Animals ; Caffeine/adverse effects* ; Central Nervous System Stimulants/adverse effects* ; Dose-Response Relationship, Drug ; Female ; Fetal Growth Retardation/chemically induced* ; Immune System Diseases/chemically induced* ; Male ; Organ Size/drug effects* ; Pregnancy ; Pregnancy Complications/immunology* ; Rats ; Spleen/growth & development*

Objective: Due to the special anatomical structure and pathophysiological mechanism of the central nervous system (CNS), there is a big difference between the repair of brain injury and other systems of the body. More and more evidence shows that targetedly reducing the autoimmune response of brain tissue without affecting the immune function in other parts of the body will be the best optimized treatment for brain injury. Data Sources: This review was based on data in articles published in PubMed up to June 5, 2017, with the following keywords: "immune tolerance", "traumatic brain injury", and "central nervous system". Study Selection: Original articles and critical reviews on immune tolerance and brain damage were selected for this review. References of the retrieved articles were also screened to search for potentially relevant papers. Results: The CNS is isolated from the immune system through the blood-brain barrier. After brain injury, brain antigens are released into the systemic circulation to induce damaging immune responses. Immune tolerance can effectively reduce the brain edema and neurological inflammatory response after brain injury, which is beneficial to the recovery of neurological function. The clinical application prospect and theoretical research value of the treatment of immune tolerance on traumatic brain injury (TBI) is worth attention. Conclusions The establishment of immune tolerance mechanism has a high clinical value in the treatment of TBI. It opens up new opportunities for the treatment of brain damage.
Brain ; immunology ; Brain Injuries, Traumatic ; immunology ; therapy ; Central Nervous System ; Humans ; Immune Tolerance ; Immunotherapy

BACKGROUNDTh9 cells are a newly discovered CD4+ T helper cell subtype, characterized by high interleukin (IL)-9 secretion. Growing evidences suggest that Th9 cells are involved in the pathogenic mechanism of multiple sclerosis (MS). Mast cells are multifunctional innate immune cells, which are perhaps best known for their role as dominant effector cells in allergies and asthma. Several lines of evidence point to an important role for mast cells in MS and its animal models. Simultaneously, there is dynamic "cross-talk" between Th9 and mast cells. The aim of the present study was to examine the IL-9-mast cell axis in experimental autoimmune encephalomyelitis (EAE) and determine its interaction after neutralizing anti-IL-9 antibody treatment.

METHODSFemale C57BL/6 mice were randomly divided into three groups (n = 5 in each group): mice with myelin oligodendrocyte glycoprotein (MOG)-induced EAE (EAE group), EAE mice treated with anti-IL-9 antibody (anti-IL-9 Abs group), and EAE mice treated with IgG isotype control (IgG group). EAE clinical score was evaluated. Mast cells from central nervous system (CNS) were detected by flow cytometry. The production of chemokine recruiting mast cells in the CNS was explored by reverse transcription-polymerase chain reaction (RT-PCR). In mice with MOG-induced EAE, the expression of IL-9 receptor (IL-9R) complexes in CNS and spleen mast cells was also explored by RT-PCR, and then was repeating validated by immunocytochemistry. In vitro, spleen cells from EAE mice were cultured with anti-IL-9 antibody, and quantity of mast cells was counted by flow cytometry after co-culture.

RESULTSCompared with IgG group, IL-9 blockade delayed clinical disease onset and ameliorated EAE severity (t = -2.217, P = 0.031), accompany with mast cells infiltration decreases (day 5: t = -8.005, P < 0.001; day 15: t = -11.857, P < 0.001; day 20: t = -5.243, P = 0.001) in anti-IL-9 Abs group. The messenger RNA expressions of C-C motif chemokine ligand 5 (t = -5.932, P = 0.003) and vascular cell adhesion molecule-1 (t = -4.029, P = 0.004) were significantly decreased after IL-9 neutralization in anti-IL-9 Abs group, compared with IgG group. In MOG-induced EAE, the IL-9R complexes were expressed in CNS and spleen mast cells. In vitro, splenocytes cultured with anti-IL-9 antibody showed significantly lower levels of mast cells in a dose-dependent manner, compared with splenocytes cultured with anti-mouse IgG (5 μg/ml: t = -0.894, P = 0.397; 10 μg/ml: t = -3.348, P = 0.019; 20 μg/ml: t = -7.639, P < 0.001).

CONCLUSIONSThis study revealed that IL-9 neutralization reduced mast cell infiltration in CNS and ameliorated EAE, which might be relate to the interaction between IL-9 and mast cells.

Animals ; Antibodies ; therapeutic use ; Central Nervous System ; metabolism ; Encephalomyelitis, Autoimmune, Experimental ; drug therapy ; metabolism ; Female ; Immunohistochemistry ; Interleukin-9 ; antagonists & inhibitors ; immunology ; metabolism ; Mast Cells ; metabolism ; Mice ; Mice, Inbred C57BL ; RNA, Messenger ; genetics ; Reverse Transcriptase Polymerase Chain Reaction

BACKGROUNDConventional magnetic resonance imaging (MRI) is the preferred neuroimaging method in the evaluation of neuropsychiatric systemic lupus erythematosus (NPSLE). The purpose of this study was to investigate the association between clinical and immunological features with MRI abnormalities in female patients with NPSLE, to screen for the value of conventional MRI in NPSLE.

METHODSA total of 59 female NPSLE patients with conventional MRI examinations were enrolled in this retrospective study. All patients were classified into different groups according to MRI abnormalities. Both clinical and immunological features were compared between MRI abnormal and normal groups. One-way analysis of variance was used to compare the systemic lupus erythematosus disease activity index (SLEDAI) score for MRI abnormalities. Multivariate logistic regression analysis investigated the correlation between immunological features, neuropsychiatric manifestations, and MRI abnormalities.

RESULTSThirty-six NPSLE patients (61%) showed a variety of MRI abnormalities. There were statistically significant differences in SLEDAI scores (P < 0.001), incidence of neurologic disorders (P = 0.001), levels of 24-h proteinuria (P = 0.001) and immunoglobulin M (P = 0.004), and incidence of acute confusional state (P = 0.002), cerebrovascular disease (P = 0.004), and seizure disorder (P = 0.028) between MRI abnormal and normal groups. In the MRI abnormal group, SLEDAI scores for cerebral atrophy (CA), cortex involvement, and restricted diffusion (RD) were much higher than in the MRI normal group (P < 0.001, P = 0.002, P = 0.038, respectively). Statistically significant positive correlations between seizure disorder and cortex involvement (odds ratio [OR] = 14.90; 95% confidence interval [CI], 1.50-151.70; P = 0.023) and cerebrovascular disease and infratentorial involvement (OR = 10.00; 95% CI, 1.70-60.00; P = 0.012) were found.

CONCLUSIONSMRI abnormalities in NPSLE, especially CA, cortex involvement, and RD might be markers of high systemic lupus erythematosus activity. Some MRI abnormalities might correspond to neuropsychiatric manifestations and might be helpful in understanding the pathophysiology of NPSLE.

Adolescent ; Adult ; Child ; Child, Preschool ; Female ; Humans ; Lupus Erythematosus, Systemic ; immunology ; pathology ; Lupus Vasculitis, Central Nervous System ; immunology ; pathology ; Magnetic Resonance Imaging ; Middle Aged ; Retrospective Studies

With extended life of HIV-infected patients due to highly active anti-retroviral therapy (HAART), the rate of HIV associated neurocognitive disorder (HAND) remains high and attracts much attention. The evidence is clear that cytokines are elevated in the blood of patients with HIV infection, which contribute to elevating the permeability of blood-brain barrier. Benefiting from that, cells in the brain are infected with HIV that has accelerated through the blood-brain barrier both as cell-free virus and infected immune cells including monocytes and T cells. Upon migration into the central nervous system, HIV-infected monocytes and T cells not only infect brain resident cells but also produce proinflammatory cytokines such as TNF and IL-1ß, which further activate microglia and astrocytes. These activated brain glial cells and perivascular macrophages, which release inflammatory mediators, are the main contributors to neuroinflammation resulting in neuronal dysfunction. The pathogenesis of HAND is multifaceted, however, mounting evidence indicates that HIV related neuroinflammation plays a major role, which should be the focus of therapeutic research for HAND in future.
Astrocytes ; Blood-Brain Barrier ; Brain ; Cell Movement ; Central Nervous System ; Cytokines ; HIV Infections ; immunology ; HIV-1 ; Humans ; Macrophages ; Microglia ; Monocytes ; Neurocognitive Disorders ; immunology ; Neurons ; T-Lymphocytes

The immune hypothesis of major depressive disorder (MDD) fits well with the supposed interaction between genetic and environmental factors in disorders with a complicated etiopathogenesis. It has been suggested that infectious diseases are associated with MDD in that cytokines may play a critical role as a key modulator in the transition between infection and the development of MDD. It has been also suggested that antidepressants have immunomodulatory effects on some cytokines and cytokine receptors, although the exact mechanism has not yet been fully elucidated. Among cytokines, monocyte chemoattractant protein-1 (MCP-1) is especially well known and has attracted considerable interest owing to its immunomodulatory functions. MCP-1 is expressed in highly regionalized neuronal areas in the brain, leading to kind of modulation of neuronal activity and neuroendocrine functions commonly seen in patients with MDD. Additionally, it is involved in the control of other cytokines that have been consistently proposed as associated with the development of MDD. It also has a possible role in the neurodegenerative process of a number of central nervous system (CNS) diseases. Hence, this paper draws from the perspective of immunology to offer several suggestions about the role of MPC-1 in the development of MDD.
Allergy and Immunology ; Antidepressive Agents ; Brain ; Central Nervous System ; Chemokine CCL2* ; Communicable Diseases ; Cytokines ; Depression ; Depressive Disorder, Major* ; Humans ; Neurons ; Receptors, Cytokine

The immune hypothesis of major depressive disorder (MDD) fits well with the supposed interaction between genetic and environmental factors in disorders with a complicated etiopathogenesis. It has been suggested that infectious diseases are associated with MDD in that cytokines may play a critical role as a key modulator in the transition between infection and the development of MDD. It has been also suggested that antidepressants have immunomodulatory effects on some cytokines and cytokine receptors, although the exact mechanism has not yet been fully elucidated. Among cytokines, monocyte chemoattractant protein-1 (MCP-1) is especially well known and has attracted considerable interest owing to its immunomodulatory functions. MCP-1 is expressed in highly regionalized neuronal areas in the brain, leading to kind of modulation of neuronal activity and neuroendocrine functions commonly seen in patients with MDD. Additionally, it is involved in the control of other cytokines that have been consistently proposed as associated with the development of MDD. It also has a possible role in the neurodegenerative process of a number of central nervous system (CNS) diseases. Hence, this paper draws from the perspective of immunology to offer several suggestions about the role of MPC-1 in the development of MDD.
Allergy and Immunology ; Antidepressive Agents ; Brain ; Central Nervous System ; Chemokine CCL2* ; Communicable Diseases ; Cytokines ; Depression ; Depressive Disorder, Major* ; Humans ; Neurons ; Receptors, Cytokine

Neurognathostomiasis is a severe form of human gnathostomiasis which can lead to disease and death. Diagnosis of neurognathostomiasis is made presumptively by using clinical manifestations. Immunoblotting, which recognizes antigenic components of molecular mass 21 kDa and 24 kDa in larval extracts of Gnathostoma spinigerum (Gs 21/24), has high sensitivity and specificity for diagnosis of neurognathostomiasis. However, only very small amounts of the Gs 21/24 antigens can be prepared from parasites harvested from natural or experimental animals. To overcome this problem, we recently produced a recombinant matrix metalloproteinase (rMMP) protein from G. spinigerum. In this study, we evaluated this rMMP alongside the Gs 21/24 antigens for serodiagnosis of human neurognathostomiasis. We studied sera from 40 patients from Srinagarind Hospital, Khon Kaen University, Thailand, with clinical criteria consistent with those of neurognathostomiasis, and sera from 30 healthy control adults from Thailand. All sera were tested for specific IgG antibodies against both G. spinigerum crude larval extract and rMMP protein using immunoblot analysis. The sensitivity and specificity for both antigenic preparations were all 100%. These results show that G. spinigerum rMMP protein can be used as an alternative diagnostic antigen, in place of larval extract, for serodiagnosis of neurognathostomiasis.
Adult ; Animals ; Antibodies, Helminth/blood ; Antigens, Helminth/*diagnostic use/genetics/isolation & purification ; Central Nervous System Parasitic Infections/*diagnosis/parasitology ; Gnathostoma/enzymology/immunology/*isolation & purification ; Gnathostomiasis/*diagnosis/parasitology ; Healthy Volunteers ; Humans ; Immunoblotting/methods ; Immunoglobulin G/blood ; Matrix Metalloproteinases/*diagnostic use/genetics/isolation & purification ; Parasitology/*methods ; Prospective Studies ; Recombinant Proteins/diagnostic use/genetics/isolation & purification ; Sensitivity and Specificity ; Serologic Tests/methods ; Thailand

Microglia, the resident immune effective cells of the central nervous system, play crucial roles in mediating immune-related process. It becomes activated quickly in response to even minor pathological insults and participates in series of immune responses. Under physiological conditions, most microglia stay in a typical resting state, with ramified processes continuously extending and retracting from surrounding neural tissues, suggesting an important function of resting microglia. Recent studies indicate that resting microglia can regulate many physiological processes, including neural development, neural circuit formation, neuronal activity and plasticity, and animal grooming behavior. Here, we review the properties of resting microglia and further discuss how microglia participate in the above-mentioned functional regulation under physiological conditions.
Animals ; Central Nervous System ; cytology ; Humans ; Microglia ; immunology ; physiology

INTRODUCTIONNeuropsychiatric manifestations can occur in up to two-thirds of patients with systemic lupus erythematosus (SLE). The presentations as well as the underlying immunopathogenic mechanisms can be heterogeneous and therefore have an enormous impact on therapeutic options.

CLINICAL PICTUREWe describe 2 patients who presented similarly with acute onset binocular reversible visual loss. The first patient had anti-phospholipid syndrome and optic neuritis, while the second patient suffered from posterior reversible leukoencephalopathy syndrome.

TREATMENTPatient one was treated with anti-coagulation and immunosuppression while the second patient required the withdrawal of immunosuppression and supportive therapy.

OUTCOMEBoth patients responded favourably and had complete visual recovery.

CONCLUSIONSDifferent management strategies have to be employed for similar presentations having different aetiologies, underscoring the need for constant clinical vigilance.

Adult ; Antiphospholipid Syndrome ; complications ; etiology ; Brain Diseases ; etiology ; immunology ; Epilepsy, Tonic-Clonic ; etiology ; Female ; Humans ; Lupus Erythematosus, Systemic ; complications ; microbiology ; physiopathology ; therapy ; Lupus Vasculitis, Central Nervous System ; diagnosis ; Magnetic Resonance Imaging ; Optic Neuritis ; etiology ; Salmonella Infections ; complications ; Salmonella enteritidis ; Time Factors ; Vision Disorders ; etiology ; immunology