneration. A number of reports have detailed changes in the activation state and subtype of T cells in the circulation and CSF of AD patients and there is evidence of T cell infiltration into the brain. In thi...
Source: Journal of NeuroImmune Pharmacology - May 10, 2015 Category: Drugs & Pharmacology Source Type: research

Modulating the Immune Response Towards a Neuroregenerative Peri-injury Milieu After Cerebral Hemorrhage
Abstract Cerebral hemorrhages account for 15–20 % of stroke sub-types and have very poor prognoses. The mortality rate for cerebral hemorrhage patients is between 40 and 50 %, of which at least half of the deaths occur within the first 2 days, and 75 % of survivors are incapable of living independently after 1 year. Current emergency interventions involve lowering blood pressure and reducing intracranial pressure by controlled ventilations or, in the worst case scenarios, surgical intervention. Some hemostatic and coagulatherapeutic interventions are being investigated, although a fe...
Source: Journal of NeuroImmune Pharmacology - May 7, 2015 Category: Drugs & Pharmacology Source Type: research

Multiple Sclerosis and T Lymphocytes: An Entangled Story
Abstract Multiple sclerosis (MS) is the prototypic inflammatory disease of the central nervous system (CNS) characterized by multifocal areas of demyelination, axonal damage, activation of glial cells, and immune cell infiltration. Despite intensive years of research, the etiology of this neurological disorder remains elusive. Nevertheless, the abundance of immune cells such as T lymphocytes and their products in CNS lesions of MS patients supports the notion that MS is an immune-mediated disorder. An important body of evidence gathered from MS animal models such as experimental autoimmune encephalomyelitis (EAE),...
Source: Journal of NeuroImmune Pharmacology - May 7, 2015 Category: Drugs & Pharmacology Source Type: research

The Antitumor Activity of Plant-Derived Non-Psychoactive Cannabinoids
Abstract As a therapeutic agent, most people are familiar with the palliative effects of the primary psychoactive constituent of Cannabis sativa (CS), Δ9-tetrahydrocannabinol (THC), a molecule active at both the cannabinoid 1 (CB1) and cannabinoid 2 (CB2) receptor subtypes. Through the activation primarily of CB1 receptors in the central nervous system, THC can reduce nausea, emesis and pain in cancer patients undergoing chemotherapy. During the last decade, however, several studies have now shown that CB1 and CB2 receptor agonists can act as direct antitumor agents in a variety of aggressive cancers. In add...
Source: Journal of NeuroImmune Pharmacology - April 28, 2015 Category: Drugs & Pharmacology Source Type: research

Modulation of HIV GP120 Antigen-Specific Immune Responses In Vivo by Δ 9 -Tetrahydrocannabinol
Abstract Approximately 25 % of HIV patients use marijuana for its putative therapeutic benefit; however, it is unknown how cannabinoids affect the immune status of HIV patients. Previously, a surrogate in vitro mouse model was established, which induced CD8+ T cell proliferation and gp120-specific IFNγ production. ∆9-Tetrahydrocannabinol (THC), the predominant psychoactive compound in marijuana, suppressed or enhanced the responses depending on the magnitude of cellular activation. The purpose of the current study was to investigate whether THC produced similar effects in vivo and therefore a mouse mo...
Source: Journal of NeuroImmune Pharmacology - April 22, 2015 Category: Drugs & Pharmacology Source Type: research

The Effect of Central Nervous System Penetration Effectiveness of Highly Active Antiretroviral Therapy on Neuropsychological Performance and Neuroimaging in HIV Infected Individuals
Abstract The incidence of HIV-associated dementia has been greatly reduced in the era of highly active antiretroviral therapy (HAART); however milder forms of cognitive impairment persist. It remains uncertain whether HAART regimens with a high degree of central nervous system penetration effectiveness (CPE) exert beneficial neurological outcomes in HIV-infected (HIV+) individuals on stable treatment. Sixty-four HIV-infected adults on HAART were assigned a CPE score using a published ranking system and divided into high (≥7; n = 35) and low (
Source: Journal of NeuroImmune Pharmacology - April 22, 2015 Category: Drugs & Pharmacology Source Type: research

A Basal Tone of 2-Arachidonoylglycerol Contributes to Early Oligodendrocyte Progenitor Proliferation by Activating Phosphatidylinositol 3-Kinase (PI3K)/AKT and the Mammalian Target of Rapamycin (MTOR) Pathways
Abstract A basal tone of the endocannabinoid 2-arachidonoylglycerol (2-AG) enhances late oligodendrocyte progenitor cell (OPC) differentiation. Here, we investigated whether endogenous 2-AG may also promote OPC proliferation in earlier stages. We found that the blockade of 2-AG synthesizing enzymes, sn-1-diacylglycerol lipases α and β (DAGLs), with RHC-80267 or the antagonism of either CB1 or CB2 cannabinoid receptors with AM281 and AM630, respectively, impaired early OPC proliferation stimulated by platelet-derived growth factor (PDGF-AA) and basic fibroblast growth factor (bFGF). On the contrary, incr...
Source: Journal of NeuroImmune Pharmacology - April 22, 2015 Category: Drugs & Pharmacology Source Type: research

Effects of Cannabinoids on T-cell Function and Resistance to Infection
Abstract This review examines the effects of cannabinoids on immune function, with a focus on effects on T-cells, as well as on resistance to infection. The paper considers the immune modulating capacity of marijuana, of ∆9-THC extracted from the marijuana plant, and synthetic cannabinoids. Of particular interest are synthetic compounds that are CB2 receptor (CB2R) selective agonists. As the CB2R is principally expressed on cells of the immune system, agonists that target this receptor, and not CB1 (which is mainly expressed on neurons), have the possibility of altering immune function without psychoactive effec...
Source: Journal of NeuroImmune Pharmacology - April 15, 2015 Category: Drugs & Pharmacology Source Type: research

Psychiatric Symptoms, Salivary Cortisol and Cytokine Levels in Young Marijuana Users
Abstract Psychological maturation continues into young adulthood when substance abuse and several psychiatric disorders often emerge. Marijuana is the most common illicit drug abused by youths, typically preceding other illicit substances. We aimed to evaluate the complex and poorly studied relationships between marijuana use, psychiatric symptoms, and cortisol levels in young marijuana users. Psychiatric symptoms and salivary cortisol were measured in 122 youths (13–23 years old) with and without marijuana use. Psychiatric symptoms were evaluated using the Symptom-Checklist-90-R and Brief Psychiatric R...
Source: Journal of NeuroImmune Pharmacology - April 15, 2015 Category: Drugs & Pharmacology Source Type: research

Activation of the Macrophage α7 Nicotinic Acetylcholine Receptor and Control of Inflammation
Abstract Inflammatory responses to stimuli are essential body defenses against foreign threats. However, uncontrolled inflammation may result in serious health problems, which can be life-threatening. The α7 nicotinic acetylcholine receptor, a ligand-gated ion channel expressed in the nervous and immune systems, has an essential role in the control of inflammation. Activation of the macrophage α7 receptor by acetylcholine, nicotine, or other agonists, selectively inhibits production of pro-inflammatory cytokines while leaving anti-inflammatory cytokines undisturbed. The neural control of this regulatio...
Source: Journal of NeuroImmune Pharmacology - April 13, 2015 Category: Drugs & Pharmacology Source Type: research

The Complex Interaction Between Methamphetamine Abuse and HIV-1 Pathogenesis
Abstract The global HIV/AIDS pandemic has claimed the lives of an estimated 35 million people. A significant barrier for combating this global pandemic is substance use since it is associated with HIV transmission, delayed diagnosis/initiation of therapy, and poor adherence to therapy. Clinical studies also suggest a link between substance use and HIV-disease progression/AIDS-associated mortality. Methamphetamine (METH) use is one of the fastest-growing substance use problems in the world. METH use enhances high-risk sexual behaviors, therefore increases the likelihood of HIV-1 acquisition. METH use is also associ...
Source: Journal of NeuroImmune Pharmacology - April 8, 2015 Category: Drugs & Pharmacology Source Type: research

Dramatic Improvement of Chronic Inflammatory Demyelinating Polyneuropathy Through Tenofovir Treatment in a Patient Infected with Hepatitis B Virus
(Source: Journal of NeuroImmune Pharmacology)
Source: Journal of NeuroImmune Pharmacology - April 8, 2015 Category: Drugs & Pharmacology Source Type: research

Neurochemical Metabolomics Reveals Disruption to Sphingolipid Metabolism Following Chronic Haloperidol Administration
Abstract Haloperidol is an effective antipsychotic drug for treatment of schizophrenia, but prolonged use can lead to debilitating side effects. To better understand the effects of long-term administration, we measured global metabolic changes in mouse brain following 3 mg/kg/day haloperidol for 28 days. These conditions lead to movement-related side effects in mice akin to those observed in patients after prolonged use. Brain tissue was collected following microwave tissue fixation to arrest metabolism and extracted metabolites were assessed using both liquid and gas chromatography mass spectrometry (MS...
Source: Journal of NeuroImmune Pharmacology - April 7, 2015 Category: Drugs & Pharmacology Source Type: research

Changes in the endocannabinoid signaling system in CNS structures of TDP-43 transgenic mice: relevance for a neuroprotective therapy in TDP-43-related disorders
In conclusion, our data support the idea that the endocannabinoid signaling system, in particular the CB2 receptor, may serve for the development of a neuroprotective therapy in TDP-43-related disorders. We are presently engaged in pharmacological experiments to investigate this possibility. (Source: Journal of NeuroImmune Pharmacology)
Source: Journal of NeuroImmune Pharmacology - March 29, 2015 Category: Drugs & Pharmacology Source Type: research

Cannabinoids for the Treatment of Chronic Non-Cancer Pain: An Updated Systematic Review of Randomized Controlled Trials
Abstract An updated systematic review of randomized controlled trials examining cannabinoids in the treatment of chronic non-cancer pain was conducted according to PRISMA guidelines for systematic reviews reporting on health care outcomes. Eleven trials published since our last review met inclusion criteria. The quality of the trials was excellent. Seven of the trials demonstrated a significant analgesic effect. Several trials also demonstrated improvement in secondary outcomes (e.g., sleep, muscle stiffness and spasticity). Adverse effects most frequently reported such as fatigue and dizziness were mild to modera...
Source: Journal of NeuroImmune Pharmacology - March 21, 2015 Category: Drugs & Pharmacology Source Type: research

Behavioral, Metabolic, and Immune Consequences of Chronic Alcohol or Cannabinoids on HIV/AIDs: Studies in the Non-Human Primate SIV Model
Abstract HIV-associated mortality has been significantly reduced with antiretroviral therapy (ART), and HIV infection has become a chronic disease that frequently coexists with many disorders, including substance abuse (Azar et al. Drug Alcohol Depend 112:178–193, 2010; Phillips et al. J Gen Int Med 16:165, 2001). Alcohol and drugs of abuse may modify host-pathogen interactions at various levels including behavioral, metabolic, and immune consequences of HIV infection, as well as the ability of the virus to integrate into the genome and replicate in host cells. Identifying mechanisms responsible for these in...
Source: Journal of NeuroImmune Pharmacology - March 20, 2015 Category: Drugs & Pharmacology Source Type: research

Celastrol Ameliorates EAE Induction by Suppressing Pathogenic T Cell Responses in the Peripheral and Central Nervous Systems
Abstract Multiple sclerosis (MS) is the prototypical inflammatory demyelinating disease of the central nervous system (CNS), and MS results in physical and cognitive impairments, such as fatigue, pain, depression and bladder dysfunction. Though many therapies for MS have been developed, the safety profile and effectiveness of these therapies still need to be defined. Thus, new therapies for MS must be explored. Celastrol, a quinonemethide triterpene, is a pharmacologically active compound present in Thunder God Vine root extracts used to treat inflammatory and autoimmune diseases. Molecular studies have ident...
Source: Journal of NeuroImmune Pharmacology - March 14, 2015 Category: Drugs & Pharmacology Source Type: research

The 21st Annual Scientific Conference of the Society on NeuroImmune Pharmacology
(Source: Journal of NeuroImmune Pharmacology)
Source: Journal of NeuroImmune Pharmacology - March 12, 2015 Category: Drugs & Pharmacology Source Type: research

Increased Sensitivity to Cocaine Self-Administration in HIV-1 Transgenic Rats is Associated with Changes in Striatal Dopamine Transporter Binding
Abstract Cocaine abuse in HIV patients accelerates the progression and severity of neuropathology, motor impairment and cognitive dysfunction compared to non-drug using HIV patients. Cocaine and HIV interact with the dopamine transporter (DAT); however, the effect of their interaction on DAT binding remains understudied. The present study compared the dose–response functions for intravenous self-administration of cocaine and heroin between male HIV-1 transgenic (HIV-1 Tg) and Fischer 344 rats. The cocaine and heroin dose–response functions exhibit an inverted U-shape for both HIV-1 Tg and F344 rats. Fo...
Source: Journal of NeuroImmune Pharmacology - March 10, 2015 Category: Drugs & Pharmacology Source Type: research

Endocannabinoid Catabolic Enzymes Play Differential Roles in Thermal Homeostasis in Response to Environmental or Immune Challenge
Abstract Cannabinoid receptor agonists, such as Δ9-THC, the primary active constituent of Cannabis sativa, have anti-pyrogenic effects in a variety of assays. Recently, attention has turned to the endogenous cannabinoid system and how endocannabinoids, including 2-arachidonoylglycerol (2-AG) and anandamide, regulate multiple homeostatic processes, including thermoregulation. Inhibiting endocannabinoid catabolic enzymes, monoacylglycerol lipase (MAGL) or fatty acid amide hydrolase (FAAH), elevates levels of 2-AG or anandamide in vivo, respectively. The purpose of this experiment was to test the hypothesis tha...
Source: Journal of NeuroImmune Pharmacology - February 26, 2015 Category: Drugs & Pharmacology Source Type: research

Palmitoyl Serine: An Endogenous Neuroprotective Endocannabinoid-Like Entity After Traumatic Brain Injury
Abstract The endocannabinoid (eCB) system helps recovery following traumatic brain injury (TBI). Treatment with 2-arachidonoylglycerol (2-AG), a cerebral eCB ligand, was found to ameliorate the secondary damage. Interestingly, the fatty acid amino acid amide (FAAA) N-arachidonoyl-L-serine (AraS) exerts similar eCB dependent neuroprotective. The present study aimed to investigate the effects of the FAAA palmitoyl-serine (PalmS) following TBI. We utilized the TBI model in mice to examine the therapeutic potential of PalmS, injected 1 h following closed head injury (CHI). We followed the functional recovery of t...
Source: Journal of NeuroImmune Pharmacology - February 26, 2015 Category: Drugs & Pharmacology Source Type: research

Promoting global health—treatment and prevention of substance abuse and HIV in Asia
(Source: Journal of NeuroImmune Pharmacology)
Source: Journal of NeuroImmune Pharmacology - February 19, 2015 Category: Drugs & Pharmacology Source Type: research

Reciprocal Regulation of Substance P and IL-12/IL-23 and the Associated Cytokines, IFNγ/IL-17: A Perspective on the Relevance of This Interaction to Multiple Sclerosis
Abstract The neuropeptide substance P (SP) exhibits cytokine-like properties and exerts different effects in autoimmune inflammation. Various immune cells express SP and its neurokinin-1 receptor (NK1R) isoforms. A role for SP has been demonstrated in a number of autoimmune conditions, including multiple sclerosis (MS). In this work, we studied the role of SP and NK1R in human immune cells with a focus on their relationship with IL-12/IL-23 family cytokines and the associated IFN-γ/IL-17. AIMS: (1) To determine the role of SP mediated effects on induction of various inflammatory cytokines in peripheral blood...
Source: Journal of NeuroImmune Pharmacology - February 18, 2015 Category: Drugs & Pharmacology Source Type: research

Activation of Cannabinoid Type Two Receptors (CB 2 ) Diminish Inflammatory Responses in Macrophages and Brain Endothelium
In this study, we assessed by PCR array the expression of a wide range of genes increased in macrophages and BMVEC in inflammation. TNFα treatment upregulated 33 genes in primary human BMVEC, and two highly selective CB2 agonists diminished expression of 31 and 32 genes. These results were confirmed by functional assays (BBB protection after inflammatory insult and decreased migration of monocytes across BMVEC monolayers after CB2 stimulation). Similarly, CB2 stimulation in primary human macrophages led to the suppression of 35 genes out of the 50 genes upregulated by LPS. Such changes in gene expression paralleled d...
Source: Journal of NeuroImmune Pharmacology - February 11, 2015 Category: Drugs & Pharmacology Source Type: research

Exposure of Adolescent Mice to Delta-9-Tetrahydrocannabinol Induces Long-Lasting Modulation of Pro- and Anti-Inflammatory Cytokines in Hypothalamus and Hippocampus Similar to that Observed for Peripheral Macrophages
Abstract Cannabis use is frequent among adolescents. Its main component, delta-9-tetrahydrocannabinol (THC), affects the immune system. We recently demonstrated that chronic exposure of adolescent mice to THC suppressed immunity immediately after treatment but that after a washout period THC induced a long-lasting opposite modulation towards a proinflammatory and T-helper-1 phenotype in adulthood. The main objective of this study was to investigate whether the same effect was also present in brain regions such as the hypothalamus and hippocampus. Thirty-three-day-old adolescent and 80-day-old adult male...
Source: Journal of NeuroImmune Pharmacology - February 10, 2015 Category: Drugs & Pharmacology Source Type: research

Cerebellar Fastigial Nuclear Glutamatergic Neurons Regulate Immune Function via Hypothalamic and Sympathetic Pathways
Abstract We previously have shown that cerebellar fastigial nucleus (FN) modulates immune function, but pathways or mechanisms underlying this immunomodulation require clarification. Herein, an anterograde and retrograde tracing of nerve tracts between the cerebellar FN and hypothalamus/thalamus was performed in rats. After demonstrating a direct cerebellar FN-hypothalamic/thalamic glutamatergic projection, 6-diazo-5-oxo-L-norleucine (DON), an inhibitor of glutaminase that catalyzes glutamate synthesis, was injected bilaterally in the cerebellar FN and simultaneously, D,L-threo-β-hydroxyaspartic acid (THA), a...
Source: Journal of NeuroImmune Pharmacology - February 4, 2015 Category: Drugs & Pharmacology Source Type: research

The Choice of General Anesthetics May Not Affect Neuroinflammation and Impairment of Learning and Memory After Surgery in Elderly Rats
This study was to determine whether anesthetic choice (intravenous vs. volatile anesthetics) affects cognitive impairment and neuroinflammation in elderly rat. Total 54 twenty-month old male Fischer 344 rats were assigned randomly to control, right carotid exposure under propofol-buprenorphine or isoflurane-buprenorphine anesthesia groups. They were tested by Barnes maze and fear conditioning from 6 days after the surgery. Their brains were harvested 24 h after the surgery for quantifying interleukin (IL) 1β, tumor necrosis factor (TNF)α and ionized calcium binding adaptor molecule 1 (Iba-1). We showed...
Source: Journal of NeuroImmune Pharmacology - February 4, 2015 Category: Drugs & Pharmacology Source Type: research

Erythropoietin Delivered via Intra-Arterial Infusion Reduces Endoplasmic Reticulum Stress in Brain Microvessels of Rats Following Cerebral Ischemia and Reperfusion
Abstract Local infusion of low dose erythropoietin (EPO) alleviates cerebral ischemia and reperfusion (I/R) injury in rats; however, the underlying molecular mechanisms are still unclear. The present study investigated the effect of low dose EPO treatment on I/R-induced endoplasmic reticulum (ER) stress in brain tissue and isolated microvessels in rodents. Sprague-Dawley rats were subjected to 2 h ischemia/24 h reperfusion by middle cerebral artery (MCA) occlusion, then administered fluorescein isothiocyanate-labeled EPO via MCA infusion (MCAI) or subcutaneous injection (SI) to compare the efficiency of ...
Source: Journal of NeuroImmune Pharmacology - January 28, 2015 Category: Drugs & Pharmacology Source Type: research

Epigenetic Regulation of Immunological Alterations Following Prenatal Exposure to Marijuana Cannabinoids and its Long Term Consequences in Offspring
Abstract Use of marijuana during pregnancy is fairly commonplace and can be expected increase in frequency as more states legalize its recreational use. The cannabinoids present in marijuana have been shown to be immunosuppressive, yet the effect of prenatal exposure to cannabinoids on the immune system of the developing fetus, its long term consequences during adult stage of life, and transgenerational effects have not been well characterized. Confounding factors such as co-existing drug use make the impact of cannabis use on progeny inherently difficult to study in a human population. Data from various animal mo...
Source: Journal of NeuroImmune Pharmacology - January 25, 2015 Category: Drugs & Pharmacology Source Type: research

Nanomaterial Applications in Multiple Sclerosis Inflamed Brain
Abstract In the last years scientific progress in nanomaterials, where size and shape make the difference, has increased their utilization in medicine with the development of a promising new translational science: nanomedicine. Due to their surface and core biophysical properties, nanomaterials hold the promise for medical applications in central nervous system (CNS) diseases: inflammatory, degenerative and tumors. The present review is focused on nanomaterials at the neuro-immune interface, evaluating two aspects: the possible CNS inflammatory response induced by nanomaterials and the developments of nanomaterial...
Source: Journal of NeuroImmune Pharmacology - January 24, 2015 Category: Drugs & Pharmacology Source Type: research

Metabolic Profiling and Phenotyping of Central Nervous System Diseases: Metabolites Bring Insights into Brain Dysfunctions
Abstract Metabolic phenotyping corresponds to the large-scale quantitative and qualitative analysis of the metabolome i.e., the low-molecular weight
Source: Journal of NeuroImmune Pharmacology - January 24, 2015 Category: Drugs & Pharmacology Source Type: research

Exposure to Δ9-Tetrahydrocannabinol Impairs the Differentiation of Human Monocyte-derived Dendritic Cells and their Capacity for T cell Activation
Abstract The capacity for human monocytes to differentiate into antigen-presenting dendritic cells (DC) can be influenced by a number of immune modulating signals. Monocytes express intracellular cannabinoid type 1 (CB1) and 2 (CB2) receptors and we demonstrate that exposure to Δ9-tetrahydrocannabinol (THC) inhibits the forskolin-induced generation of cyclic adenosine monophosphate in a CB2-specific manner. In order to examine the potential impact of cannabinoids on the generation of monocyte-derived DC, monocytes were cultured in vitro with differentiation medium alone [containing granulocyte/macrophage-col...
Source: Journal of NeuroImmune Pharmacology - January 23, 2015 Category: Drugs & Pharmacology Source Type: research

Mutations at Tyrosine 88, Lysine 92 and Tyrosine 470 of Human Dopamine Transporter Result in an Attenuation of HIV-1 Tat-Induced Inhibition of Dopamine Transport
Abstract HIV-1 transactivator of transcription (Tat) protein disrupts the dopamine (DA) neurotransmission by inhibiting DA transporter (DAT) function, leading to increased neurocognitive impairment in HIV-1 infected individuals. Through integrated computational modeling and pharmacological studies, we have demonstrated that mutation of tyrosine470 (Y470H) of human DAT (hDAT) attenuates Tat-induced inhibition of DA uptake by changing the transporter conformational transitions. The present study examined the functional influences of other substitutions at tyrosine470 (Y470F and Y470A) and tyrosine88 (Y88F) and lysin...
Source: Journal of NeuroImmune Pharmacology - January 22, 2015 Category: Drugs & Pharmacology Source Type: research

Nanotherapeutic Approach for Opiate Addiction Using DARPP-32 Gene Silencing in an Animal Model of Opiate Addiction
Abstract Opiates act on the dopaminergic system of the brain and perturb 32 kDa dopamine and adenosine 3′, 5′-monophosphate-regulated phosphoprotein (DARPP-32) function. The DARPP-32 mediated inhibition of protein phosphatase-1 (PP-1) and modulation of transcriptional factor CREB is critical to the changes in neuronal plasticity that result in behavioral responses during drug abuse. To investigate the role of DARPP-32 mediated signaling on withdrawal behavior in a rat model of opiate addiction, we used intracerebral administration of gold nanorods (GNR) complexed to DARPP-32 siRNA to silence DARPP...
Source: Journal of NeuroImmune Pharmacology - January 22, 2015 Category: Drugs & Pharmacology Source Type: research

Cannabinoid Signaling and Neuroinflammatory Diseases: A Melting pot for the Regulation of Brain Immune Responses
Abstract The concept of the central nervous system (CNS) as an immune-privileged site, essentially due to the presence of the blood brain barrier, appears to be overly simplistic. Indeed, within healthy CNS immune activities are permitted and are required for neuronal function and host defense, not only due to the presence of the resident innate immune cells of the brain, but also by virtue of a complex cross-talk of the CNS with peripheral immune cells. Nonetheless, long-standing and persisting neuroinflammatory responses are most often detrimental and characterize several neuroinflammatory diseases, including mu...
Source: Journal of NeuroImmune Pharmacology - January 20, 2015 Category: Drugs & Pharmacology Source Type: research