Article

The Blood–Brain Barrier in Psychoneuroimmunology

Geriatrics Research Education and Clinical Center, Veterans Affairs Medical Center-St. Louis, 915 North Grand Boulevard, St. Louis, MO 63106, USA.
Immunology and allergy clinics of North America (Impact Factor: 1.82). 06/2009; 29(2):223-8. DOI: 10.1016/j.iac.2009.02.001
Source: PubMed

ABSTRACT

The term ''psychoneuroimmunology'' connotes separate compartments that interact. The blood-brain barrier (BBB) is both the dividing line, physical and physiologic, between the immune system and the central nervous system (CNS) and the locale for interaction. The BBB restricts unregulated mixing of immune substances in the blood with those in the CNS, directly transports neuroimmune-active substances between the blood and CNS, and itself secretes neuroimmune substances. These normal functions of the BBB can be altered by neuroimmune events. As such, the BBB is an important conduit in the communication between the immune system and the CNS.

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    • "Although the CNS is isolated from the peripheral immune system by the blood–brain barrier (BBB), it is possible for cytokines to invade the CNS under normal physiological conditions (Banks, 2005). For example, activated maternal pro-inflammatory cytokines such as IL-1β, TNF-α, and IL-6 can invade the fetal CNS through various pathways (Banks, 2006). The possible mechanisms by which cytokines cross the BBB are saturable transport (Banks et al., 1989; Osburg et al., 2002), disruption of the BBB (Quagliarello et al., 1991), and through circumventricular organs that lack the BBB (Buller, 2001). "
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    ABSTRACT: Schizophrenia is a serious mental illness with chronic symptoms and significant impairment in psychosocial functioning. Although novel antipsychotics have been developed, the negative and cognitive symptoms of schizophrenia are still unresponsive to pharmacotherapy. The high level of social impairment and a chronic deteriorating course suggest that schizophrenia likely has neurodegenerative characteristics. Inflammatory markers such as pro-inflammatory cytokines are well-known etiological factors for psychiatric disorders, including schizophrenia. Inflammation in the central nervous systemis closely related to neurodegeneration. In addition to pro-inflammatory cytokines, microglia also play an important role in the inflammatory process in the CNS. Uncontrolled activity of pro-inflammatory cytokines and microglia can induce schizophrenia in tandem with genetic vulnerability and glutamatergic neurotransmitters. Several studies have investigated the possible effects of antipsychotics on inflammation and neurogenesis. Additionally, anti-inflammatory adjuvant therapy has been under investigation as a treatment option for schizophrenia. Further studies should consider the confounding effects of systemic factors such as metabolic syndrome and smoking. In addition, the unique mechanisms by which pro-inflammatory cytokines are involved in the etiopathology of schizophrenia should be investigated. In this article, we aimed to review(1) major findings regarding neuroinflammation and pro-inflammatory cytokine alterations in schizophrenia, (2) interactions between neuroinflammation and neurogenesis as possible neural substrates for schizophrenia, and (3) novel pharmacological approaches.
    Full-text · Article · Jun 2015 · Progress in Neuro-Psychopharmacology and Biological Psychiatry
    • "A pivotal mechanism for compromised central nervous system (CNS) functioning by peripheral inflammation is the induction of neuroinflammation (Dantzer et al., 2008). Suggested mechanisms for the propagation of peripheral inflammation into the CNS include the stimulation of vagal nerve afferents (Bluthe et al., 1994), the transport of cytokines across the blood brain barrier (BBB) (Banks, 2006), and altered nitric oxide (NO) metabolism leading to BBB breakdown (Najjar et al., 2013). However, it remains elusive which distinct type of peripheral inflammation induces depressive state, triggers neuroinflammation, and potentially affects hippocampal structures and functions. "
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    ABSTRACT: Chronic peripheral inflammation mediated by cytokines such as TNFα, IL-1β, and IL-6 is associated with psychiatric disorders like depression and anxiety. However, it remains elusive which distinct type of peripheral inflammation triggers neuroinflammation and affects hippocampal plasticity resulting in depressive-like behavior. We hypothesized that chronic peripheral inflammation in the human TNF-α transgenic (TNFtg) mouse model of rheumatoid arthritis spreads into the central nervous system and induces depressive state manifested in specific behavioral pattern and impaired adult hippocampal neurogenesis. TNFtg mice showed severe erosive arthritis with increased IL-1β and IL-6 expression in tarsal joints with highly elevated human TNF-α levels in the serum. Intriguingly, IL-1β and IL-6 mRNA levels were not altered in the hippocampus of TNFtg mice. In contrast to the pronounced monocytosis in joints and spleen of TNFtg mice, signs of hippocampal microgliosis or astrocytosis were lacking. Furthermore, locomotion was impaired, but there was no locomotion-independent depressive behavior in TNFtg mice. Proliferation and maturation of hippocampal neural precursor cells as well as survival of newly generated neurons were preserved in the dentate gyrus of TNFtg mice despite reduced motor activity and peripheral inflammatory signature. We conclude that peripheral inflammation in TNFtg mice is mediated by chronic activation of the innate immune system. However, severe peripheral inflammation, though impairing locomotor activity, does not elicit depressive-like behavior. These structural and functional findings indicate the maintenance of hippocampal immunity, cellular plasticity, and behavior despite peripheral innate inflammation. Copyright © 2015. Published by Elsevier Inc.
    No preview · Article · Jun 2015 · Brain Behavior and Immunity
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    • "Based on the possibility that peripheral cytokines can move into the CNS via the blood brain-barrier (BBB) (Banks, 2006), many studies have measured peripheral cytokine levels as indirect "
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    ABSTRACT: BACKGROUND: Despite the substantial role of the cytokine network in depression and suicide, few studies have investigated the role of genetic polymorphisms of pro- and anti-inflammatory cytokines in suicide in major depressive disorder (MDD). The aim of this study was to investigate whether tumor necrosis factor-alpha (TNF-alpha) -308G>A, interferon-gamma (IFN-gamma) +874A>T, and interleukin-10 retain-->(IL-10) -1082A>G are associated with increased risk for suicide attempts in MDD. METHODS: Among patients with MDD, 204 patients who had attempted suicide and 97 control patients who had not attempted suicide were recruited. A chi-square test was used to identify a possible risk genotype or allele type for suicide. A subsequent multivariate logistic regression analysis was conducted to investigate the influence of a risk genotype or allele type adjusted for other environmental factors. retain-->The lethality of the suicide attempt was also tested between genotype and allele types among suicidal patients with MDD. RESULTS: The GG genotype of the TNF-alpha -308G>A polymorphism was found to significantly increase risk for suicide attempt (adjusted OR=2.630, 95% CI=1.206 to 5.734). IFN-gamma +874A>T and IL-10 -1082A>G were not associated with risk for suicide. Lethality of the suicide attempt was not associated with any of the three cytokine genotypes or allele types. LIMITATIONS: Limitations include a relatively small sample size and a cross-sectional design. CONCLUSIONS: TNF-alpha -308G>A polymorphism is an independent risk factor for suicide attempts in MDD. Future studies should clarify the neural mechanisms by which the GG genotype of TNF-alpha -308G>A influences suicide in MDD.
    Full-text · Article · Apr 2013 · Journal of Affective Disorders
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