Brain regions involved in modulation of immune responses

Abstract Background. West Nile virus (WNV) infection in humans can result in severe, acute encephalitis typically involving subcortical gray matter brain regions. West Nile virus replication within specific human brain regions from a human case of acute encephalitis has not been studied. Methods. We describe a fatal case of WNV encephalitis in which we obtained tissue from specific brain regions at autopsy to evaluate viral-host interactions using next-generation sequencing and immunohistochemistry analysis. Results. We found that WNV populations in the injured subcortical brain regions exhibited increased amino acid variation and increased expression of specific interferon genes compared with cortical tissues despite similar viral burden. Conclusions. These observational, patient-based data suggest that neuronal injury and the strength of viral selection pressure may be associated with the level of the innate immune responses. Further studies in human and animal models evaluating the role of innate immune responses on injury patterns and viral selection pressure are needed.

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Intrastriatal injection of preformed alpha-synuclein fibrils alters central and peripheral immune cell profiles in non-transgenic mice

Journal of Neuroinflammation ◽

10.1186/s12974-019-1636-8 ◽

2019 ◽

Vol 16 (1) ◽

Cited By ~ 9

Author(s):

Rachael H. Earls ◽

Kelly B. Menees ◽

Jaegwon Chung ◽

James Barber ◽

Claire-Anne Gutekunst ◽

...

Keyword(s):

Immune Responses ◽

Immune Cell ◽

Lewy Bodies ◽

Brain Regions ◽

Alpha Synuclein ◽

Molecular Pattern ◽

Immune Phenotypes ◽

Spleen And Lymph Nodes ◽

The Brain ◽

Intrastriatal Injection

AbstractParkinson’s disease (PD) is characterized by the accumulation of alpha-synuclein (α-syn) inclusions, the major component of Lewy bodies. Extracellular α-syn aggregates act as a damage-associated molecular pattern (DAMP) and the presence of autoantibodies against α-syn species in the cerebrospinal fluid and the serum of PD patients implicate the involvement of innate and adaptive immune responses. In non-transgenic (Tg) mice, intrastriatal injection of preformed fibril (PFF) α-syn results in widespread pathologic α-syn inclusions in the CNS. While the PFF model has been broadly utilized to study the mechanistic relationship between α-syn transmission and other neuropathological phenotypes, the immune phenotypes in this model are not clearly demonstrated. This study aimed to characterize the immune phenotypes during pathologic α-syn propagation by utilizing PFF α-syn–injected non-tg mice. Here, we showed that pathologic α-syn inclusions are prevalent in various brain regions and the gut at 5 months post injection (p.i.), preceding the degeneration of dopaminergic neurons in substantia nigra (SN). We discovered a distinct inflammatory response involving both activation of microglia and astrocytes and infiltration of B, CD4+ T, CD8+ T, and natural killer cells in the brain at 5 months p.i. Moreover, PFF α-syn–injected mice display significant alterations in the frequency and number of leukocyte subsets in the spleen and lymph nodes with minimum alterations in the blood. Our data provide primary evidence that intracerebral-initiated synucleinopathies in non-tg mice alter immune cell profiles both in the CNS and peripheral lymphoid organs. Furthermore, our data provides support for utilizing this mouse model to assess the mechanistic connection between immune responses and synuclein pathology.

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Co-Therapy of Albendazole and Dexamethasone Reduces Pathological Changes in the Cerebral Parenchyma of Th-1 and Th-2 Dominant Mice Heavily Infected with Angiostrongylus cantonensis: Histopathological and RNA-seq Analyses

Biomolecules ◽

10.3390/biom11040536 ◽

2021 ◽

Vol 11 (4) ◽

pp. 536

Author(s):

Kai-Yuan Jhan ◽

Chien-Ju Cheng ◽

Shih-Ming Jung ◽

Yi-Jen Lai ◽

Kuang-Yao Chen ◽

...

Keyword(s):

Immune Responses ◽

Brain Regions ◽

Angiostrongylus Cantonensis ◽

Rna Seq ◽

Pathological Changes ◽

Histopathological Findings ◽

Third Stage ◽

Cerebral Parenchyma ◽

Hematoxylin And Eosin ◽

Th 1

Administration of albendazole alone was not very suitable for the treatment of cerebral angiostrongyliasis. This study was designed to evaluate the effects of the co-therapy of this drug and dexamethasone in Th-1 and Th-2 dominant mice infected with Angiostrongylus cantonensis. Each of BALB/c and C57BL/6 mice infected with 50 A. cantonensis third-stage larvae were administered albendazole (10 mg/kg/day) alone, dexamethasone (0.5 mg/kg/day) alone, or co-therapy of the two drugs from day 7 or 14 post-infection for 7 or 14 days. After sacrifice, coronal slices were prepared from five brain regions and stained with hematoxylin and eosin. Eight pathological changes were employed to determine the therapeutic effectiveness using a scoring system. RNA-seq analysis was performed to confirm the histopathological findings. The infected BALB/c and C57BL/6 mice had similar patterns in the pathological changes. Meningitis, hemorrhage, size of worms, and encephalitis in the cerebral parenchyma were slighter in the mice treated with co-therapy than the remaining groups. Mice treated from day 14 had more severe changes than those from day 7. The histopathological findings were found to be consistent to immune responses determined by RNA-seq analysis. Co-therapy was determined to reduce pathological changes after administration to mice infected with A. cantonensis.

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Abstract P156: Fiber-rich Diet Suppresses Lactobacillus And Increases Blood Pressure In The Shr Independently Of T-lymphocyte Immune Responses

Hypertension ◽

10.1161/hyp.68.suppl_1.p156 ◽

2016 ◽

Vol 68 (suppl_1) ◽

Author(s):

Tao Yang ◽

Luis M Colon-Perez ◽

Kacy L Magee ◽

Wendi L Malphurs ◽

Thomas W Vickroy ◽

...

Keyword(s):

Blood Pressure ◽

Immune Responses ◽

T Lymphocyte ◽

Neural Activity ◽

Control Diet ◽

Brain Regions ◽

Neural Activation ◽

Spontaneously Hypertensive ◽

The Impact ◽

Diet Switch

Introduction: Gut dysbiosis has been linked to hypertension in both rodents and humans. Microbial metabolites such as propionate have been shown to regulate blood pressure (BP), while butyrate, one of the major fermented end-products of fiber, reportedly produces beneficial anti-inflammatory effects in multiple dysbiosis-related diseases. Therefore, we tested the impact of a fiber-rich, butyrolytic diet on BP regulation and immune responses in the spontaneously hypertensive rats (SHR). Methods: SHR (5 wo) were placed on either the fructooligosaccharides/inulin-rich diet (Fiber, N=6), or its calorie-matched control diet (Control, N=6) (Research Diets, Inc.) for 10 weeks. Baseline BP was measured by tail cuff every week for the duration of the study. Fecal samples were collected for HPLC analysis of butyrate, and Lactobacillus population by QPCR. Manganese-enhanced magnetic resonance imaging was used to monitor neural activity in cardioregulatory brain regions. Blood was analyzed for circulating lymphocyte populations previously implicated in BP control in the SHR (CD3 + CD45 + , CD4 + CD25 + , CD8 + ). Results: Fiber-rich diet produced an increase in fecal butyrate levels as early as five weeks (Control vs. Fiber, 4.9umol/g vs. 9.7umol/g, p=0.068, N=6). This was associated with contraction of fecal Lactobacillus (47.5% vs. 5.9%, p=0.0008, N=6). However, we observed significantly higher systolic BP (181.4mmHg vs. 201.7 mmHg, p=0.0088, N=6) in the fiber group compared with control, beginning with week 9 post-diet switch. Changes in neural activation were observed in the paraventricular nucleus of hypothalamus (PVN) (3.3 voxel vs. 7.3 voxel, p=0.26) and amygdala (93.3 voxel vs. 31 voxel, p=0.0059, N=3). No changes in circulating T-lymphocytes were observed between the two groups: CD3 + CD45 + (32.4% vs. 32.1% lymphocytes); CD4 + CD25 + (1.05% vs. 0.78% lymphocytes); CD8 + (18.7% vs. 16.2% lymphocytes, N=6) at week 10 post-diet switch. Conclusion: Fiber-rich diet suppression of Gut Lactobacillus is associated with increase in BP in the SHR, independently of T-lymphocyte responses. The observed higher neural activity in PVN and lower in amygdala in the fiber group suggest direct effects of gut bacterial metabolites on brain cardioregulatory regions.

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Acute peripheral immune activation alters cytokine expression and glial activation in the early postnatal rat brain

Journal of Neuroinflammation ◽

10.1186/s12974-019-1569-2 ◽

2019 ◽

Vol 16 (1) ◽

Cited By ~ 4

Author(s):

Matthew Bruce ◽

Karin M. Streifel ◽

Casey A. Boosalis ◽

Luke Heuer ◽

Eduardo A. González ◽

...

Keyword(s):

Immune Responses ◽

Mixed Model ◽

Brain Slices ◽

Brain Regions ◽

Brown Norway ◽

Dependent Manner ◽

Immune Challenge ◽

Sample Collection ◽

Post Challenge ◽

The Brain

Abstract Background Neuroinflammation can modulate brain development; however, the influence of an acute peripheral immune challenge on neuroinflammatory responses in the early postnatal brain is not well characterized. To address this gap in knowledge, we evaluated the peripheral and central nervous system (CNS) immune responses to a mixed immune challenge in early postnatal rats of varying strains and sex. Methods On postnatal day 10 (P10), male and female Lewis and Brown Norway rats were injected intramuscularly with either a mix of bacterial and viral components in adjuvant, adjuvant-only, or saline. Immune responses were evaluated at 2 and 5 days post-challenge. Cytokine and chemokine levels were evaluated in serum and in multiple brain regions using a Luminex multiplex assay. Multi-factor ANOVAs were used to compare analyte levels across treatment groups within strain, sex, and day of sample collection. Numbers and activation status of astrocytes and microglia were also analyzed in the cortex and hippocampus by quantifying immunoreactivity for GFAP, IBA-1, and CD68 in fixed brain slices. Immunohistochemical data were analyzed using a mixed-model regression analysis. Results Acute peripheral immune challenge differentially altered cytokine and chemokine levels in the serum versus the brain. Within the brain, the cytokine and chemokine response varied between strains, sexes, and days post-challenge. Main findings included differences in T helper (Th) type cytokine responses in various brain regions, particularly the cortex, with respect to IL-4, IL-10, and IL-17 levels. Additionally, peripheral immune challenge altered GFAP and IBA-1 immunoreactivity in the brain in a strain- and sex-dependent manner. Conclusions These findings indicate that genetic background and sex influence the CNS response to an acute peripheral immune challenge during early postnatal development. Additionally, these data reinforce that the developmental time point during which the challenge occurs has a distinct effect on the activation of CNS-resident cells.

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Neurological Mechanisms in Immune Regulation

10.36811/ijbm.2019.110011 ◽

2019 ◽

pp. 88-92

Author(s):

Rodgers W ◽

Tucker HO

Keyword(s):

Nervous System ◽

Immune Responses ◽

Immune Function ◽

Inflammatory Responses ◽

Brain Regions ◽

The Body ◽

Active Inference ◽

Peripheral Immune System ◽

The Central Nervous System ◽

The Brain

This paper is a survey of the neurological mechanisms involved in the regulation of immune function. Its specific focus is to explore the anatomical regions of the brain that mediate inflammatory responses throughout the body. It begins by briefly reviewing experiments that elucidate a connection between psychological process and immune function. It also introduces the physiological connections that enable communication between the central nervous system and peripheral immune system. It then examines the brain regions involved in regulating immune responses, with additional insights drawn from the principles of active inference in interoceptive processes. Keywords: Psychoneuroimmunology; Inflammation; Autonomic nervous system; conditioning; Insula; interoception; Active inference; Bayesian

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Synaptic organization of the gustatory NST

Proceedings, annual meeting, Electron Microscopy Society of America ◽

10.1017/s0424820100168487 ◽

1994 ◽

Vol 52 ◽

pp. 150-151

Author(s):

M. C. Whitehead

Keyword(s):

Central Nervous System ◽

Dendritic Spines ◽

Fundamental Problem ◽

Cell Types ◽

Brain Regions ◽

Excitatory Synapses ◽

Solitary Tract ◽

Synaptic Organization ◽

Synaptic Junctions ◽

Afferent Terminals

A fundamental problem in taste research is to determine how gustatory signals are processed and disseminated in the mammalian central nervous system. An important first step toward understanding information processing is the identification of cell types in the nucleus of the solitary tract (NST) and their synaptic relationships with oral primary afferent terminals. Facial and glossopharyngeal (LIX) terminals in the hamster were labelled with HRP, examined with EM, and characterized as containing moderate concentrations of medium-sized round vesicles, and engaging in asymmetrical synaptic junctions. Ultrastructurally the endings resemble excitatory synapses in other brain regions.Labelled facial afferent endings in the RC subdivision synapse almost exclusively with distal dendrites and dendritic spines of NST cells. Most synaptic relationships between the facial synapses and the dendrites are simple. However, 40% of facial endings engage in complex synaptic relationships within glomeruli containing unlabelled axon endings particularly ones termed "SP" endings. SP endings are densely packed with small, pleomorphic vesicles and synapse with both the facial endings and their postsynaptic dendrites by means of nearly symmetrical junctions.

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