Dopamine Increases CD14 + CD16 + Monocyte Transmigration across the Blood Brain Barrier: Implications for Substance Abuse and HIV Neuropathogenesis
AbstractIn human immunodeficiency virus-1 (HIV) infected individuals, substance abuse may accelerate the development and/or increase the severity of HIV associated neurocognitive disorders (HAND). It is proposed that CD14+CD16+ monocytes mediate HIV entry into the central nervous system (CNS) and that uninfected and infected CD14+CD16+ monocyte transmigration across the blood brain barrier (BBB) contributes to the establishment and propagation of CNS HIV viral reservoirs and chronic neuroinflammation, important factors in the development of HAND. The effects of substance abuse on the frequency of CD14+CD16+ monocytes in th...
Source: Journal of NeuroImmune Pharmacology - January 29, 2017 Category: Drugs & Pharmacology Source Type: research

Galectin-1 Reduces Neuroinflammation via Modulation of Nitric Oxide-Arginase Signaling in HIV-1 Transfected Microglia: a Gold Nanoparticle-Galectin-1 “Nanoplex” a Possible Neurotherapeutic?
AbstractGalectins are a family of β-galactoside-binding lectins that are important modulators of homeostasis in the central nervous system (CNS). Galectin-1 is a pivotal regulator of microglia activation that alters the immune balance from neurodegeneration to neuroprotection and could have therapeutic relevance in HIV associated n eurocognitive disorders (HAND). We have previously shown that galectin-1 treatment decreased oxidative stress in microglia and hypothesize that the mechanism underlying this phenomenon is the cross regulatory interactions between Nitric oxide (NO) and Arginase I activity in microglia. We in...
Source: Journal of NeuroImmune Pharmacology - December 27, 2016 Category: Drugs & Pharmacology Source Type: research

Safety and Efficacy of Anti-Amyloid- β Immunotherapy in Alzheimer’s Disease: A Systematic Review and Meta-Analysis
AbstractImmunotherapeutics targeting amyloid- β (Aβ) have had mixed results in clinical trials. The present study aims to evaluate the safety and clinical efficacy of immunotherapeutic agents targeting Aβ in Alzheimer’s disease. Randomised controlled trials of at least two weeks duration were included in the review. Fourteen randomised con trolled trials (n = 5554) were identified in a systematic search of eight electronic databases. Upon pooling of data, there was no increased risk of any adverse event, serious adverse events, or death with the exception of a near fivefold increase in amyloi...
Source: Journal of NeuroImmune Pharmacology - December 26, 2016 Category: Drugs & Pharmacology Source Type: research

HIV-1 Glycoprotein 120 Enhancement of N-Methyl-D-Aspartate NMDA Receptor-Mediated Excitatory Postsynaptic Currents: Implications for HIV-1-Associated Neural Injury
AbstractIt is widely accepted that human immunodeficiency virus type 1 (HIV-1) envelope glycoprotein 120 (gp120) plays an important role in HIV-1-induced neural injury and pathogenesis of HIV-1-associated dementia (HAND). Multiple pathways have been proposed for gp120-induced neurotoxicity, amongst is the activation of N-Methyl-D-Aspartate receptors (NMDARs). It has been shown that gp120 causes neuronal injury or death and gp120 transgenic mice exhibit neurological similarity to that of HAND, all of which can be blocked or attenuated by NMDAR antagonists. Several lines of evidence indicate the subtype and location of activ...
Source: Journal of NeuroImmune Pharmacology - December 22, 2016 Category: Drugs & Pharmacology Source Type: research

Vitamin D Treatment Attenuates Neuroinflammation and Dopaminergic Neurodegeneration in an Animal Model of Parkinson ’s Disease, Shifting M1 to M2 Microglia Responses
AbstractMicroglia-mediated neuroinflammation has been described as a common hallmark of Parkinson ’s disease (PD) and is believed to further exacerbate the progressive degeneration of dopaminergic neurons. Current therapies are unable to prevent the disease progression. A significant association has been demonstrated between PD and low levels of vitamin D in patients serum, and vitamin D suppl ement appears to have a beneficial clinical effect. Herein, we investigated whether vitamin D administered orally in a 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine (MPTP)-induced preclinical animal model of PD protects against ...
Source: Journal of NeuroImmune Pharmacology - December 16, 2016 Category: Drugs & Pharmacology Source Type: research

Cathepsin B Improves ß-Amyloidosis and Learning and Memory in Models of Alzheimer’s Disease
AbstractAmyloid- ß (Aß) precursor protein (APP) metabolism engages neuronal endolysosomal pathways for Aß processing and secretion. In Alzheimer’s disease (AD), dysregulation of APP leads to excess Aß and neuronal dysfunction; suggesting that neuronal APP/Aß trafficking can be targeted for therapeutic gain. C athepsin B (CatB) is a lysosomal cysteine protease that can lower Aß levels. However, whether CatB-modulation of Aß improves learning and memory function deficits in AD is not known. To this end, progenitor neurons were infected with recombinant adenovirus expressing Cat...
Source: Journal of NeuroImmune Pharmacology - December 13, 2016 Category: Drugs & Pharmacology Source Type: research

B Lymphocytes Express Pomc mRNA, Processing Enzymes and β-Endorphin in Painful Inflammation
This study aims to decipher the processing of POMC in lymphocyte subsets in a rat model of unilateral painful hindpaw inflammation. Lymphocytes, isolated from popliteal lymph nodes, were separated into B-cells, T-cells, T-helper cells and cytotoxic T-cells using magnetic cell sorting, and were examined by polymerase chain reaction, immunofluorescence and radioimmunoassay. At 2  h of inflammation, POMC exon 2–3 mRNA was mostly expressed in B- but not in T-cells. Prohormone convertase 1 (PC1) mRNA and protein were upregulated in B-cells and T-helper cells. Prohormone convertase 2 (PC2) was expressed in T- and B-ce...
Source: Journal of NeuroImmune Pharmacology - November 11, 2016 Category: Drugs & Pharmacology Source Type: research

Nanoformulated Antiretrovirals for Penetration of the Central Nervous System: State of the Art
AbstractThe central nervous system is a very challenging HIV-1 sanctuary. But, despite complete suppression of plasmatic viral replication with current antiretroviral therapy, signs of HIV-1 replication can still be found in the cerebrospinal fluid in some patients. The main limitation to achieving HIV-1 eradication from the brain is related to the suboptimal concentrations of antiretrovirals within this site, due to their low permeation across the blood –brain barrier. In recent years, a number of reliable nanotechnological strategies have been developed with the aim of enhancing antiretroviral drug penetration acro...
Source: Journal of NeuroImmune Pharmacology - November 10, 2016 Category: Drugs & Pharmacology Source Type: research

Phenotype of Antigen Unexperienced T H Cells in the Inflamed Central Nervous System in Experimental Autoimmune Encephalomyelitis
AbstractMultiple sclerosis is a chronic, disseminated inflammation of the central nervous system which is thought to be driven by autoimmune T cells. Genetic association studies in multiple sclerosis and a large number of studies in the animal model of the disease support a role for effector/memory T helper cells. However, the mechanisms underlying relapses, remission and chronic progression in multiple sclerosis or the animal model experimental autoimmune encephalomyelitis, are not clear. In particular, there is only scarce information on the role of central nervous system-invading naive T helper cells in these processes....
Source: Journal of NeuroImmune Pharmacology - November 10, 2016 Category: Drugs & Pharmacology Source Type: research

Blood Brain Barrier Impairment in HIV-Positive Na ïve and Effectively Treated Patients: Immune Activation Versus Astrocytosis
AbstractBlood brain barrier (BBB) damage is a common feature in central nervous system infections by HIV and it may persist despite effective antiretroviral therapy. Astrocyte involvement has not been studied in this setting. Patients were enrolled in an ongoing prospective study and subjects with central nervous system-affecting disorders were excluded. Patients were divided into two groups: treated subjects with cerebrospinal fluid (CSF) HIV RNA
Source: Journal of NeuroImmune Pharmacology - November 8, 2016 Category: Drugs & Pharmacology Source Type: research

Dynamic Modulation of Microglia/Macrophage Polarization by miR-124 after Focal Cerebral Ischemia
This study indicates that miR-124 administration before the peak of the pro-inflammatory process of stroke is most effectiv e in support of increasing the rehabilitation opportunity in the sub-acute phases of stroke. Our findings highlight the important role of immune cells after stroke and the therapeutic relevance of their polarization balance. (Source: Journal of NeuroImmune Pharmacology)
Source: Journal of NeuroImmune Pharmacology - November 6, 2016 Category: Drugs & Pharmacology Source Type: research

Angiotensin Converting Enzyme Inhibitors Ameliorate Brain Inflammation Associated with Microglial Activation: Possible Implications for Alzheimer ’s Disease
AbstractAngiotensin converting enzyme (ACE) converts Angiotensin I to a potent vasoconstrictor angiotensin II (ANG II). ACE inhibitors (ACEIs) are widely used for the management of hypertension. All components of the renin-angiotensin system (RAS) have also been identified in the brain. In addition to cytokines, neuromodulators such as ANG II can induce neuroinflammation. Moreover, in Alzheimer ’s disease (AD) models, where neuroinflammation occurs and is thought to contribute to the propagation of the disease, increased levels of ANG II and ACE have been detected. However, the specific effect of ACEIs on neuroinflam...
Source: Journal of NeuroImmune Pharmacology - November 6, 2016 Category: Drugs & Pharmacology Source Type: research

A Novel A β B-Cell Epitope Vaccine (rCV01) for Alzheimer’s Disease Improved Synaptic and Cognitive Functions in 3 × Tg-AD Mice
AbstractAlzheimer ’s disease (AD) is a neurodegenerative disorder characterized by a progressive amyloid-β accumulation, loss of cognitive abilities, and synaptic alterations. Given the remarkable recovery of cognition in AD models of targeting-Aβ immunotherapy, we sought to determine the molecular correlate(s) a ssociated with improvement. We evaluated the efficacy of a recombinant chimeric 6Aβ15-T antigen formulated with alum adjuvant as a novel Aβ B-cell epitope vaccine (rCV01) in 3 × Tg-AD mice. rCV01 elicited robust Th2-polarized Aβ-specific antibodies without autoimmune ...
Source: Journal of NeuroImmune Pharmacology - November 6, 2016 Category: Drugs & Pharmacology Source Type: research

Efficacy of N -Acetylserotonin and Melatonin in the EAE Model of Multiple Sclerosis
AbstractMelatonin andN-acetylserotonin (NAS) are tryptophan metabolites that have potent anti-oxidant, anti-inflammatory and neuroprotective properties in several animal models of neurological injury and disease including multiple sclerosis (MS). The therapeutic effect of NAS has not been reported previously in experimental autoimmune encephalomyelitis (EAE), a commonly used animal model of MS. Using a MOG-peptide induced EAE mouse model we examined the effects of melatonin and NAS on clinical score, inflammatory markers, free radical generation, and sparing of axons, oligodendrocytes and myelin. We found that NAS and mela...
Source: Journal of NeuroImmune Pharmacology - November 6, 2016 Category: Drugs & Pharmacology Source Type: research

Extracellular Mitochondria and Mitochondrial Components Act as Damage-Associated Molecular Pattern Molecules in the Mouse Brain
AbstractMitochondria and mitochondrial debris are found in the brain ’s extracellular space, and extracellular mitochondrial components can act as damage associated molecular pattern (DAMP) molecules. To characterize the effects of potential mitochondrial DAMP molecules on neuroinflammation, we injected either isolated mitochondria or mitochondrial DNA (mtDNA) into hippocampi of C57BL/6 mice and seven days later measured markers of inflammation. Brains injected with whole mitochondria showed increasedTnf α and decreasedTrem2 mRNA, increased GFAP protein, and increased NF κB phosphorylation. Some of these ...
Source: Journal of NeuroImmune Pharmacology - November 6, 2016 Category: Drugs & Pharmacology Source Type: research

Erratum to: Atorvastatin Modulates Regulatory T Cells and Attenuates Cerebral Damage in a Model of Transient Middle Cerebral Artery Occlusion in Rats
(Source: Journal of NeuroImmune Pharmacology)
Source: Journal of NeuroImmune Pharmacology - October 14, 2016 Category: Drugs & Pharmacology Source Type: research

Anti-Inflammatory and Neuroprotective Effects of PGE 2 EP4 Signaling in Models of Parkinson ’s Disease
AbstractInflammation is a ubiquitous factor accompanying normal aging and neurodegeneration, and recent studies indicate a major contribution of inducible cyclooxygenase (COX-2) and its downstream prostaglandin signaling pathways in modulating neuroinflammatory responses and neuronal function. We have previously shown that the prostaglandin PGE2 receptor EP4 suppresses innate immune responses in models of systemic inflammation. Here we investigated the role of the EP4 receptor in models of Parkinson ’s disease (PD). Systemic co-administration of the EP4 agonist ONO-AE1–329 with the neurotoxin 1-methyl-4-phenyl-...
Source: Journal of NeuroImmune Pharmacology - October 12, 2016 Category: Drugs & Pharmacology Source Type: research

Targeting Oxidative Stress, Cytokines and Serotonin Interactions Via Indoleamine 2, 3 Dioxygenase by Coenzyme Q10: Role in Suppressing Depressive Like Behavior in Rats
This study was designed to investigate the hypothesis that CoQ10 by its anti-oxidant and anti-inflammatory potentials can alleviate depressive- like behavior by restoring the balance of the tryptophan catabolites kynurenine/serotonin toward the serotonin pathway by down-regulation of hippocampal indoleamine 2,3-dioxygenase 1 (IDO-1). Depressive-like behavior was induced by chronic unpredictable mild stress (CUMS) protocol including food or water deprivation, cage tilting, reversed light cycle etc. Male Wistar rats were randomly divided into five groups; Control, CUMS, CUMS and CoQ10 (50,100 and 200  mg/kg/day i.p. res...
Source: Journal of NeuroImmune Pharmacology - October 11, 2016 Category: Drugs & Pharmacology Source Type: research

HIV-1 Viral Protein R Activates NLRP3 Inflammasome in Microglia: implications for HIV-1 Associated Neuroinflammation
This study provides a new therapeutic perspective for HIV-associated neuropsychiatric disease. (Source: Journal of NeuroImmune Pharmacology)
Source: Journal of NeuroImmune Pharmacology - October 10, 2016 Category: Drugs & Pharmacology Source Type: research

A Gap in Time: Extending our Knowledge of Temporal Processing Deficits in the HIV-1 Transgenic Rat
AbstractApproximately 50  % of HIV-1 seropositive individuals develop HIV-1 associated neurocognitive disorders (HAND), which commonly include alterations in executive functions, such as inhibition, set shifting, and complex problem solving. Executive function deficits in HIV-1 are fairly well characterized, however, relat ively few studies have explored the elemental dimensions of neurocognitive impairment in HIV-1. Deficits in temporal processing, caused by HIV-1, may underlie the symptoms of impairment in higher level cognitive processes. Translational measures of temporal processing, including cross-modal prepulse...
Source: Journal of NeuroImmune Pharmacology - October 3, 2016 Category: Drugs & Pharmacology Source Type: research

Modulation of Binge-like Ethanol Consumption by IL-10 Signaling in the Basolateral Amygdala
AbstractExcessive ethanol consumption alters the neuroimmune system and particularly impacts the cytokine milieu of the CNS. Cytokine dysregulation has been shown to underlie addictive-like behaviors including alcohol abuse; however, many studies focus primarily on the proinflammatory cytokine profile during  alcohol dependence. The current study furthers this research by determining the impact of excessive ethanol consumption on interleukin-10 (IL-10) and interleukin-4 (IL-4) activity in a model of non-dependent binge consumption called the “drinking in the dark” (DID) paradigm. Furthermore, the a bility ...
Source: Journal of NeuroImmune Pharmacology - September 17, 2016 Category: Drugs & Pharmacology Source Type: research

Complexes of Peptide Blockers with Kv1.6 Pore Domain: Molecular Modeling and Studies with KcsA-Kv1.6 Channel
AbstractPotassium voltage-gated Kv1.6 channel, which is distributed primarily in neurons of central and peripheral nervous systems, is of significant physiological importance. To date, several high-affinity Kv1.6-channel blockers are known, but the lack of selective ones among them hampers the studies of tissue localization and functioning of Kv1.6 channels. Here we present an approach to advanced understanding of interactions of peptide toxin blockers with a Kv1.6 pore. It combines molecular modeling studies and an application of a new bioengineering system based on a KcsA-Kv1.6 hybrid channel for the quantitative fluores...
Source: Journal of NeuroImmune Pharmacology - September 17, 2016 Category: Drugs & Pharmacology Source Type: research

Caffeine Blocks HIV-1 Tat-Induced Amyloid Beta Production and Tau Phosphorylation
AbstractThe increased life expectancy of people living with HIV-1 who are taking effective anti-retroviral therapeutics is now accompanied by increased Alzheimer ’s disease (AD)-like neurocognitive problems and neuropathological features such as increased levels of amyloid beta (Aβ) and phosphorylated tau proteins. Others and we have shown that HIV-1 Tat promotes the development of AD-like pathology. Indeed, HIV-1 Tat once endocytosed into neurons can alt er morphological features and functions of endolysosomes as well as increase Aβ generation. Caffeine has been shown to have protective actions against AD ...
Source: Journal of NeuroImmune Pharmacology - September 15, 2016 Category: Drugs & Pharmacology Source Type: research

Atorvastatin Modulates Regulatory T Cells and Attenuates Cerebral Damage in a Model of Transient Middle Cerebral Artery Occlusion in Rats
AbstractRegulatory T cells (Tregs) inhibit the activation of the immune response which could down-regulate the systemic and focal activation observed during ischemic stroke. In fact, in animal models, Tregs infiltrate the infarcted brain and reduce the pro-inflammatory cytokine production and infarct volume, mainly in late stages of ischemia. Recently, an expansion and greater suppressive capacity of circulating Tregs after treatment with statins was observed, in addition to their cardio- and neuroprotective actions demonstrated previously. Thus, to determine whether Treg modulation mediated by statins can also be benefici...
Source: Journal of NeuroImmune Pharmacology - September 10, 2016 Category: Drugs & Pharmacology Source Type: research

Bacterial Meningitis in Patients using Immunosuppressive Medication: a Population-based Prospective Nationwide Study
AbstractWe studied occurrence, presentation, disease course, effect of adjunctive dexamethasone, and prognosis of bacterial meningitis in patients using immunosuppressive medication. Patients were selected from our nationwide, prospective cohort on community-acquired bacterial meningitis performed from March 1, 2006 through October 31, 2014. Eighty-seven of 1447 episodes (6  %) of bacterial meningitis occurred in patients using immunosuppressive medication, and consisted of corticosteroids in 82 %. Patients with bacterial meningitis using immunosuppressive medication were less likely to present with headache (P&n...
Source: Journal of NeuroImmune Pharmacology - September 9, 2016 Category: Drugs & Pharmacology Source Type: research

Precision Medicine for Tobacco Dependence: Development and Validation of the Nicotine Metabolite Ratio
AbstractQuitting smoking significantly reduces the risk of tobacco-related morbidity and mortality, yet there is a high rate of relapse amongst smokers who try to quit. Phenotypic biomarkers have the potential to improve smoking cessation outcomes by identifying the best available treatment for an individual smoker. In this review, we introduce the nicotine metabolite ratio (NMR) as a reliable and stable phenotypic measure of nicotine metabolism that can guide smoking cessation treatment among smokers who wish to quit. We address how the NMR accounts for sources of variation in nicotine metabolism including genotype and ot...
Source: Journal of NeuroImmune Pharmacology - August 13, 2016 Category: Drugs & Pharmacology Source Type: research

Immune Modulation and Prevention of Autoimmune Disease by Repeated Sequences from Parasites Linked to Self Antigens
This study describes the use of repetitive structures from parasites linked to defined T cell epitopes as an effective method to induce antigen-specific tolerance with potential applicability for the treatment and prevention of autoimmune diseases. (Source: Journal of NeuroImmune Pharmacology)
Source: Journal of NeuroImmune Pharmacology - August 12, 2016 Category: Drugs & Pharmacology Source Type: research

Effects of HIV and Methamphetamine on Brain and Behavior: Evidence from Human Studies and Animal Models
AbstractMethamphetamine (Meth) use is frequent among HIV-infected persons. Combined HIV and Meth insults may exacerbate neural injury in vulnerable neuroanatomic structures or circuitries in the brain, leading to increased behavioral disturbance and cognitive impairment. While acute and chronic effects of Meth in humans and animal models have been studied for decades, the neurobehavioral effects of Meth in the context of HIV infection are much less explored. In-depth understanding of the scope of neurobehavioral phenotypes and mechanisms in HIV/Meth intersection is needed. The present report summarizes published research f...
Source: Journal of NeuroImmune Pharmacology - August 2, 2016 Category: Drugs & Pharmacology Source Type: research

Promoting Global Health — Prevention and Treatment of Substance Abuse and HIV in Asia
AbstractThis special issue contains 20 papers including 3 Perspectives, 1 Brief Report, 6 Invited Reviews, and 10 Original Articles, which highlight the work by presenters at the second meeting of the biennial Conference Series to Promote Global Health held on April 22 –24, 2015 in Hangzhou, Zhejiang, China. These papers focused on the prevalent substance misuse of amphetamine-type-stimulants and opioids, and the increasing prevalence of HIV-infection in Asian countries. The Conference Series is sponsored by the National Institute on Drug Abuse of the U.S. Natio nal Institutes of Health, with the goal of exchanging k...
Source: Journal of NeuroImmune Pharmacology - August 2, 2016 Category: Drugs & Pharmacology Source Type: research

Advances in Targeted Drug Delivery Approaches for the Central Nervous System Tumors: The Inspiration of Nanobiotechnology
Abstract At present, brain tumor is among the most challenging diseases to treat and the therapy is limited by the lack of effective methods to deliver anticancer agents across the blood-brain barrier (BBB). BBB is a selective barrier that separates the circulating blood from the brain extracellular fluid. In its neuroprotective function, BBB prevents the entry of toxins, as well as most of anticancer agents and is the main impediment for brain targeted drug delivery approaches. Nanotechnology-based delivery systems provide an attractive strategy to cross the BBB and reach the central nervous system (CNS). The incorporati...
Source: Journal of NeuroImmune Pharmacology - July 23, 2016 Category: Drugs & Pharmacology Source Type: research

Increase of Alternatively Activated Antigen Presenting Cells in Active Experimental Autoimmune Encephalomyelitis
Abstract The importance of CD11c+ antigen-presenting cells (APCs) in the pathogenesis of experimental autoimmune encephalomyelitis (EAE) is well accepted and the gate keeper function of perivascular CD11c+ APCs has been demonstrated. CD11c can be expressed by APCs from external sources or by central nervous system (CNS) resident APCs such as microglia. Yet, changes in the gene expression pattern of CNS CD11c+ APCs during disease are still unclear and differentially expressed genes might play a decisive role in EAE progression. Due to their low numbers in the diseased brain and due to the absence of considerable nu...
Source: Journal of NeuroImmune Pharmacology - July 16, 2016 Category: Drugs & Pharmacology Source Type: research

Effect of Fingolimod-Treatment on Blood Lipid Profiles of Multiple Sclerosis Patients
(Source: Journal of NeuroImmune Pharmacology)
Source: Journal of NeuroImmune Pharmacology - July 7, 2016 Category: Drugs & Pharmacology Source Type: research

Biodegradable Nanoparticles for Delivery of Therapeutics in CNS Infection
Abstract Despite the significant advances in neurological medicine, it remains difficult to treat ailments directly involving the brain. The blood brain barrier (BBB) is a tightly regulated, selectively permeable barrier that restricts access from the blood into the brain extracellular fluid (BEF). Many conditions such as tumors or infections in the brain are difficult to treat due to the fact that drugs and other therapeutic agents are unable to easily pass through this relatively impermeable barrier. Human Immunodeficiency Virus (HIV) presents a particular problem as it is able to remain dormant in the brain for...
Source: Journal of NeuroImmune Pharmacology - July 2, 2016 Category: Drugs & Pharmacology Source Type: research

Neuropharmacologic Approaches to Restore the Brain ’s Microenvironment
Abstract Maintaining the central nervous system microenvironment after injury, infection, inflammatory and degenerative diseases is contingent upon adequate control of glial homeostatic functions. Disease is caused by microbial, environmental and endogenous factors that compromise ongoing nervous system functions. The final result is neuronal injury, dropout and nerve connection loss, and these underlie the pathobiology of Alzheimer ’s and Parkinson’s disease, amyotrophic lateral sclerosis, stroke, and bacterial, parasitic and viral infections. However, what promotes disease are homeostatic changes in the brai...
Source: Journal of NeuroImmune Pharmacology - June 28, 2016 Category: Drugs & Pharmacology Source Type: research

Neuropharmacologic Approaches to Restore the Brain’s Microenvironment
Abstract Maintaining the central nervous system microenvironment after injury, infection, inflammatory and degenerative diseases is contingent upon adequate control of glial homeostatic functions. Disease is caused by microbial, environmental and endogenous factors that compromise ongoing nervous system functions. The final result is neuronal injury, dropout and nerve connection loss, and these underlie the pathobiology of Alzheimer’s and Parkinson’s disease, amyotrophic lateral sclerosis, stroke, and bacterial, parasitic and viral infections. However, what promotes disease are homeostatic changes in t...
Source: Journal of NeuroImmune Pharmacology - June 28, 2016 Category: Drugs & Pharmacology Source Type: research

The Neural Cell Adhesion Molecule-Derived (NCAM)-Peptide FG Loop (FGL) Mobilizes Endogenous Neural Stem Cells and Promotes Endogenous Regenerative Capacity after Stroke
Abstract The neural cell adhesion molecule (NCAM)-derived peptide FG loop (FGL) modulates synaptogenesis, neurogenesis, and stem cell proliferation, enhances cognitive capacities, and conveys neuroprotection after stroke. Here we investigated the effect of subcutaneously injected FGL on cellular compartments affected by degeneration and regeneration after stroke due to middle cerebral artery occlusion (MCAO), namely endogenous neural stem cells (NSC), oligodendrocytes, and microglia. In addition to immunohistochemistry, we used non-invasive positron emission tomography (PET) imaging with the tracer [18F]-fluoro-L-...
Source: Journal of NeuroImmune Pharmacology - June 28, 2016 Category: Drugs & Pharmacology Source Type: research

Cinnamon Converts Poor Learning Mice to Good Learners: Implications for Memory Improvement
This study underlines the importance of cinnamon, a commonly used natural spice and flavoring material, and its metabolite sodium benzoate (NaB) in converting poor learning mice to good learning ones. NaB, but not sodium formate, was found to upregulate plasticity-related molecules, stimulate NMDA- and AMPA-sensitive calcium influx and increase of spine density in cultured hippocampal neurons. NaB induced the activation of CREB in hippocampal neurons via protein kinase A (PKA), which was responsible for the upregulation of plasticity-related molecules. Finally, spatial memory consolidation-induced activation of CREB and ex...
Source: Journal of NeuroImmune Pharmacology - June 24, 2016 Category: Drugs & Pharmacology Source Type: research

Effects of Moderate Prenatal Alcohol Exposure during Early Gestation in Rats on Inflammation across the Maternal-Fetal-Immune Interface and Later-Life Immune Function in the Offspring
Abstract During early brain development, microglial activation can negatively impact long-term neuroimmune and cognitive outcomes. It is well-known that significant alcohol exposure during early gestation results in a number of cognitive deficits associated with fetal alcohol spectrum disorders (FASD). Additionally, microglia are activated following high levels of alcohol exposure in rodent models of FASD. We sought to examine whether moderate prenatal alcohol exposure (70 mg/dL blood alcohol concentration) activates microglia in the fetal rat brain, and whether moderate fetal alcohol exposure has long-term n...
Source: Journal of NeuroImmune Pharmacology - June 18, 2016 Category: Drugs & Pharmacology Source Type: research

Cell Mediated Photothermal Therapy of Brain Tumors
Abstract Gold based nanoparticles with strong near infra-red (NIR) absorption are ideally suited for photothermal therapy (PTT) of brain tumors. The goal of PTT is to induce rapid heating in tumor tissues while minimizing thermal diffusion to normal brain. PTT efficacy is sensitively dependent on both nanoparticle concentration and distribution in tumor tissues. Nanoparticle delivery via passive approaches such as the enhanced permeability and retention (EPR) effect is unlikely to achieve sufficient nanoparticle concentrations throughout tumor volumes required for effective PTT. A simple approach for improving tum...
Source: Journal of NeuroImmune Pharmacology - June 11, 2016 Category: Drugs & Pharmacology Source Type: research

Electro-Magnetic Nano-Particle Bound Beclin1 siRNA Crosses the Blood –Brain Barrier to Attenuate the Inflammatory Effects of HIV-1 Infection in Vitro
Abstract The purpose of this study was to evaluate a novel drug delivery system comprised of ferric-cobalt electro-magnetic nano-material (CoFe2O4@ BaTiO3; MENP) bound to siRNA targeting Beclin1 (MENP-siBeclin1) to cross the blood –brain barrier (BBB) and attenuate the neurotoxic effects of HIV-1 infection in the central nervous system following on-demand release of siRNA using an in vitro primary human BBB model. Beclin1 is a key protein in the regulation of the autophagy pathway and we have recently demonstrated the impor tance of Beclin1 in regulating viral replication and viral-induced inflammation in HIV-1-infe...
Source: Journal of NeuroImmune Pharmacology - June 10, 2016 Category: Drugs & Pharmacology Source Type: research

Reduced Noradrenergic Signaling in the Spleen Capsule in the Absence of CB 1 and CB 2 Cannabinoid Receptors
Abstract The spleen is a visceral organ that contracts during hypoxia to expel erythrocytes and immune cells into the circulation. Spleen contraction is under the control of noradrenergic sympathetic innervation. The activity of noradrenergic neurons terminating in the spleen capsule is regulated by α2-adrenergic receptors (AR). Interactions between endogenous cannabinoid signaling and noradrenergic signaling in other organ systems suggest endocannabinoids might also regulate spleen contraction. Spleens from mice congenitally lacking both CB1 and CB2 cannabinoid receptors (Cnr1 -/- ...
Source: Journal of NeuroImmune Pharmacology - June 10, 2016 Category: Drugs & Pharmacology Source Type: research

Electro-Magnetic Nano-Particle Bound Beclin1 siRNA Crosses the Blood–Brain Barrier to Attenuate the Inflammatory Effects of HIV-1 Infection in Vitro
Abstract The purpose of this study was to evaluate a novel drug delivery system comprised of ferric-cobalt electro-magnetic nano-material (CoFe2O4@ BaTiO3; MENP) bound to siRNA targeting Beclin1 (MENP-siBeclin1) to cross the blood–brain barrier (BBB) and attenuate the neurotoxic effects of HIV-1 infection in the central nervous system following on-demand release of siRNA using an in vitro primary human BBB model. Beclin1 is a key protein in the regulation of the autophagy pathway and we have recently demonstrated the importance of Beclin1 in regulating viral replication and viral-induced inflammation in HIV-...
Source: Journal of NeuroImmune Pharmacology - June 10, 2016 Category: Drugs & Pharmacology Source Type: research

Perspectives on Dual Targeting Delivery Systems for Brain Tumors
Abstract Brain tumor remains one of the most serious threats to human beings. Different from peripheral tumors, drug delivery to brain tumor is largely restricted by the blood brain barrier (BBB). To fully conquer this barrier and specifically deliver drugs to brain tumor, dual targeting delivery systems were explored, which are functionalized with two active targeting ligands: one to the BBB and the other to the brain tumor. The development of dual targeting delivery system is still in its early stage, and attentions need to be paid to issues and concerns that remain unresolved in future studies. (Source: Journal...
Source: Journal of NeuroImmune Pharmacology - June 8, 2016 Category: Drugs & Pharmacology Source Type: research

Confronting the HIV, Tuberculosis, Addiction, and Incarceration Syndemic in Southeast Asia: Lessons Learned from Malaysia
Abstract Throughout Southeast Asia, repressive drug laws have resulted in high rates of imprisonment in people who inject drugs (PWID) and people living with HIV (PLH), greatly magnifying the harm associated with HIV, tuberculosis, and addiction. We review findings from Malaysia’s largest prison to describe the negative synergistic effects of HIV, tuberculosis, addiction, and incarceration that contribute to a ‘perfect storm’ of events challenging public and personal health and offer insights into innovative strategies to control these converging epidemics. The majority of PLH who are impris...
Source: Journal of NeuroImmune Pharmacology - May 24, 2016 Category: Drugs & Pharmacology Source Type: research

Tailoring Lipid and Polymeric Nanoparticles as siRNA Carriers towards the Blood-Brain Barrier – from Targeting to Safe Administration
Abstract Blood-brain barrier is a tightly packed layer of endothelial cells surrounding the brain that acts as the main obstacle for drugs enter the central nervous system (CNS), due to its unique features, as tight junctions and drug efflux systems. Therefore, since the incidence of CNS disorders is increasing worldwide, medical therapeutics need to be improved. Consequently, aiming to surpass blood-brain barrier and overcome CNS disabilities, silencing P-glycoprotein as a drug efflux transporter at brain endothelial cells through siRNA is considered a promising approach. For siRNA enzymatic protection and effici...
Source: Journal of NeuroImmune Pharmacology - May 21, 2016 Category: Drugs & Pharmacology Source Type: research

Platelet Activating Factor (PAF) Receptor Deletion or Antagonism Attenuates Severe HSV-1 Meningoencephalitis
Abstract Herpes simplex virus type 1 (HSV-1) is a human pathogen that may cause severe encephalitis. The exacerbated immune response against the virus contributes to the disease severity and death. Platelet activating factor (PAF) is a mediator capable of inducing increase in vascular permeability, production of cytokines on endothelial cells and leukocytes. We aimed to investigate the activation of PAF receptor (PAFR) and its contribution to the severity of the inflammatory response in the brain following HSV-1 infection. C57BL/6 wild-type (WT) and PAFR deficient (PAFR−/−) mice were inoculated intracr...
Source: Journal of NeuroImmune Pharmacology - May 19, 2016 Category: Drugs & Pharmacology Source Type: research

Neuroimaging the Effectiveness of Substance Use Disorder Treatments
Abstract Neuroimaging techniques to measure the function and biochemistry of the human brain such as positron emission tomography (PET), proton magnetic resonance spectroscopy (1H MRS), and functional magnetic resonance imaging (fMRI), are powerful tools for assessing neurobiological mechanisms underlying the response to treatments in substance use disorders. Here, we review the neuroimaging literature on pharmacological and behavioral treatment in substance use disorder. We focus on neural effects of medications that reduce craving (e.g., naltrexone, bupropion hydrochloride, baclofen, methadone, varenicline) and ...
Source: Journal of NeuroImmune Pharmacology - May 16, 2016 Category: Drugs & Pharmacology Source Type: research

Glycosyl Phosphatidylinositol-Anchored C34 Peptide Derived From Human Immunodeficiency Virus Type 1 Gp41 Is a Potent Entry Inhibitor
Abstract Lipid rafts of the plasma membrane have been shown to be gateways for HIV-1 budding and entry. In nature, many glycosyl-phosphatidylinositol (GPI) anchored proteins are targeted to the lipid rafts. In the present study we constructed two fusion genes, in which C34 peptide or AVF peptide control was genetically linked with a GPI-attachment signal. Recombinant lentiviruses expressing the fusion genes were used to transduce TZM.bl and CEMss-CCR5 cells. Here, we show that with a GPI attachment signal both C34 and AVF are targeted to the lipid rafts through a GPI anchor. GPI-C34, but not GPI-AVF, in transduced...
Source: Journal of NeuroImmune Pharmacology - May 7, 2016 Category: Drugs & Pharmacology Source Type: research

SIV Infection Impairs the Central Nervous System in Chinese Rhesus Macaques
Abstract The central nervous system (CNS) impairment is a consequence seen in SIV infection of rhesus macaques of Indian-origin, which is more common in infected macaques with rapid disease progression than in those with conventional disease progression. Here, we investigated the CNS damages in SIVmac239-infected Chinese rhesus macaques. We demonstrated that SIV infection of Chinese macaques could cause neuropathological impairments, which was evidenced by appearance of SIV-RNA positive cells, the infiltration of activated macrophages and abundant multinucleated giant cells (MNGCs) in the different regions of the ...
Source: Journal of NeuroImmune Pharmacology - May 6, 2016 Category: Drugs & Pharmacology Source Type: research

CXCR4 and NMDA Receptors Are Functionally Coupled in Rat Hippocampal Noradrenergic and Glutamatergic Nerve Endings
This study aims to assess whether the chemokine CXC4 receptors (CXCR4s) has a role in the gp120-mediated effects. The effect of CXCL12, the endogenous ligand at CXCR4, on the NMDA-mediated releasing activity was therefore investigated. Rat hippocampal synaptosomes were preloaded with [3H]noradrenaline ([3H]NA) or [3H]D-aspartate ([3H]D-Asp) and acutely exposed to CXCL12, to NMDA or to both agonists. CXCL12, inactive on its own, facilitated the NMDA-evoked tritium release. The NMDA antagonist MK-801 abolished the NMDA/CXCL12-evoked tritium release of both radiolabelled tracers, while the CXCR4 antagonist AMD 3100 halved it,...
Source: Journal of NeuroImmune Pharmacology - May 5, 2016 Category: Drugs & Pharmacology Source Type: research