The Relationship between the Neuroimmune System and Peripheral Responses

A special issue of Brain Sciences (ISSN 2076-3425). This special issue belongs to the section "Molecular and Cellular Neuroscience".

Deadline for manuscript submissions: closed (31 August 2018) | Viewed by 20248

Special Issue Editor

1. School of Population Health, University of Mississippi Medical Center, Jackson, MS 39216, USA
2. SOM-Obstetrics & Gynecology Department, University of Mississippi Medical Center, Jackson, MS 39216, USA
3. Department of Pharmacology & Toxicology, University of Mississippi Medical Center, Jackson, MS 39216, USA
Interests: uterine fibroids; mental health; HELLP syndrome; preeclampsia; hypertension
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Special Issue Information

Dear Colleagues,

Activation of the innate immune system in the brain can lead to changes in neuronal homeostasis, structural changes within the brain, and behavioural changes. How the innate immune system is regulated differs between pathological conditions and can be influenced by pharmaceutical and behavioural therapy. Furthermore, of the many long-term effects of innate immune system activation in temporary conditions, such as pregnancy, surgery, or situations of acute stress, drug addictions have not been fully elucidated.

While it is clear that there is a relationship between the brain and the immune system, the role that the immune system plays in a variety of pathological states is still unclear. Therefore, we are seeking manuscripts or review articles to help elucidate these and other relationships.

Dr. Kedra Wallace
Guest Editor

Manuscript Submission Information

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Keywords

  • Innate immune system
  • Neuroprotection
  • Pathophysiology
  • Substance abuse
  • Developmental Disorders
  • Neurodegeneration

Published Papers (4 papers)

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Research

13 pages, 2450 KiB  
Article
Differential Expression of Genes Related to Innate Immune Responses in Ex Vivo Spinal Cord and Cerebellar Slice Cultures Infected with West Nile Virus
Brain Sci. 2019, 9(1), 1; https://doi.org/10.3390/brainsci9010001 - 24 Dec 2018
Cited by 4 | Viewed by 4125
Abstract
West Nile virus (WNV) infection results in a spectrum of neurological symptoms, ranging from a benign fever to severe WNV neuroinvasive disease with high mortality. Many who recover from WNV neuroinvasive infection present with long-term deficits, including weakness, fatigue, and cognitive problems. While [...] Read more.
West Nile virus (WNV) infection results in a spectrum of neurological symptoms, ranging from a benign fever to severe WNV neuroinvasive disease with high mortality. Many who recover from WNV neuroinvasive infection present with long-term deficits, including weakness, fatigue, and cognitive problems. While neurons are a main target of WNV, other cell types, especially astrocytes, play an important role in promoting WNV-mediated central nervous system (CNS) damage. Conversely, it has been shown that cultured primary astrocytes secrete high levels of interferons (IFNs) immediately after WNV exposure to protect neighboring astrocytes, as well as neurons. However, how intrinsic responses to WNV in specific cell types and different regions of the brain modify immune protection is not fully understood. Here, we used a mouse ex vivo spinal cord slice culture (SCSC) and cerebellar slice culture (CSC) models to determine the innate immune responses specific to the CNS during WNV infection. Slices were prepared from the spinal cord and cerebellar tissue of 7–9-day-old mouse pups. Four-day-old SCSC or CSC were infected with 1 × 103 or 1 × 105 PFU of WNV, respectively. After 12 h exposure to WNV and 3 days post-infection in normal growth media, the pooled slice cultures were processed for total RNA extraction and for gene expression patterns using mouse Affymetrix arrays. The expression patterns of a number of genes were significantly altered between the mock- and WNV-treated groups, both in the CSCs and SCSCs. However, distinct differences were observed when CSC data were compared with SCSC. CSCs showed robust induction of interferons (IFNs), IFN-stimulated genes (ISGs), and regulatory factors. Some of the antiviral genes related to IFN were upregulated more than 25-fold in CSCs as compared to mock or SCSC. Though SCSCs had twice the number of dysregulated genes, as compared CSCs, they exhibited a much subdued IFN response. In addition, SCSCs showed astrogliosis and upregulation of astrocytic marker genes. In sum, our results suggest that early anti-inflammatory response to WNV infection in CSCs may be due to large population of distinct astrocytic cell types, and lack of those specialized astrocytes in SCSC may make spinal cord cells more susceptible to WNV damage. Further, the understanding of early intrinsic immune response events in WNV-infected ex vivo culture models could help develop potential therapies against WNV. Full article
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13 pages, 1145 KiB  
Article
Peripheral Anti-Angiogenic Imbalance during Pregnancy Impairs Myogenic Tone and Increases Cerebral Edema in a Rodent Model of HELLP Syndrome
Brain Sci. 2018, 8(12), 216; https://doi.org/10.3390/brainsci8120216 - 06 Dec 2018
Cited by 8 | Viewed by 5288
Abstract
Using an animal model of hemolysis elevated liver enzymes low platelets (HELLP) that has systemic inflammation and neuroinflammation we wanted to determine if blood brain barrier (BBB) permeability, cerebral edema, vascular tone, and occludin expression were altered in pregnant rats. Anti-angiogenic proteins sFlt-1 [...] Read more.
Using an animal model of hemolysis elevated liver enzymes low platelets (HELLP) that has systemic inflammation and neuroinflammation we wanted to determine if blood brain barrier (BBB) permeability, cerebral edema, vascular tone, and occludin expression were altered in pregnant rats. Anti-angiogenic proteins sFlt-1 and sEng (4.7 and 7 µg/kg/day, respectively) were chronically infused into normal pregnant (NP) rats beginning on gestational day 12 via a mini-osmotic pump. On gestational day 19, blood pressure was measured via a carotid catheter and brains were collected. BBB permeability was assessed in select brain regions from rats infused with 0.5 mg/mL Texas Red Dextran and phenylephrine. Occludin, sFlt-1, and sEng were analyzed via western blot or ELISA. Infusion of sFlt-1 and sEng into NP rats increased hemolysis and liver enzymes, and decreased platelets and led to hypertension. HELLP rats had significant impairment in the myogenic response and increased BBB permeability in the posterior cortex and brainstem. Brain water content in the posterior cortex was increased and sEng protein expression in the brainstem was significantly increased in HELLP rats. The results from this study suggest that a peripheral anti-angiogenic imbalance during pregnancy is associated with decreased myogenic tone, vasogenic edema, and an increase in BBB permeability, but not anti-angiogenic imbalance in the brain. Full article
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16 pages, 3368 KiB  
Article
Lipopolysaccharide Challenge Reveals Hypothalamic-Pituitary-Adrenal Axis Dysfunction in Murine Systemic Lupus Erythematosus
Brain Sci. 2018, 8(10), 184; https://doi.org/10.3390/brainsci8100184 - 04 Oct 2018
Cited by 7 | Viewed by 4405
Abstract
Crosstalk between the brain and innate immune system may be dysregulated in systemic lupus erythematosus (SLE), a chronic autoimmune disease that presents with dysautonomia and aberrant inflammation. The hypothalamic-pituitary-adrenal (HPA) axis is an endogenous neuro-endocrine-immune pathway that can regulate inflammation following activation of [...] Read more.
Crosstalk between the brain and innate immune system may be dysregulated in systemic lupus erythematosus (SLE), a chronic autoimmune disease that presents with dysautonomia and aberrant inflammation. The hypothalamic-pituitary-adrenal (HPA) axis is an endogenous neuro-endocrine-immune pathway that can regulate inflammation following activation of vagal afferents. We hypothesized that chronic inflammatory processes in SLE are in part due to HPA axis dysfunction, at the level of either the afferent vagal-paraventricular nuclei (PVN) interface, the anterior pituitary, and/or at the adrenal glands. To study this, we challenged female control and SLE mice with lipopolysaccharide (LPS) and measured c-Fos expression as an index of neuronal activation, plasma adrenocorticotrophic hormone (ACTH) as an index of anterior pituitary function, and plasma corticosterone as an index of adrenal function. We found that c-Fos expression in the PVN, and plasma ACTH and corticosterone were comparable between unchallenged SLE and control mice. PVN c-Fos was increased similarly in control and SLE mice three hours after LPS challenge; however, there were no changes in plasma ACTH amongst any experimental groups post inflammatory challenge. Plasma corticosterone was markedly increased in LPS-challenged SLE mice compared to their vehicle-treated counterparts, but not in controls. Paradoxically, following LPS challenge, brain and spleen TNF-α were elevated in LPS-challenged SLE mice despite heightened plasma corticosterone. This suggests that, despite normal c-Fos expression in the PVN and activation of the HPA axis following LPS challenge, this cumulative response may not adequately defend SLE mice against inflammatory stimuli, leading to abnormally heightened innate immune responses and peripheral inflammation. Full article
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14 pages, 10674 KiB  
Article
Connexin 43 Controls the Astrocyte Immunoregulatory Phenotype
Brain Sci. 2018, 8(4), 50; https://doi.org/10.3390/brainsci8040050 - 22 Mar 2018
Cited by 14 | Viewed by 5719
Abstract
Astrocytes are the most abundant glial cells of the central nervous system and have recently been recognized as crucial in the regulation of brain immunity. In most neuropathological conditions, astrocytes are prone to a radical phenotypical change called reactivity, which plays a key [...] Read more.
Astrocytes are the most abundant glial cells of the central nervous system and have recently been recognized as crucial in the regulation of brain immunity. In most neuropathological conditions, astrocytes are prone to a radical phenotypical change called reactivity, which plays a key role in astrocyte contribution to neuroinflammation. However, how astrocytes regulate brain immunity in healthy conditions is an understudied question. One of the astroglial molecule involved in these regulations might be Connexin 43 (Cx43), a gap junction protein highly enriched in astrocyte perivascular endfeet-terminated processes forming the glia limitans. Indeed, Cx43 deletion in astrocytes (Cx43KO) promotes a continuous immune recruitment and an autoimmune response against an astrocyte protein, without inducing any brain lesion. To investigate the molecular basis of this unique immune response, we characterized the polysomal transcriptome of hippocampal astrocytes deleted for Cx43. Our results demonstrate that, in the absence of Cx43, astrocytes adopt an atypical reactive status with no change in most canonical astrogliosis markers, but with an upregulation of molecules promoting immune recruitment, complement activation as well as anti-inflammatory processes. Intriguingly, while several of these upregulated transcriptional events suggested an activation of the γ-interferon pathway, no increase in this cytokine or activation of related signaling pathways were found in Cx43KO. Finally, deletion of astroglial Cx43 was associated with the upregulation of several angiogenic factors, consistent with an increase in microvascular density in Cx43KO brains. Collectively, these results strongly suggest that Cx43 controls immunoregulatory and angiogenic properties of astrocytes. Full article
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