Innate immunity: The missing link in neuroprotection and neurodegeneration? Nat Rev Neurosci

Centre for Research in Neurosciences, McGill University, The Montréal General Hospital Research Institute, Montréal, Québec, H3G 1A4, Canada.
Nature reviews Neuroscience (Impact Factor: 31.43). 04/2002; 3(3):216-27. DOI: 10.1038/nrn752
Source: PubMed


Innate immunity was previously thought to be a nonspecific immunological programme that was engaged by peripheral organs to maintain homeostasis after stress and injury. Emerging evidence indicates that this highly organized response also takes place in the central nervous system. Through the recognition of neuronal fingerprints, the long-term induction of the innate immune response and its transition to an adaptive form might be central to the pathophysiology and aetiology of neurodegenerative disorders. Paradoxically, this response also protects neurons by favouring remyelination and trophic support afforded by glial cells.

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    • "generates blood–brain barrier infiltration, a leading cause of PM entry into the brain (Nguyen et al., 2002). The direct contact of PM to profound areas of brain would be a direct source of oxidative stress to neuronal cells and could increment the neurological effects of PM. "
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    ABSTRACT: Several experimental and epidemiological studies have demonstrated the neurological adverse effects caused by exposure to air pollution, specifically in relation to pollutant particulate matter (PM). The objective of this study was to investigate the direct effect of PM in increased concentrations in different brain regions, as well as the mechanisms involving its neurotoxicity, by evaluating oxidative stress parameters in vitro. Olfactory bulb, cerebral cortex, striatum, hippocampus and cerebellum of rats were homogenized and incubated with PM < 2.5 μm of diameter (PM2.5) at concentrations of 3, 5 and 10 µg/mg of tissue. The oxidative damage caused by lipid peroxidation of these structures was determined by testing the thiobarbituric acid reactive species (TBA-RS). In addition, we measured the activity of antioxidant enzyme catalase (CAT) and superoxide dismutase (SOD). All PM concentrations were able to damage the cerebellum and hippocampus, strongly enhancing the lipid peroxidation in both structures. PM incubation also decreased the CAT activity of the hippocampus, cerebellum, striatum and olfactory bulb, though it did not generate higher levels of lipid peroxidation in either of the last two structures. PM incubation did not alter any measurement of the cerebral cortex. The cerebellum and hippocampus seem to be more susceptible than other brain structures to in vitro direct PM exposure assay and the oxidative stress pathway catalyzes the neurotoxic effect of PM exposure, as evidenced by high consumption of CAT and high levels of TBA-RS. Thus, PM direct exposure seems to activate toxic neurological effects.
    Inhalation Toxicology 09/2015; 27(10):1-6. DOI:10.3109/08958378.2015.1060278 · 2.26 Impact Factor
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    • "However, other studies demonstrate that IL-1b can play an important role in protection and repair (Albrecht et al., 2002; Carlson et al., 1999; John et al., 2005; Saavedra et al., 2007; Wang et al., 1994). It may do both by modifying astrocyte behavior (Nguyen et al., 2002; Zhao and Schwartz, 1998). "
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    ABSTRACT: Astrocytes produce and export the antioxidant glutathione (GSH). Previously, we found that interleukin-1β (IL-1β) enhanced the expression of astrocyte system xc (-) , the transporter that delivers the rate-limiting substrate for GSH synthesis-cyst(e)ine. Herein, we demonstrate directly that IL-1β mediates a time-dependent increase in extracellular GSH levels in cortical astrocyte cultures, suggesting both enhanced synthesis and export. This increased GSH production was blocked by inhibition of nuclear factor-κB (NF-κB) activity but not by inhibition of p38 MAPK. To determine whether this increase could provide protection against oxidative stress, the oxidants tert-butyl hydroperoxide (tBOOH) and ferrous sulfate (FeSO4 ) were employed. IL-1β treatment prevented the increase in reactive oxygen species produced in astrocytes following tBOOH exposure. Additionally, the toxicity induced by tBOOH or FeSO4 exposure was significantly attenuated following treatment with IL-1β, an effect reversed by concomitant exposure to l-buthionine-S,R-sulfoximine (BSO), which prevented the IL-1β-mediated rise in GSH production. IL-1β failed to increase GSH or to provide protection against t-BOOH toxicity in astrocyte cultures derived from IL-1R1 null mutant mice. Overall, our data indicate that under certain conditions IL-1β may be an important stimulus for increasing astrocyte GSH production, and potentially, total antioxidant capacity in brain, via an NF-κB-dependent process. GLIA 2015. © 2015 Wiley Periodicals, Inc.
    Glia 04/2015; 63(9). DOI:10.1002/glia.22828 · 6.03 Impact Factor
    • "The innate/adaptive immunity have been implicated in epilepsy; microglia , astrocytes and neurons are believed to contribute to the innate immunitytype processes causing brain's inflammation (Vezzani et al. 2011b). The activation of innate immunity and the transition to adaptive immunity are mediated by a large variety of inflammatory mediators, including cytokines-polypeptides, which play a pivotal role (Nguyen et al. 2002; Vezzani et al. 2011a, c). Cytokines are released by immunocompetent and endothelial cells, as well as by glia and neurons in the CNS, thereby enabling communication between effector and target cells during an immune challenge or tissue injury (Vezzani et al. 2011b). "
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    ABSTRACT: It is widely acknowledged that immune system influences several aspects of the central nervous system. Literature data have shown that immune system and autoimmune response play an important role in the pathogenesis of several neurodegenerative/neurological diseases (i.e Parkinson’s and Alzheimer’s Diseases, Multiple Sclerosis). However, very recent evidences of specific antibodies found in epileptic encephalitis, the good response to immune therapy in refractory epileptic syndromes and the strong relationship between systemic autoimmune disease and epilepsy suggest a plausible role for the immune system also in paroxysmal neurological disorders. In fact, an immune hypothesis represents a new way to approach epilepsy and could contribute to clarify several unanswered questions in the next future. In this review, we analysed these points mimicking a tour around current evidences from experimental animal models to clinical suggestions.
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