BrainImmune: Trends in Neuroendocrine Immunology http://www.brainimmune.com Expert views & state of art in neuroendocrine immunology & stress-immunity research by BrainImmune.com. Both fundamental & clinical aspects and their impacts on health & disease. Mon, 20 Aug 2018 11:24:10 +0000 en-US hourly 1 https://wordpress.org/?v=4.9.8 107933628 Fibromyalgia Syndrome and Widespread Pain: From Construction to Relevant Recognition http://www.brainimmune.com/fibromyalgia-syndrome-widespread-pain/ Sat, 18 Aug 2018 13:11:56 +0000 http://www.brainimmune.com/?p=6867 The 2018, 1st edition book Fibromyalgia Syndrome and Widespread Pain: From Construction to Relevant Recognition is authored by Winfried Haüser and Serge Perrot and published by IASP. Fibromyalgia is a condition that mostly affects women and is characterized by chronic widespread pain, paresthesias, allodynia, fatigue, sleep difficulties and cognitive impairment. “In fact, the name ‘fibromyalgia’ […]

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Fibromyalgia Syndrome Widespread PainThe 2018, 1st edition book Fibromyalgia Syndrome and Widespread Pain: From Construction to Relevant Recognition is authored by Winfried Haüser and Serge Perrot and published by IASP.

Fibromyalgia is a condition that mostly affects women and is characterized by chronic widespread pain, paresthesias, allodynia, fatigue, sleep difficulties and cognitive impairment.

“In fact, the name ‘fibromyalgia’ is recent, proposed by Hench in 1976, but the story began long before this labeling. Over time, its story has been influenced by current concepts, from muscle disorder to psychology, from genetic predisposition to hormonal dysfunction, and finally with important findings related to the neurosciences, from small fibers to brain”.

Recent research suggests that fibromyalgia is a neuropathic syndrome affecting small sensory and sympathetic nerve fibers. An increasing body of evidence also indicates that cytokines and chemokines contribute to the pathogenesis of fibromyalgia.

The Fibromyalgia Syndrome and Widespread Pain is published under the auspices of the International Association for the Study of Pain. The book offers a holistic guide to the understanding and management of fibromyalgia syndrome, bringing together contributors and approaches from the worlds of medicine, complementary medicine, physical therapy, pharmacology and psychology. A unique and necessary approach to this debilitating condition!

Chapters tackle a range of topics, including the history and clinical features and criteria of fibromyalgia, the variety of treatment and management options, differential diagnosis, epidemiology, genetic factors, and more.

Succinct, precise writing style brings a focus to the material, highlighting what’s really important. Considers social, economic, psychological, and medical/clinical constructions of fibromyalgia. Includes a true-to-life account from a patient of what it’s like to live with fibromyalgia.

Paperback: 312 pages; Publisher: IASP; 1 edition (August 4, 2018)


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Cytokines: From Basic Mechanisms of Cellular Control to New Therapeutics http://www.brainimmune.com/cytokines-basic-mechanisms-cellular-control/ Thu, 16 Aug 2018 11:44:42 +0000 http://www.brainimmune.com/?p=6850 Cytokines: From Basic Mechanisms of Cellular Control to New Therapeutics is a new book edited by Robert Schreiber and Warren Leonard and published by Cold Spring Harbor Laboratory Press. According to Joost Oppenheim the definition of cytokines can be broadly based on their function as intercellular signals. Thus, cytokines (e.g., interleukins and interferons) are small […]

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Cytokines Basic Mechanisms Cellular ControlCytokines: From Basic Mechanisms of Cellular Control to New Therapeutics is a new book edited by Robert Schreiber and Warren Leonard and published by Cold Spring Harbor Laboratory Press.

According to Joost Oppenheim the definition of cytokines can be broadly based on their function as intercellular signals. Thus, cytokines (e.g., interleukins and interferons) are small signaling proteins that are essential for communication between cells.

This is particularly relevant to the immune system. These ‘hormones of the immune system’ are important regulators of the immunity, helping to control lymphocyte development and function, orchestrate inflammation, and defeat microbial and viral invaders. But they also play important roles in the nervous system, embryonic development, and diseases such as cancer.

Written and edited by experts in the field, this collection from Cold Spring Harbor Perspectives in Biology covers the spectrum of cytokines that are produced and their roles in normal physiology and disease. The contributors examine the numerous cytokines and their cognate receptors, the downstream signaling mechanisms (e.g., JAK-STAT pathways) that mediate the effects of cytokines on cells, and the regulators that keep them in check (e.g., long noncoding RNAs and the SOCS and IRF protein families). These molecular interactions are discussed in the context of their physiological effects; the roles of cytokines in the development and activities of the immune system are emphasized.

The authors also explore how the actions of cytokines may be modulated for treating patients with autoimmune disorders, immunodeficiency, infections, allergies, and cancer. Thus, this volume is an indispensable reference not only for cell biologists and immunologists but for all who are interested in targeting cytokine signaling for therapeutic purposes.

Series: Perspectives CSHL; Hardcover: 350 pages; Publisher: Cold Spring Harbor Laboratory Press; 1 edition (May 31, 2018)

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Cytokines: From Basic Mechanisms of Cellular Control to New Therapeutics (Perspectives CSHL)

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The Cytokines of the Immune System: The Role of Cytokines in Disease Related to Immune Response http://www.brainimmune.com/cytokines-of-the-immune-system/ Sat, 11 Aug 2018 14:51:51 +0000 http://www.brainimmune.com/?p=6830 The cytokines of the immune system: The role of cytokines in disease related to immune response describes the role and functions of cytokines and links them to physiology and pathology. The Cytokines of the Immune System is authored by Zlatko Dembic and published by Academic Press. Homeostasis within the immune system is largely dependent on […]

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Cytokines of the Immune SystemThe cytokines of the immune system: The role of cytokines in disease related to immune response describes the role and functions of cytokines and links them to physiology and pathology. The Cytokines of the Immune System is authored by Zlatko Dembic and published by Academic Press.

Homeostasis within the immune system is largely dependent on cytokines, the chemical messengers between immune cells, which play crucial roles in mediating inflammatory and immune responses. These diverse groups of proteins may be regarded as hormones of the immune system.

Of note, cytokines also play a central role in the pathogenesis of many chronic inflammatory diseases. This includes allergic and autoimmune diseases, autism, chronic fatigue syndrome, fibromyalgia, Alzheimer’s disease, or conditions such as obesity, pain, etc.

The Cytokines of the Immune System offers a new approach, a combination of a detailed guidebook-style cytokine description, disease-linking and immunologic roles. In cataloguing cytokines, the book lists their potential for therapeutic use, links them to disease treatments needing further research and development, and shows their utility for learning about the immune system.

Key Features

  • Supplies new ideas for basic and clinical research
  • Provides cytokine descriptions in a guidebook-style, cataloging the origins, structures, functions, receptors, disease-linkage, and therapeutic potentials
  • Offers a textbook-style view on the immune system with the immunologic role of each cytokine

Chapters

  • Introduction—Common Features About Cytokines
  • The Immune System—Definition and Development of Immunity
  • Activation of Cells of the Immune System
  • The Role and Regulation of the Immune Responses
  • Cytokines of the Immune System: Interferons
  • Cytokines of the Immune System: Interleukins
  • Cytokines of the Immune System: Chemokines
  • Cytokines Important for Growth and/or Development of Cells of the Immune System
  • Theories about the Function of the Immune System

Readership

Graduate students to scientists, researchers, teachers in microbiology, immunology, biochemistry, cell biology, medicine, cytokine biology, and odontology: clinicians in all specialties of medicine and surgery: pharmaceutical companies and their R&D divisions.

Paperback: 320 pages; Publisher: Academic Press; 1 edition (June 16, 2015)


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amazon> The Cytokines of the Immune System: The Role of Cytokines in Disease Related to Immune Response

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Microglia: Gatekeepers for Neuropathic Pain http://www.brainimmune.com/microglia-gatekeepers-neuropathic-pain/ Wed, 08 Aug 2018 12:30:20 +0000 http://www.brainimmune.com/?p=6823 Overview article Introduction Where acute pain protects an individual from further damage, chronic pain serves no adaptive purpose. Approximately 1 in 5 people suffer from chronic pain, which exacts a substantial toll on the both the individual and on national economies (Gaskin and Richard, 2012; Nahin, 2015; Pizzo and Clark, 2012). Chronic pain can arise […]

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Overview article
Introduction

Where acute pain protects an individual from further damage, chronic pain serves no adaptive purpose. Approximately 1 in 5 people suffer from chronic pain, which exacts a substantial toll on the both the individual and on national economies (Gaskin and Richard, 2012; Nahin, 2015; Pizzo and Clark, 2012). Chronic pain can arise due to unresolved inflammation (e.g., rheumatoid arthritis), damage to the nervous system (neuropathic pain), and due to unknown precipitating factors (e.g., fibromyalgia). Specific injuries and diseases that can cause neuropathic pain include traumatic injury (e.g. spinal cord injury), stroke, herpes zoster infection (post-herpetic neuralgia), and multiple sclerosis.

A substantial literature has been devoted to understanding neuropathic pain. Basic science studies have revealed that there are key nervous systems sites for pain modulation. These include the site of injury, the cell bodies of primary afferents (dorsal root ganglia; DRG), the dorsal horn of the spinal cord, and a distributed group of brain regions known as the ‘pain matrix’ (Basbaum et al., 2009; Ossipov et al., 2010; Peirs and Seal, 2016; Wiech, 2016). Animal studies have predominantly focused on the spinal cord; this site has particular significance for pain, as primary afferent neurons synapse here with pain projection neurons, and are modulated by descending inhibitory neurons and interneurons (Ossipov et al., 2010; Peirs and Seal, 2016). Therefore, this site will be the focus of this review. Studies in spinal cord have revealed that neuropathic pain is not purely the product of dysfunctional neuronal communication, but that non-neuronal cells, such as microglia, are also critical participants (Grace et al., 2014; Ji et al., 2016).

What is the evidence for involvement of microglia in chronic pain?

Microglia are the resident macrophages of the central nervous system (CNS) and play a key role in maintaining homeostasis. Activation of spinal microglia in response to injury of peripheral nerves was first demonstrated in the late 1990s; immunohistochemical and gene expression studies revealed that microglial ‘activation’ markers were rapidly elevated (Colburn et al., 1997; Tanga et al., 2004). A causal role for microglia in the pain behaviors caused by peripheral nerve injury was then inferred when minocycline treatment was found to prevent pain in rats (Ledeboer et al., 2005a; Raghavendra et al., 2003). A key finding of these and subsequent studies (e.g. (Jin et al., 2003)) was that expression of microglia activation markers peaked within 2 weeks of injury, while inhibition of microglial signaling could prevent, but not reverse, neuropathic pain. This led to the conclusion that microglia participate in the development of neuropathic pain, but not its maintenance. A recent study using Mac1-saporin depletion has claimed that microglia do contribute to the maintenance of neuropathic pain, as their depletion reverses pain behaviors 3 months after nerve injury (Echeverry et al., 2017). However, the consensus view is that microglia are principally early responders to nerve injury.

A limitation to this early research is that pharmacological agents like minocycline also inhibit neurons and astrocytes; the lack of selectivity for microglia confounds interpretation. However, several studies have reinforced evidence for microglial participation in pain. Demonstrating sufficiency for pain, microglia were activated in vitro and then adoptively transferred to naïve male rats, inducing pain behaviors (Tsuda et al., 2003). We have recently expressed Designer Receptors Exclusively Activated by Designer Drugs (DREADDs) in spinal microglia, using a cell-selectively promoter (Grace et al., 2016, 2018). Activation of excitatory DREADDs in naïve male rats induced allodynia (sensitivity to innocuous stimuli), supportive of the sufficiency for microglia activation for pain. We also showed that inhibiting microglia with DREADDs could reverse neuropathic pain in males, which demonstrated that microglia are necessary for neuropathic pain.

There is emerging evidence that microglia may contribute to neuropathic pain in a sex-dependent manner. Acute depletion of microglia or inhibition with minocycline reversed neuropathic pain in male rats only (Sorge et al., 2015). However, these findings are not without controversy (Costigan et al., 2009; Krukowski et al., 2016), and additional studies with longer-term treatments are required; when neuropathic pain is fully developed, repeated treatments are often required for reversal. Nonetheless, the accumulating evidence for males-specific engagement of particular signaling pathways will be discussed.

How do microglia become activated after neuronal injury?

Given the evidence that microglia are important cellular mediators of neuropathic pain, investigators next turned to the question of how microglia can respond to nerve injury.

Microglial activation is understood as a change in cell number, morphology, phenotype and motility, the expression of membrane-bound and intracellular signaling proteins, and the release of immunoregulatory products, such as cytokines and chemokines. Microglia express a range of receptors that detect ligands released as a consequence of neuronal injury, and that lead to their activation.

ATP. Injured neurons release ATP in the dorsal horn of the spinal cord (Masuda et al., 2016), which is detected by purinergic receptors expressed by microglia; these include ionotropic P2X4 and P2X7 receptors, and metabotropic P2Y12 and P2Y13 receptors (Trang et al., 2012; Tsuda, 2017). Microglia upregulate surface expression of these receptors after peripheral nerve injury. Their involvement in neuropathic pain has been confirmed in genetic knockout and knockdown studies, as pain behaviors are reduced under these conditions (Sorge et al., 2012; Tsuda et al., 2003). However, the P2X4R pathway is specifically engaged in male rather than female rodents (Mapplebeck et al., 2018; Sorge et al., 2015). This may be due to differential transcriptional regulation of P2rx4 by the transcription factor IRF5 (Mapplebeck et al., 2018).

Chemokines. Several chemokines are produced and released by injured neurons. At present the strongest evidence supports a role for CSF-1. The cognate receptor CSF-1R is expressed exclusively by microglia in the CNS, and is essential for survival (Elmore et al., 2014). Peripheral nerve injury induces de novo expression of CSF-1 in the DRG (Guan et al., 2016). Conditional knockout of CSF-1 in sensory neurons prevented development of pain behaviors, and reduced microglial activation and proliferation in the spinal dorsal horn (Guan et al., 2016). There is evidence that engagement of this pathway may precede activation of microglia via ATP, as the CSF-1R adapter protein DAP12, is upstream of the P2X4R gene.

Other groups have previously suggested that the chemokines CCL2 and CX3CL1 are neuron-glia signals in neuropathic pain (Abbadie et al., 2003; Milligan et al., 2004). However, subsequent studies revealed that microglia express very low levels of CCR2 (Mizutani et al., 2012), suggesting a limited role for its ligand CCL2. While microglia uniquely express the receptor for CX3CL1 in the CNS (Mizutani et al., 2012), the release of this ligand from neurons is now known to be secondary to microglial activation; CX3CL1 is cleaved by cathepsin S derived from already activated microglia (Clark et al., 2009). Furthermore, DAP12 is also upstream of CX3CR1 and cathepsin S genes (Guan et al., 2016). Thus, CSF-1 appears to be the principal chemokine to mediate microglial activation after peripheral nerve injury.

Damage associated molecular patterns (DAMPs). According to the danger model of immunogenicity (Matzinger, 1994), the immune system can respond to cellular damage and the consequent release of DAMPs. Several DAMPs have been implicated in neuropathic pain, including High Mobility Group Box 1 (HMGB1), Heat shock proteins (HSP)-60 and -90, biglycan and fibrinogen (Lacagnina et al., 2018). These molecules are typically sequestered within intracellular compartments or the extracellular matrix, and become liberated into the extracellular milieu during stress or damage. It should be noted that the cellular source of many of these DAMPs has not been unequivocally demonstrated. Nonetheless, microglia respond to exogenous administration of DAMPs. Pattern recognition receptors are those capable of detecting such DAMPs, and among this receptor class, Toll-like receptors (TLRs) have been most thoroughly investigated (Lacagnina et al., 2018).

Of the 13 TLRs expressed in rodents, most research has focused on TLR4. TLR4 is upregulated after peripheral nerve injury. However, evidence for causal involvement in neuropathic pain comes from pharmacological and genetic manipulations: pain behaviors after nerve injury are attenuated when TLR4 or accessory proteins (required for signaling) are inhibited, knocked out, or knocked down (Hutchinson et al., 2008; Lacagnina et al., 2018; Tanga et al., 2005). There is an emerging role for other TLRs in neuropathic pain, including TLR2, 3, 5, and 9 (Lacagnina et al., 2018).

Finally, TLR4-dependent pain may be sexually dimorphic. Intrathecal injection of the TLR4 agonist LPS induces allodynia in male (but not female) rats (Sorge et al., 2011). This is in notable contrast to intrathecal disulfide HMGB1, which induces allodynia in both male and female mice (Agalave et al., 2014). Reversal of intrathecal LPS-evoked tactile allodynia by the small molecule TLR4 antagonist TAK-242 occurs in male mice, while having no effect on females (Woller et al., 2016) Similarly, male mice deficient in TLR4 do not develop robust neuropathic pain after peripheral nerve injury, whereas female mice do (Stokes et al., 2013). This leads to the intriguing possibility of sex differences regarding the involvement of innate immune signaling in the development of neuropathic tactile hypersensitivity. Given the predominance of chronic pain conditions disproportionately afflicting women, it has been argued that interactions between endocrine and immune mechanisms may help explain some of the sex differences observed in the epidemiology of pain disorders (Mogil and Bailey, 2010; Nicotra et al., 2014).

Intracellular signaling pathways. Many of the receptors described above converge on common intracellular signaling pathways, including activation of the transcription factor NFkB, and p38 and ERK mitogen activated protein kinases (MAPKs). Such activation occurs in spinal microglia after peripheral nerve injury, and leads increased transcription of proinflammatory and pronociceptive cytokines and growth factors (Jin et al., 2003; Ledeboer et al., 2005b; Zhuang et al., 2005). Other signaling pathways include activation of NADPH oxidase isoform 2 that generate reactive oxygen species (Kim et al., 2010). These enzymes and transcription factors are causal to neuropathic pain, as their inhibition or genetic deletion reverses pain behaviors evoked by peripheral nerve injury in male rodents. However, one group has assessed female rodents, and shown that pain behaviors are not reversed when p38 is inhibited (Sorge et al., 2015; Taves et al., 2016). This again points to a male-specific role for microglia in neuropathic pain.

How do activated microglia cause pain?

As noted above, a primary consequence of microglial activation is the release of proinflammatory cytokines, growth factors, and reactive oxygen species. These mediators act at central synapses in the spinal cord dorsal horn to disrupt the balance of excitatory and inhibitory neurotransmission.

Enhanced excitatory synaptic transmission. Cytokines such as TNF and IL-1b increase the excitatory tone of pain projection neurons by enhancing glutamate release and availability (Grace et al., 2014). For example, activation of IL-1 receptors that are functionally coupled to presynaptic NMDA receptors promotes glutamate exocytosis (Yan and Weng, 2013). Both IL-1b and TNF can downregulate transporters expressed by astrocytes that are responsible for uptake of glutamate (Xin et al., 2009; Yan et al., 2014); the consequence is excessive glutamate levels in the synaptic cleft. Cytokines and chemokines can also sensitize post-synaptic terminals. The mechanisms include increased trafficking and surface expression of AMPA receptors, and by phosphorylating NMDA receptor subunits (Gao et al., 2007; Stellwagen and Malenka, 2006; Stellwagen et al., 2005; Zhang et al., 2008). Collectively, these studies show that inflammatory mediators released by microglia have the capacity to facilitate hyperexcitability of pain projection neurons.

Reduced inhibitory synaptic transmission. Mediators derived from microglia can also cause disinhibition. Cytokines, chemokines and reactive oxygen species can diminish release of GABA and glycine from interneurons and descending inhibitory projections in the spinal cord (Gosselin et al., 2005; Kawasaki et al., 2008; Yowtak et al., 2011). Activated microglia also sculpt synaptic elements in the spinal dorsal horn and excessively prune GABAergic terminals (Batti et al., 2016). The growth factor BDNF activates TrkB receptors on postsynaptic terminals, reducing expression of the KCC2 potassium-chloride cotransporter (Coull et al., 2005). This leads to increased intracellular Cl concentrations that weaken GABA receptor mediated hyperpolarization. Only males exhibit BDNF-dependent neuropathic pain (Sorge et al., 2015); this result is consistent with BDNF release requiring P2X4 receptor and p38 MAPK activation, which themselves are activated in a sexually dimorphic manner (Mapplebeck et al., 2018; Taves et al., 2016). The consequence of these disinhibitory mechanisms is to increase the excitability of pain projection neurons.

Future directions and conclusions

A major challenge for the future is to translate the findings from animal models into humans. Imaging studies are yielding very promising results using radioligand binding to TSPO, a putative marker of glial activation. Binding was increased in thalamic nuclei, somatosensory cortices of patients with low back pain (Loggia et al., 2015), and the neuroforamina and spinal cords of patients with lumbar radiculopathy (Albrecht et al., 2018). Further work is required to understand the function of TSPO in neuropathic pain and to develop new radioligands. Firstly, it is unclear whether TSPO expression correlates with activation (Owen et al., 2017). Secondly, there is some evidence that TSPO has anti-inflammatory function (Lee et al., 2016), and thus only a subset of glia may be labelled. Which subset that may be, and its relationship to neuropathic pain, need to be defined. Finally, the selectivity of TSPO to microglia is a matter of debate that needs clarification (Crawshaw and Robertson, 2017). Nonetheless, these studies provide compelling evidence for the association of glial activation in human chronic pain states. PET imaging may also be a useful tool to validate target engagement for development of novel therapeutics that target microglia.

The vast majority of studies have focused on microglia in the spinal cord. However, the sensory and affective components of chronic pain are ultimately encoded in the brain, as noted above. Several groups, including my own, are now beginning the investigate how microglia in the brain contribute to the multi-dimensional experience of chronic pain (Grace and Lacagnina, 2018; Taylor et al., 2015).

The evidence summarized here highlights a critical role for microglia in the initiation of neuropathic pain, especially in male rodents. Given that women predominantly suffer with chronic pain, studies should now be directed towards identifying whether microglia are truly a relevant clinical target for treatment of chronic pain; dysfunctional synaptic plasticity induced by activated microglia is a promising therapeutic avenue for a disease that is poorly managed and causes untold suffering.

Author Affiliations:

Peter M. Grace, PhD – Department of Symptom Research, University of Texas MD Anderson Cancer Center, Houston, TX 77030; e: pgrace@mdanderson.org

List of Non-Standard Abbreviations


CNS, central nervous system; DRG, dorsal root ganglia; DREADDs, designer receptor exclusively activated by a designer drug; DAMP, damage associated molecular pattern; IL-1, interleukin-1; TLR, toll-like receptor; TNF, tumor necrosis factor.


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Lacagnina, M.J., Watkins, L.R., and Grace, P.M. (2018). Toll-like receptors and their role in persistent pain. Pharmacol. Ther. 184, 145–158.

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Ledeboer, A., Gamanos, M., Lai, W., Martin, D., Maier, S.F., Watkins, L.R., and Quan, N. (2005b). Involvement of spinal cord nuclear factor kappaB activation in rat models of proinflammatory cytokine-mediated pain facilitation. Eur. J. Neurosci. 22, 1977–1986.

Lee, J.-W., Nam, H., and Yu, S.-W. (2016). Systematic Analysis of Translocator Protein 18 kDa (TSPO) Ligands on Toll-like Receptors-mediated Pro-inflammatory Responses in Microglia and Astrocytes. Exp. Neurobiol. 25, 262–268.

Loggia, M.L., Chonde, D.B., Akeju, O., Arabasz, G., Catana, C., Edwards, R.R., Hill, E., Hsu, S., Izquierdo-Garcia, D., Ji, R.-R., et al. (2015). Evidence for brain glial activation in chronic pain patients. Brain J. Neurol. 138, 604–615.

Mapplebeck, J.C.S., Dalgarno, R., Tu, Y., Moriarty, O., Beggs, S., Kwok, C.H.T., Halievski, K., Assi, S., Mogil, J.S., Trang, T., et al. (2018). Microglial P2X4R-evoked pain hypersensitivity is sexually dimorphic in rats. Pain.

Masuda, T., Ozono, Y., Mikuriya, S., Kohro, Y., Tozaki-Saitoh, H., Iwatsuki, K., Uneyama, H., Ichikawa, R., Salter, M.W., Tsuda, M., et al. (2016). Dorsal horn neurons release extracellular ATP in a VNUT-dependent manner that underlies neuropathic pain. Nat. Commun. 7, 12529.

Matzinger, P. (1994). Tolerance, danger, and the extended family. Annu. Rev. Immunol. 12, 991–1045.

Milligan, E.D., Zapata, V., Chacur, M., Schoeniger, D., Biedenkapp, J., O’Connor, K.A., Verge, G.M., Chapman, G., Green, P., Foster, A.C., et al. (2004). Evidence that exogenous and endogenous fractalkine can induce spinal nociceptive facilitation in rats. Eur. J. Neurosci. 20, 2294–2302.

Mizutani, M., Pino, P.A., Saederup, N., Charo, I.F., Ransohoff, R.M., and Cardona, A.E. (2012). The fractalkine receptor but not CCR2 is present on microglia from embryonic development throughout adulthood. J. Immunol. 188, 29–36.

Mogil, J.S., and Bailey, A.L. (2010). Sex and gender differences in pain and analgesia. Prog. Brain Res. 186, 141–157.

Nahin, R.L. (2015). Estimates of pain prevalence and severity in adults: United States, 2012. J. Pain 16, 769–780.

Nicotra, L., Tuke, J., Grace, P.M., Rolan, P.E., and Hutchinson, M.R. (2014). Sex differences in mechanical allodynia: how can it be preclinically quantified and analyzed? Front. Behav. Neurosci. 8, 40.

Ossipov, M.H., Dussor, G.O., and Porreca, F. (2010). Central modulation of pain. J. Clin. Invest. 120, 3779–3787.

Owen, D.R., Narayan, N., Wells, L., Healy, L., Smyth, E., Rabiner, E.A., Galloway, D., Williams, J.B., Lehr, J., Mandhair, H., et al. (2017). Pro-inflammatory activation of primary microglia and macrophages increases 18 kDa translocator protein expression in rodents but not humans. J. Cereb. Blood Flow Metab. 37, 2679–2690.

Peirs, C., and Seal, R.P. (2016). Neural circuits for pain: Recent advances and current views. Science 354, 578–584.

Pizzo, P.A., and Clark, N.M. (2012). Alleviating suffering 101–pain relief in the United States. N. Engl. J. Med. 366, 197–199.

Raghavendra, V., Tanga, F., and DeLeo, J.A. (2003). Inhibition of microglial activation attenuates the development but not existing hypersensitivity in a rat model of neuropathy. J. Pharmacol. Exp. Ther. 306, 624–630.

Sorge, R.E., LaCroix-Fralish, M.L., Tuttle, A.H., Sotocinal, S.G., Austin, J.-S., Ritchie, J., Chanda, M.L., Graham, A.C., Topham, L., Beggs, S., et al. (2011). Spinal cord Toll-like receptor 4 mediates inflammatory and neuropathic hypersensitivity in male but not female mice. J. Neurosci. 31, 15450–15454.

Sorge, R.E., Trang, T., Dorfman, R., Smith, S.B., Beggs, S., Ritchie, J., Austin, J.-S., Zaykin, D.V., Vander Meulen, H., Costigan, M., et al. (2012). Genetically determined P2X7 receptor pore formation regulates variability in chronic pain sensitivity. Nat. Med. 18, 595–599.

Sorge, R.E., Mapplebeck, J.C.S., Rosen, S., Beggs, S., Taves, S., Alexander, J.K., Martin, L.J., Austin, J.-S., Sotocinal, S.G., Chen, D., et al. (2015). Different immune cells mediate mechanical pain hypersensitivity in male and female mice. Nat. Neurosci. 18, 1081–1083.

Stellwagen, D., and Malenka, R.C. (2006). Synaptic scaling mediated by glial TNF-alpha. Nature 440, 1054–1059.

Stellwagen, D., Beattie, E.C., Seo, J.Y., and Malenka, R.C. (2005). Differential regulation of AMPA receptor and GABA receptor trafficking by tumor necrosis factor-alpha. J. Neurosci. 25, 3219–3228.

Stokes, J.A., Cheung, J., Eddinger, K., Corr, M., and Yaksh, T.L. (2013). Toll-like receptor signaling adapter proteins govern spread of neuropathic pain and recovery following nerve injury in male mice. J. Neuroinflammation 10, 148.

Tanga, F.Y., Raghavendra, V., and DeLeo, J.A. (2004). Quantitative real-time RT-PCR assessment of spinal microglial and astrocytic activation markers in a rat model of neuropathic pain. Neurochem. Int. 45, 397–407.

Tanga, F.Y., Nutile-McMenemy, N., and DeLeo, J.A. (2005). The CNS role of Toll-like receptor 4 in innate neuroimmunity and painful neuropathy. Proc. Natl. Acad. Sci. U. S. A. 102, 5856–5861.

Taves, S., Berta, T., Liu, D.-L., Gan, S., Chen, G., Kim, Y.H., Van de Ven, T., Laufer, S., and Ji, R.-R. (2016). Spinal inhibition of p38 MAP kinase reduces inflammatory and neuropathic pain in male but not female mice: Sex-dependent microglial signaling in the spinal cord. Brain. Behav. Immun. 55, 70–81.

Taylor, A.M.W., Castonguay, A., Taylor, A.J., Murphy, N.P., Ghogha, A., Cook, C., Xue, L., Olmstead, M.C., De Koninck, Y., Evans, C.J., et al. (2015). Microglia disrupt mesolimbic reward circuitry in chronic pain. J. Neurosci. 35, 8442–8450.

Trang, T., Beggs, S., and Salter, M.W. (2012). ATP receptors gate microglia signaling in neuropathic pain. Exp. Neurol. 234, 354–361.

Tsuda, M. (2017). P2 receptors, microglial cytokines and chemokines, and neuropathic pain. J. Neurosci. Res. 95, 1319–1329.

Tsuda, M., Shigemoto-Mogami, Y., Koizumi, S., Mizokoshi, A., Kohsaka, S., Salter, M.W., and Inoue, K. (2003). P2X4 receptors induced in spinal microglia gate tactile allodynia after nerve injury. Nature 424, 778–783.

Wiech, K. (2016). Deconstructing the sensation of pain: The influence of cognitive processes on pain perception. Science 354, 584–587.

Woller, S.A., Ravula, S.B., Tucci, F.C., Beaton, G., Corr, M., Isseroff, R.R., Soulika, A.M., Chigbrow, M., Eddinger, K.A., and Yaksh, T.L. (2016). Systemic TAK-242 prevents intrathecal LPS evoked hyperalgesia in male, but not female mice and prevents delayed allodynia following intraplantar formalin in both male and female mice: The role of TLR4 in the evolution of a persistent pain state. Brain. Behav. Immun. 56, 271–280.

Xin, W.-J., Weng, H.-R., and Dougherty, P.M. (2009). Plasticity in expression of the glutamate transporters GLT-1 and GLAST in spinal dorsal horn glial cells following partial sciatic nerve ligation. Mol. Pain 5, 15.

Yan, X., and Weng, H.-R. (2013). Endogenous interleukin-1β in neuropathic rats enhances glutamate release from the primary afferents in the spinal dorsal horn through coupling with presynaptic N-methyl-D-aspartic acid receptors. J. Biol. Chem. 288, 30544–30557.

Yan, X., Yadav, R., Gao, M., and Weng, H.-R. (2014). Interleukin-1 beta enhances endocytosis of glial glutamate transporters in the spinal dorsal horn through activating protein kinase C. Glia 62, 1093–1109.

Yowtak, J., Lee, K.Y., Kim, H.Y., Wang, J., Kim, H.K., Chung, K., and Chung, J.M. (2011). Reactive oxygen species contribute to neuropathic pain by reducing spinal GABA release. Pain 152, 844–852.

Zhang, R.-X., Li, A., Liu, B., Wang, L., Ren, K., Zhang, H., Berman, B.M., and Lao, L. (2008). IL-1ra alleviates inflammatory hyperalgesia through preventing phosphorylation of NMDA receptor NR-1 subunit in rats. Pain 135, 232–239.

Zhuang, Z.-Y., Gerner, P., Woolf, C.J., and Ji, R.-R. (2005). ERK is sequentially activated in neurons, microglia, and astrocytes by spinal nerve ligation and contributes to mechanical allodynia in this neuropathic pain model. Pain 114, 149–159.

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Cytokines, Stress, and Depression (reprint of the 1st ed) http://www.brainimmune.com/cytokines-stress-depression/ Tue, 07 Aug 2018 13:09:17 +0000 http://www.brainimmune.com/?p=6820 Cytokines, Stress, and Depression (Advances in Experimental Medicine and Biology) is devoted to the establishment of a link between cytokines and clinical depression. Cytokines, Stress, and Depression is published by Springer and edited by Robert Dantzer, Emmanuelle E. Wollmann and Raz Yirmiya. It is based on the proceedings of a meeting that took place in […]

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Cytokines, Stress, and DepressionCytokines, Stress, and Depression (Advances in Experimental Medicine and Biology) is devoted to the establishment of a link between cytokines and clinical depression.

Cytokines, Stress, and Depression is published by Springer and edited by Robert Dantzer, Emmanuelle E. Wollmann and Raz Yirmiya. It is based on the proceedings of a meeting that took place in Roscoff, France, on May 14–17, 1998. The purpose of the meeting, as stated in the preface was to bring together scientists working in the field to discuss “the converging evidence between the brain effects of cytokines and the immunological correlates of depression.”

Cytokines, the chemical messengers between immune cells play a key role in mediating inflammatory and immune responses. These diverse groups of proteins may be regarded as hormones of the immune system that control the proliferation, differentiation and activity of immune cells. Evidence accumulated over the last 2-3 decades indicates that cytokines are major players in the pathogenesis of atopic/allergic and autoimmune diseases, obesity and atherosclerosis, autism, chronic fatigue syndrome (CFS), fibromyalgia, Alzheimer’s disease, etc.

The rapid pace of ‘discovery’ of newer cytokines and the broader role they were found to play among immune cells led to a new terminology that assigns an ‘interleukin’ number to cytokines as their genes are sequenced. Little did anybody know at the time that these cytokines had anything to do with the brain or behavior?

Recent evidence, however, indicates that pro-inflammatory cytokines contribute to the pathogenesis of depression. Thus, treatment of patients with chronic hepatitis C and malignant melanoma with high doses of INF-α is often accompanied by symptoms of depression. Another major link with inflammatory states is the greatly increased incidence of depression in individuals suffering from chronic inflammatory disorders. An additional link with inflammatory states and cytokines, is the increased level of pro-inflammatory cytokines, such as IL-6 in subjects with depressive symptoms and syndromes.

In the Cytokines, Stress, and Depression the evidence for a cytokine connection in depressive illness as presented in this book is overwhelming: cytokines are associated with vegetative signs of depression; treatment with cytokines produces depressed mood and altered cognition; cytokine production is affected by stress; cytokines are associated with increased activity of the hypothalamic-pituitary-adrenal axis and dysregulation of neurotransmitter metabolism; antidepressant treatment affects cytokine secretion; and so on.

Few selected chapters of Cytokines, Stress, and Depression are listed below:


  • Major Depression and Activation of The Inflammatory Response System
  • Cytokine Production in Depressed Patients
  • Mood and Cognitive Disorders in Cancer Patients Receiving Cytokine Therapy
  • Mechanisms of the Behavioural Effects of Cytokines
  • Effects of Cytokines on Glucocorticoid Receptor Expression And Function
  • Effects of Cytokines on Cerebral Neurotransmission
  • Inflammation and Brain Function under Basal Conditions and During Long-Term Elevation of Brain Corticotropin-Releasing Hormone Levels
  • Dynamic Regulation of Proinflammatory Cytokines
  • Anhedonic and Anxiogenic Effects of Cytokine Exposure
  • Stress, Depression, and The Role of Cytokines
  • Cytokines, “Depression Due to A General Medical Condition,” and Antidepressant Drugs
  • Cytokines, Stress, and Depression

Series: Advances in Experimental Medicine and Biology (Book 461); Paperback: 338 pages; Publisher: Springer; Softcover reprint of the original 1st ed. 1999 edition (March 23, 2013)

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Glucocorticoid Signaling: From Molecules to Mice to Man http://www.brainimmune.com/glucocorticoid-signaling-from-molecules-to-mice-to-man/ Mon, 06 Aug 2018 13:58:53 +0000 http://www.brainimmune.com/?p=6816 Glucocorticoid Signaling: From Molecules to Mice to Man (Advances in Experimental Medicine and Biology) is published by Springer and edited by Jen-Chywan Wang and Charles Harris. Glucocorticoids, the steroid hormones secreted from the adrenal cortex zona fasciculate play numerous important roles in the maintenance of internal homeostasis by influencing activities of virtually all organs and […]

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glucorticoid signaling bookGlucocorticoid Signaling: From Molecules to Mice to Man (Advances in Experimental Medicine and Biology) is published by Springer and edited by Jen-Chywan Wang and Charles Harris.

Glucocorticoids, the steroid hormones secreted from the adrenal cortex zona fasciculate play numerous important roles in the maintenance of internal homeostasis by influencing activities of virtually all organs and tissues. Of note, glucocorticoids are essential in the body’s response to stress, and a complex but organized feedback system, called the hypothalamic-pituitary adrenal (HPA) axis, regulates the production of glucocorticoids.

Glucocorticoid Signaling: From Molecules to Mice to Man provides a comprehensive overview of glucocorticoids and their role in regulating many aspects of physiology and their use in the treatment of disease.

This recent book is broken into four sections that begin by giving a general introduction to glucocorticoids and a brief history of the field. The second section will discuss the effects of glucocorticoids on metabolism, while the third section will cover the effects of glucocorticoids on key tissues.

The final section will discuss general topics, such as animal models in glucocorticoid research and clinical implications of glucocorticoid research. Featuring chapters from leaders in the field, this volume will be of interest to both researchers and clinicians.

Chapters:


  • Regulatory Actions of Glucocorticoid Hormones: From Organisms to Mechanisms

  • Molecular Biology of Glucocorticoid Signaling
  • Mechanisms of Glucocorticoid-Regulated Gene Transcription
  • Clinical Perspective: What Do Addison and Cushing Tell Us About Glucocorticoid Action?
  • Regulation of Glucose Homeostasis by Glucocorticoids
  • How Do Glucocorticoids Regulate Lipid Metabolism?
  • Glucocorticoids and Skeletal Muscle
  • Glucocorticoid-Induced Osteoporosis
  • Effects of Glucocorticoids in the Immune System
  • Glucocorticoids and the Brain: Neural Mechanisms Regulating the Stress Response
  • Glucocorticoid Regulation of Reproduction
  • Glucocorticoids and the Lung
  • Glucocorticoids and the Cardiovascular System
  • Glucocorticoids and Cancer
  • Animal Models of Altered Glucocorticoid Signaling
  • The Dehydrogenase Hypothesis
  • Conclusions and Future Directions

Series: Advances in Experimental Medicine and Biology (Book 872); Hardcover: 385 pages; Publisher: Springer; 1st ed. 2015 edition (July 28, 2015).

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Hormone Imbalance Syndrome: America’s Silent Plague: Uncovering the Roots of the Obesity Epidemic and Most Common Diseases http://www.brainimmune.com/hormone-imbalance-syndrome-americas-silent-plague/ Sat, 28 Jul 2018 15:17:09 +0000 http://www.brainimmune.com/?p=6768 Hormone Imbalance Syndrome: America’s Silent Plague: Uncovering the Roots of the Obesity Epidemic and Most Common Diseases is written by Benoit Tano MD PhD, and published by Integrative Medical Press. Dr. Tano is the founder of Integrative Immunity Health System, PC located in Edina, Minnesota. Dr. Tano is certified by the American Board of Internal […]

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Hormone Imbalance Syndrome America's Silent PlagueHormone Imbalance Syndrome: America’s Silent Plague: Uncovering the Roots of the Obesity Epidemic and Most Common Diseases is written by Benoit Tano MD PhD, and published by Integrative Medical Press.

Dr. Tano is the founder of Integrative Immunity Health System, PC located in Edina, Minnesota. Dr. Tano is certified by the American Board of Internal Medicine and the American Board of Allergy and Immunology, and is Johns Hopkins-fellowship trained in allergy and clinical immunology.

In the U.S., as per CDC more than one-third of adults are obese, whereas 17.1% of U.S. children are now obese, and overall, up to 2/3 of children and adolescents in the United States are overweight or obese (c.f. JAMA, 2006,  295, 1549).

In Europe (before Brexit), and as per Wikipedia and Forbes, United Kingdom has the most overweight population, with 22% of Britons now obese.

Thus, many people today are suffering increasingly from obesity and obesity related diseases, and they are confused about why this is the case and worried that they don’t know what to do to feel better.

Do you or someone you know suffer from obesity or obesity related conditions? Are you tired of being blamed for too much calorie intake without much of calorie expenditure? Are you tired of hearing you should eat right, exercise and lose weight without any clear plans to help you figure out the true cause of your obesity? Do you live in the South, the Midwest or the Upper Midwest of the US?

Do you know that obesity is more concentrated in these regions than in the Northeast and the West? What is making the middle of America more obese? Have you struggled to find a treatment that really works and have been frustrated that you have only been offered fad diets? Don’t suffer through your condition unnecessarily.

Find out what is causing the American obesity epidemic and protect yourself and your family. Hormone Imbalance Syndrome: America’s Silent Plague answers these questions for you.

Print Length: 520 pages; Publisher: Integrative Medical Press; 1.0 edition (April 29, 2013)


Related stories you may like: Stress, the Reward System and the Epidemic of Obesity
Perfectionism: A Disease Risk Factor Just as Obesity and Smoking?


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amazon> Hormone Imbalance Syndrome: America’s Silent Plague Paperback – January 5, 2012

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Sex Hormones and Immunity to Infection http://www.brainimmune.com/sex-hormones-immunity-infection/ Mon, 23 Jul 2018 11:27:45 +0000 http://www.brainimmune.com/?p=6758 Sex Hormones and Immunity to Infection, edited by Sabra L. Klein and Craig Roberts and published by Springer, critically reviews the evolutionary origin and the functional mechanisms responsible for sexual dimorphism in response to infection. Recent research suggests that sex hormones regulate immune responses in vivo. Thus, estrogens and testosterone regulate humoral immune responses i.e. […]

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Sex Hormones Immunity to InfectionSex Hormones and Immunity to Infection, edited by Sabra L. Klein and Craig Roberts and published by Springer, critically reviews the evolutionary origin and the functional mechanisms responsible for sexual dimorphism in response to infection.

Recent research suggests that sex hormones regulate immune responses in vivo. Thus, estrogens and testosterone regulate humoral immune responses i.e. (auto)antibody production; where estrogen increases, while testosterone decreases antibody production. Sex hormones also regulate cellular immunity, by affecting T lymphocytes, including T cell proliferation and cytotoxicity and T helper(Th) 1 and Th2 cellular responses.

In contrast to autoimmunity where females display an increased incidence of autoimmune diseases, the prevalence and intensity of infection typically is higher in males than females and may reflect differences in exposure as well as susceptibility to pathogens. Elevated immunity among females is a double-edged sword in which it is beneficial against infectious diseases but is detrimental in terms of increased development of autoimmune diseases.

The book emphasizes the value of examining responses in both males and females to improve our understanding about host-pathogen interactions in both sexes. Sex Hormones and Immunity to Infection aims at bringing insight to the treatment and management of infectious diseases; it delineates areas where knowledge is lacking and highlights future avenues of research.

The contributors of Sex Hormones and Immunity to Infection are experts in their specific disciplines which range from microbiology and immunology to genetics, pathology, and evolutionary biology.

Chapters:

  • Sex Differences in Susceptibility to Infection: An Evolutionary Perspective
  • Effects of Sex Steroids on Innate and Adaptive Immunity
  • Sex Steroid Receptors in Immune Cells
  • Sex Differences in Susceptibility to Viral Infection
  • Sex Differences in Innate Immune Responses to Bacterial Pathogens
  • Sex Hormones and Regulation of Host Responses Against Parasites
  • Sex Differences in Parasitic Infections: Beyond the Dogma of Female-Biased Resistance
  • Progesterone, Pregnancy, and Innate Immunity
  • Pregnancy and Susceptibility to Parasites
  • Sex Steroids and Risk of Female Genital Tract Infection
  • Sex, Pregnancy and Measles

Hardcover: 332 pages; Publisher: Springer; 2010 ed. edition (13 Nov. 2009)


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The Wisdom of the Body http://www.brainimmune.com/wisdom-of-the-body/ Sat, 30 Jun 2018 16:43:14 +0000 http://www.brainimmune.com/?p=6647 The Wisdom of the Body, the revised and enlarged edition was published by W. W. Norton & Company (April 17, 1963, shown on the left) but the first, original version was published in 1932, once again by W.W. Norton & Company (shown below, on the right). This classic medical book was written by Walter Cannon, […]

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The Wisdom of the Body BrainImmuneThe Wisdom of the Body, the revised and enlarged edition was published by W. W. Norton & Company (April 17, 1963, shown on the left) but the first, original version was published in 1932, once again by W.W. Norton & Company (shown below, on the right).

This classic medical book was written by Walter Cannon, an American physician-scientist and physiologist, who introduced the concepts of homeostasis, fight-or-flight responses, and the sympathoadrenal system.

In The Wisdom of the Body, the dynamic equilibrium/steady state of the internal milieu or homeostasis is the central theme and Walter Cannon popularized this new term in his book.

According to Cannon when the body’s homeostasis is threaten the sympathoadrenal system is activated. The result of such stimulation is an increase in heart rate, constriction of blood vessels, and dilation of bronchioles, which allows the aroused organism to confront or flee the danger – the reaction, which is now well-known as the fight-or-flight response.

Cannon believed that the sympathoadrenal system plays a key role in returning the body to its normal state of equilibrium after such arousal had occurred.

Reviews:

“Cannon’s writing is clear and yet detailed, easily accessible to scientists and the lay public alike, and current findings and concepts of the time are summarized elegantly. His overarching point is that the human, characteristic of all mammals, relies less on an attempt to match his physiology with the external environment than to regulate his internal environment within narrow limits.

The Wisdom of the Body cover 1932

The Wisdom of the Body, the first, original edition, 1932; Provenance; from the library of Dr. Michael Jefferson with his bookplate; includes a SIGNED and inscribed presentation bookplate from the author, Walter B. Cannon M.D., Sc.D., Ll.D. From amazon.co.uk (public domain).

What Bernard refers to as the milieu interieur, Cannon calls the “fluid matrix.” Discussing how this fluid matrix and its integrity is maintained, he reviews current research, his own and others’, in the areas of thirst and hunger, water content of the blood, salt content, blood sugar/proteins/fat/calcium, oxygen supply, ph neutrality, and body temperature.

He also discusses the aging of homeostatic mechanisms over time before embarking on natural defenses of the organism and the margin of safety in bodily structures and function. His penultimate subject is “the two grand divisions of the nervous system” with particular attention to the role of the sympathetic (“sympathico-adrenal”) nervous system in homeostasis. After summarizing this entire discussion, Cannon provides a brief epilogue exploring possible relationships or parallels between biological and social homeostasis, an exploration heavily influenced by social theory of his time.

This is a fascinating and articulate presentation of fundamental understandings of human biology that have provided the foundation for subsequent medical research over the past eighty years.”

– Bruce, The Wisdom of the Body, Walter Bradford Cannon; goodreads.com

Paperback: 340 pages; Publisher: W. W. Norton & Company; Rev. and Enl. Ed edition (April 17, 1963)


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The Wisdom Of The Body

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Neuroimmune Pharmacology 2nd Edition http://www.brainimmune.com/neuroimmune-pharmacology-2nd-edition/ Mon, 18 Jun 2018 11:55:55 +0000 http://www.brainimmune.com/?p=6507 Neuroimmune pharmacology is a relatively young discipline, however well-grounded on interdisciplinary basic and translational research in pharmacology, immunology and neuroscience, aiming at the therapeutic exploitation of the rapidly growing knowledge about physiology and pathology of nervous system-immune system interconnections. The Society on Neuroimmune Pharmacology was founded in1993, while the first issue of the Journal of […]

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Neuroimmune Pharmacology 2nd EditionNeuroimmune pharmacology is a relatively young discipline, however well-grounded on interdisciplinary basic and translational research in pharmacology, immunology and neuroscience, aiming at the therapeutic exploitation of the rapidly growing knowledge about physiology and pathology of nervous system-immune system interconnections. The Society on Neuroimmune Pharmacology was founded in1993, while the first issue of the Journal of Neuroimmune Pharmacology was published in March 2006.

The 2nd edition of Neuroimmune Pharmacology by Howard E. Gendelman and Tsuneya Ikezu (Editors) with Serge Przedborski, Eliezer Masliah and Marco Cosentino (Associate Editors) has been published in 2017, nearly 9 years after the 1st edition.

With more than one thousand pages (two hundred pages more than the previous edition), Neuroimmune Pharmacology provides a comprehensive and cutting edge picture of the tremendous progresses achieved in the understanding of the mutual interconnections among inflammation, immunity and neural control of disease, in the central nervous system as well as in periphery.

Take just Parkinson’s disease (PD) as an example. Up to only a few years ago, investigating the role of inflammation and peripheral immunity in PD would have been considered unreasonable by most neuroscientists and immunologists. At present however PD-associated neurodegeneration as a consequence of neuroinflammation in turn supported by peripheral T cells likely activated by peripheral leakage of a-synuclein is much more than a simple speculation, and innovative therapeutics targeting inflammation and immunity increasingly represent promising opportunities for PD patients.

New developments in PD, as well as in multiple sclerosis, Alzheimer’s disease, amyotrophic lateral sclerosis, Huntington’s disease, prion disease, HIV, drugs of abuse, autism spectrum disorders and many others are extensively discussed together with novel and emerging therapeutic strategies, including immunotherapies for neurodegenerative disorders, polymer nanomaterials for drug delivery in the central nervous system, gene therapy and vaccination.

With 56 chapters authored by prominent experts in their respective fields, Neuroimmune Pharmacology is organized into three parts, dedicated to Immunology of the Nervous System, Immunology of Neurodegenerative, Neuroinflammatory, Neuroinfectious and Neuropsychiatric Disorders, and Therapies and Diagnostics.

As a whole, the book is a standalone reference for preclinical and clinical researchers as well as for clinicians searching for a guidance into the rapidly developing interdisciplinary field of neuroimmune pharmacology.

Few selected chapters of Neuroimmune Pharmacology are listed below:

  • Hippocampus, Spatial Memory and Neuroimmunomodulation
  • Immune Sensors and Effectors of Health and Disease
  • Stem Cells and Neurogenesis for Brain Development, Degeneration and Therapy
  • Growth and Neurotrophic Factors in HIV-Associated Neurocognitive Disorders
  • Neurodegeneration
  • HIV-Associated Neurocognitive Disorders
  • Neuroimmunomodulation of Human T-Lymphotrophic Virus Type I/II Infection
  • Alzheimer’s Disease
  • Neurogenesis and Brain Repair
  • The Neuroimmune System in Psychiatric Disorders
  • Therapeutic Strategies in Neurodegenerative Diseases
  • Therapeutic Considerations in HIV-Associated Neurocognitive Disorders

Hardcover: 1035 pages; Publisher: Springer; 2nd ed. 2017 edition (December 23, 2016)


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Neuroimmune Pharmacology

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