Effects on the Behavior and Neuroimmunity of Pulsed Microwaves with Different Peak Densities

Pulsed microwaves are widely used inradar,navigation, and communication. The average power density is low at narrow pulse widths or large pulse intervals,but pulsed microwaves at certain peak densities exert numerous biological effects, including

The Relationship Between Neuroimmunity and Bipolar Disorder:Mechanism and Translational Application

Neuroimmune system may be involved in the pathological process of bipolar disorder(BD),but the essential association is not fully understood.Accumulating evidence has shown that BD involves the activation of immune cells and the release of inflammatory substances in the central nerve system(CNS).Meanwhile,neuroimmune responses also interact with other hypothesis of the etiology of BD that are widely recognized,such as neurotransmitter systems,neuroendocrine systems,neurotrophic factors,and oxidative stress.Simultaneously,related genes and immune changes in peripheral blood vary with it.Overall,neuroimmunity may play an important role in the pathogenesis of BD,and the inflammatory cytokines,especially interleukin-6 and tumor necrosis factor-alpha,have potential value for the clinical diagnosis and prognosis of BD,as well as predicting the therapeutic effects of drugs.Large-scale studies are needed to extend the evidence on neuroimmunity in BD,and to examine its clinical value for applications such as early prediction and treatment.

Immunomodulation of enteric neural function in irritable bowel syndrome

Irritable bowel syndrome(IBS) is a common functional gastrointestinal disorder which is characterised by symptoms such as bloating, altered bowel habit and visceral pain. It's generally accepted that miscommunication between the brain and gut underlies the changes in motility, absorpto-secretory functionand pain sensitivity associated with IBS. However, partly due to the lack of disease-defining biomarkers, understanding the aetiology of this complex and multifactorial disease remains elusive. Anecdotally, IBS patients have noted that periods of stress can result in symptom flares and many patients exhibit comorbid stress-related mood disorders such as anxiety and depression. However, in addition to psychosocial stressors, infection-related stress has also been linked with the initiation, persistence and severity of symptom flares. Indeed, prior gastrointestinal infection is one of the strongest predictors of developing IBS. Despite a lack of overt morphological inflammation, the importance of immune factors in the pathophysiology of IBS is gaining acceptance. Subtle changes in the numbers of mucosal immune cell infiltrates and elevated levels of circulating pro-inflammatory cytokines have been reproducibly demonstrated in IBS populations. Moreover, these immune mediators directly affect neural signalling. An exciting new area of research is the role of luminal microbiota in the modulation of neuro-immune signalling, resulting in local changes in gastrointestinal function and alterations in central neural functioning. Progress in this area has begun to unravel some of the complexities of neuroimmune and neuroendocrine interactions and how these molecular exchanges contribute to GI

Regulation of neuroimmune processes by damage-and resolution-associated molecular patterns

Sterile inflammatory processes are essential for the maintenance of central nervous system homeostasis,but they also contribute to various neurological disorders,including neurotrauma,stroke,and demyelinating or neurodegenerative diseases.Immune mechanisms in the central nervous system and periphery are regulated by a diverse group of endogenous proteins,which can be broadly divided into the pro-inflammatory damageassociated molecular patterns(DAMPs)and anti-inflammatory resolution-associated molecular patterns(RAMPs),even though there is notable overlap between the DAMPand RAMP-like activities for some of these molecules.Both groups of molecular patterns were initially described in peripheral immune processes and pathologies;however,it is now evident that at least some,if not all,of these immunomodulators also regulate neuroimmune processes and contribute to neuroinflammation in diverse central nervous system disorders.The review of recent literature demonstrates that studies on DAMPs and RAMPs of the central nervous system still lag behind the much broader research effort focused on their peripheral counterparts.Nevertheless,this review also reveals that over the last five years,significant advances have been made in our understanding of the neuroimmune functions of several well-established DAMPs,including high-mobility group box 1 protein and interleukin 33.Novel neuroimmune functions have been demonstrated for other DAMPs that previously were considered almost exclusively as peripheral immune regulators;they include mitochondrial transcription factor A and cytochrome C.RAMPs of the central nervous system are an emerging area of neuroimmunology with very high translational potential since some of these molecules have already been used in preclinical and clinical studies as candidate therapeutic agents for inflammatory conditions,such as multiple sclerosis and rheumatoid arthritis.The therapeutic potential of DAMP antagonists and neutralizing antibodies in central nervous system neuroinflammatory diseases is also supported by several of the identified studies.It can be concluded that further studies of DAMPs and RAMPs of the central nervous system will continue to be an important and productive field of neuroimmunology.

Ambiguous nucleus regulates the proliferation and percentage of T lymphocytes in peripheral blood

The aim of this study was to examine the immunomodulatory role of the unilateral ambiguous nucleus （Amb）. We performed electrical stimulation of the unilateral Amb, electrical stimulation of the left parietal cortex and the lateral hypothalamus following unilateral Arab lesion, as well as microinjection of acetylcholine chloride and hemicholine-3 into the unilateral Amb, and electrical stimulation of the unilateral Amb after injection of atropine, mecamylamine, propranolol, and phentolamine. Results showed that the number and proliferation of peripheral blood T lymphocytes were increased after electrical stimulation of the unilateral Arab. The cholinergic neurons in the Amb released choline substances to alter cellular immunity, thus confirming that the Amb mediates the neuro-immunomodulatory process.

Neuroimmune crosstalk through brain-derived neurotrophic factor and its precursor pro-BDNF: New insights into mood disorders

Mood disorders are the most common mental disorders, affecting approximately350 million people globally. Recent studies have shown that neuroimmuneinteraction regulates mood disorders. Brain-derived neurotrophic factor (BDNF)and its precursor pro-BDNF, are involved in the neuroimmune crosstalk duringthe development of mood disorders. BDNF is implicated in the pathophysiologyof psychiatric and neurological disorders especially in antidepressant pharmacotherapy.In this review, we describe the functions of BDNF/pro-BDNF signalingin the central nervous system in the context of mood disorders. In addition, wesummarize the developments for BDNF and pro-BDNF functions in mooddisorders. This review aims to provide new insights into the impact ofneuroimmune interaction on mood disorders and reveal a new basis for furtherdevelopment of diagnostic targets and mood disorders.

Neuroimmune connections between corticotropinreleasing hormone and mast cells:novel strategies for the treatment of neurodegenerative diseases

Corticotropin-releasing hormone is a critical component of the hypothalamic–pituitary–adrenal axis,which plays a major role in the body’s immune response to stress.Mast cells are both sensors and effectors in the interaction between the nervous and immune systems.As first responders to stress,mast cells can initiate,amplify and prolong neuroimmune responses upon activation.Corticotropin-releasing hormone plays a pivotal role in triggering stress responses and related diseases by acting on its receptors in mast cells.Corticotropin-releasing hormone can stimulate mast cell activation,influence the activation of immune cells by peripheral nerves and modulate neuroimmune interactions.The latest evidence shows that the release of corticotropin-releasing hormone induces the degranulation of mast cells under stress conditions,leading to disruption of the bloodbrain barrier,which plays an important role in neurological diseases,such as Alzheimer’s disease,Parkinson’s disease,multiple sclerosis,autism spectrum disorder and amyotrophic lateral sclerosis.Recent studies suggest that stress increases intestinal permeability and disrupts the blood-brain barrier through corticotropin-releasing hormone-mediated activation of mast cells,providing new insight into the complex interplay between the brain and gastrointestinal tract.The neuroimmune target of mast cells is the site at which the corticotropin-releasing hormone directly participates in the inflammatory responses of nerve terminals.In this review,we focus on the neuroimmune connections between corticotropin-releasing hormone and mast cells,with the aim of providing novel potential therapeutic targets for inflammatory,autoimmune and nervous system diseases.

Role of Neuroimmune Interactions in COVID-19-related Cardiovascular Damage

Coronavirus disease 2019(COVID-19)has caused a global pandemic impacting over 200 countries/regions and more than 200 million patients worldwide.Among the infected patients,there is a high prevalence of COVID-19-related cardiovascular injuries.However,the specific mechanisms linking cardiovascular damage and COVID-19 remain unclear.The COVID-19 pandemic also has exacerbated the mental health burden of humans.Considering the close association between neuroimmune interactions and cardiovascular disease,this review assessed the complex pathophysiological mechanisms connecting neuroimmune interactions and cardiovascular disease.It was revealed that the mental health burden might be a pivotal accomplice causing COVID-19-associated cardiovascular damage.Specifically,the proinflammatory status of patients with a terrible mood state is closely related to overdrive of the hypothalamus-pituitary-adrenal(HPA)axis,sympathovagal imbalance,and endothelial dysfunction,which lead to an increased risk of developing cardiovascular injury during COVID-19.Therefore,during the prevention and treatment of cardiovascular complications in COVID-19 patients,particular attention should be given to relieve the mental health burden of these patients.

Reduced paraoxonase 1 activities may explain the comorbidities between temporal lobe epilepsy and depression,anxiety and psychosis

BACKGROUND Temporal lobe epilepsy(TLE)is the most common focal epilepsy subtype in adults and is frequently accompanied by depression,anxiety and psychosis.Aberrations in total paraoxonase 1(PON1)status may occur in TLE and these psychiatric conditions.AIM To examine PON1 status,namely Q192R PON1 genotypes and PON1 enzymatic activities,in TLE.METHODS We recruited 40 normal controls and 104 TLE patients,27 without comorbidities and 77 with comorbidities including mood disorders(n=25),anxiety disorders(n=27)and psychosis(n=25).RESULTS Four-(chloromethyl)phenyl acetate hydrolysis(CMPAase)and arylesterase activities were significantly lower in TLE and mesial temporal sclerosis(MTS)with and without psychiatric comorbidities than those in normal controls.The areas under the receiver operating characteristic curve of CMPAase were 0.893(0.037)for TLE and 0.895(±0.037)for MTS.Partial least squares path analysis showed that there were specific indirect effects of PON1 genotype on TLE severity(P<0.0001)and psychopathology(P<0.0001),which were both mediated by lowered CMPAase activity,while arylesterase activity was not significant.The severity of TLE was significantly associated with psychopathology scores.Furthermore,PON1 CMPAase activity was inversely associated with Mini Mental State Examination score.CONCLUSION The severity of TLE and comorbidities are to a large extent explained by reduced PON1 enzyme activities and by effects of the Q192R genotype,which are mediated by reduced CMPAase activity.Total PON1 status plays a key role in the pathophysiology of TLE,MTS and psychiatric comorbidities by increasing the risk of oxidative toxicity.PON1 enzyme activities are new drug targets in TLE to treat seizure frequency and psychiatric comorbidities.

Region Specific Effects of Maternal Immune Activation on Offspring Neuroimmune Function

Growing evidence suggests that maternal immune activation has a significant impact on the immuno-competence of the offspring. The present study aimed to characterize region-specific effects of maternal immune activation on the offspring’s neuroimmune function. The offspring born to dams treated with saline or lipopolysaccharide (LPS) at gestational day 18 was stimulated with saline or LPS at postnatal day 21, and the mRNA expression of various inflammatory genes in different brain regions of the offspring was analyzed. The offspring born to saline-treated dams exhibited a typical neuroimmune response with elevated levels of cytokines and chemokines following LPS stimulation in all four brain regions examined. In contrast, the offspring born to LPS- treated dams exhibited significantly reduced mRNA induction of cytokines and chemokines following LPS stimulation in the prefrontal cortex but not in the brainstem when compared with pups born to saline-treated dams. Furthermore, the mRNA expression of LPS-induced I-κBζ was significantly attenuated in the prefrontal cortex when compared with pups born to saline-treated dams. These results suggest that maternal LPS may have differential effects on the neuroimmune function in different regions of the offspring brain, and highlight the importance of maternal milieu in the development of neuroimmune function in the offspring.

Neuroimmune actions in the brain and interactions with the effects of alcohol

The neuroimmune system of the brain:Early studies(1990’s)on the neurological consequences of human immunodeficiency virus-1(HIV-1)infection in the brain were instrumental in establishing that specific brain cell types can function as an innate immune system within the brain and in that role influence cognitive function(Kaul et al.,2005).

Neuroimmune regulation in the pancreas

The pancreas exerts endocrine and exocrine functions in energy balance.The neural innervation and immune milieu are both crucial in supporting pancreatic homeostasis.The neuronal network connects the pancreas with the central nervous system(CNS)and the enteric nervous system(ENS)and sustains metabolic activities.The nerves in the pancreas are categorized as spinal sensory afferent fibers,vagal sensory afferent nerves,autonomic fibers of both sympathetic and parasympathetic divisions,and fibers from the ENS and intrapancreatic ganglia.They innervate different regions and various cell types,which collectively determine physiological functions.Studies have established that the diverse pathological conditions,including pancreatitis,diabetes,and pancreatic tumor,are attributed to aberrant immune reactions;however,it is largely not clear how the neuronal network may influence the disease conditions.Enlightened by the recent advances illuminating the organ-wide neuronal architecture and the dysfunctions in pancreatic disorders,this review will highlight emerging opportunities to explore the cellular interrelationship,particularly the neuroimmune components in pancreatic health and diseases.

Skin neuropathy and immunomodulation in diseases

Skin is a vital barrier tissue of the body.Immune responses in the skin must be precisely controlled,which would otherwise cause severe disease conditions such as psoriasis,atopic dermatitis,or pathogenic infection.Research evidence has increasingly demonstrated the essential roles of neural innervations,i.e.,sensory and sympathetic signals,in modulating skin immunity.Notably,neuropathic changes of such neural structures have been observed in skin disease conditions,implicating their direct involvement in various pathological processes.An in-depth understanding of the mechanism underlying skin neuropathy and its immunomodulatory effects could help reveal novel entry points for therapeutic interventions.Here,we summarize the neuroimmune interactions between neuropathic events and skin immunity,highlighting the current knowledge and future perspectives of this emerging research frontier.

Frontiers and future perspectives of neuroimmunology

Neuroimmunology is an interdisciplinary branch of biomedical science that emerges from the intersection of studies on the nervous system and the immune system.The complex interplay between the two systems has long been recognized.Research efforts directed at the underlying functional interface and associated pathophysiology,however,have garnered attention only in recent decades.In this narrative review,we highlight significant advances in research on neuroimmune interplay and modulation.A particular focus is on early-and middle-career neuroimmunologists in China and their achievements in frontier areas of"neuroimmune interface","neuro-endocrine-immune network and modulation","neuroimmune interactions in diseases","meningeal lymphatic and glymphatic systems in health and disease",and"tools and methodologies in neuroimmunology research".Key scientific questions and future directions for potential breakthroughs in neuroimmunology research are proposed.

Neuroimmune interactions and their roles in neurodegenerative diseases

The nervous system possesses bidirectional,sophisticated and delicate communications with the immune system.These neuroimmune interactions play a vitally important role in the initiation and development of many disorders,especially neurodegenerative diseases.Although scientific advancements have made tremendous progress in this field during the last few years,neuroimmune communications are still far from being elucidated.By organizing recent research,in this review,we discuss the local and intersystem neuroimmune interactions and their roles in Alzheimer’s disease,Parkinson’s disease and amyotrophic lateral sclerosis.Unveiling these will help us gain a better understanding of the process of interplay inside the body and how the organism maintains homeostasis.It will also facilitate a view of the diseases from a holistic,pluralistic and interconnected perspective,thus providing a basis of developing novel and effective methods to diagnose,intervene and treat diseases.

The role of cellular and molecular neuroimmune crosstalk in gut immunity

The gastrointestinal tract is densely innervated by the peripheral nervous system and populated by the immune system.These two systems critically coordinate the sensations of and adaptations to dietary,microbial,and damaging stimuli from the external and internal microenvironment during tissue homeostasis and inflammation.The brain receives and integrates ascending sensory signals from the gut and transduces descending signals back to the gut via autonomic neurons.Neurons regulate intestinal immune responses through the action of local axon reflexes or through neuronal circuits via the gut-brain axis.This neuroimmune crosstalk is critical for gut homeostatic maintenance and disease resolution.In this review,we discuss the roles of distinct types of gut-innervating neurons in the modulation of intestinal mucosal immunity.We will focus on the molecular mechanisms governing how different immune cells respond to neural signals in host defense and inflammation.We also discuss the therapeutic potential of strategies targeting neuroimmune crosstalk for intestinal diseases.

Mental Stress Affects the Occurrence and Development of Psoriasis Through Neuroendocrine-Immune Regulation:A Narrative Review

Psoriasis is a systemic immune-mediated inflammatory disease that presents at any age and is characterized by excessive proliferation and abnormal differentiation of keratinocytes as well as infiltration of multiple inflammatory cells.It has been gradually attracting more attention because of not only the increased risk of cardiovascular,metabolic,and autoimmune-related diseases but also the accompanying depression,anxiety,self-affirmation impairments,dementia,sleep disorders,and other mental disorders that place a substantial psychosocial burden on society and individuals.Mental and psychological disorders are involved in the occurrence,development,outcome,recurrence,and treatment of psoriasis through the neuroendocrine-immune signaling network.This review summarizes the pathogenesis of psychological and psychological disorders in patients with psoriasis with the aim of deepening clinicians’awareness of the mental and psychiatric comorbidities in patients with psoriasis.

The Levels of Plasma IL-1β,IL-6 of C57BL/6J Mice Treated with MPTP and Brain Lateralization

The work is to explore the relationship between the levels of cytokines(IL-1β and IL-6)in C57BL/6J mice treated with MPTP and brain lateralization.By using paw preference test,right-pawed,left-pawed mice models were established.Following single injection of 1-methyl-4-phenyl-2,3,6-tetrahydropyrid(MPTP)(40 mg/kg)to impair dopaminergic neuron,enzyme linked immunosorbent assay(ELISA)kits were used for detection of plasma levels of cytokines.The results showed that in saline treated C57BL/6J mice(control),there was no obvious difference observed between left-pawed and right-pawed mice in plasma levels of IL-1β and IL-6.In MPTP treated mice,there was no difference between level of IL-1β in left-pawed mice and that in right-pawed ones in statistics,that is,they were increased on day 1 and day 3,but decreased on day 6.The plasma level of IL-6 was lower in left-pawed than that in right-pawed mice (p<0.005)after MPTP treatment. On day 1 and day 3,the level of IL-6 was almost the same as control;on day 6,it was significantly increased, higher than that of control(p<0.001)in left-pawed mice.While in right-pawed mice,on day 1 and day 3,it was no different from control,too.And on day 6,it significantly increased in compared with control(p<0.005).In conclusion,the level of plasma IL-6 of C57BL/6J mice treated with MPTP increased.The variation of IL-6 was correlated to brain lateralization.Cellular & Molecular Immunology.2004;1(3):219-223.

LFA-1 antagonist (BIRT377) similarly reverses peripheral neuropathic pain in male and female mice with underlying sex divergent peripheral immune proinflammatory phenotypes

Aim:The majority of preclinical studies investigating aberrant glial-neuroimmune actions underlying neuropathic pain have focused on male rodent models.Recently,studies have shown peripheral immune cells play a more prominent role than glial cells in mediating pathological pain in females.Here,we compared the onset and duration of allodynia in males and females,and the anti-allodynic action of a potentially novel therapeutic drug(BIRT377)that not only antagonizes the action of lymphocyte function-associated antigen-1(LFA-1)to reduce cell migration in the periphery,but may also directly alter the cellular inflammatory bias.Methods:Male and female mice were subjected to peripheral nerve injury chronic constriction injury(CCI)applying two methods,using either 4-0 or 5-0 chromic gut suture material,to examine potential sex differences in the onset,magnitude and duration of allodynia.Hindpaw sensitivity before and after CCI and application of intravenous BIRT377 was assessed.Peripheral and spinal tissues were analyzed for protein(multiplex electrochemiluminescence technology)and mRNA expression(quantitative real-time PCR).The phenotype of peripheral T cells was determined using flow cytometry.Results:Sex differences in proinflammatory CCL2 and IL-1βand the anti-inflammatory IL-10 were observed from a set of cytokines analyzed.A profound proinflammatory T cell(Th17)response in the periphery and spinal cord was also observed in neuropathic females.BIRT377 reversed pain,reduced IL-1βand TNF,and increased IL-10 and transforming growth factor(TGF)-β1,also an anti-inflammatory cytokine,in both sexes.However,female-derived T cell cytokines are transcriptionally regulated by BIRT377,as demonstrated by reducing proinflammatory IL-17A production with concurrent increases in IL-10,TGF-β1 and the anti-inflammatory regulatory T cell-related factor,FOXP3.Conclusion:This study supports that divergent peripheral immune and neuroimmune responses during neuropathy exists between males and females.Moreover,the modulatory actions of BIRT377 on T cells during neuropathy are predominantly specific to females.These data highlight the necessity of including both sexes for studying drug efficacy and mechanisms of action in preclinical studies and clinical trials.