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Systemic LPS administration induces brain inflammation but not dopaminergic neuronal death in the substantia nigra

Authors:
Heykyeong Jeong at GlaxoSmithKline
Heykyeong Jeong
Ilo Jou
Ilo Jou
Ilo Jou
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Eun-hye Joe
Eun-hye Joe
Eun-hye Joe
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It has been suggested that brain inflammation is important in aggravation of brain damage and/or that inflammation causes neurodegenerative diseases including Parkinson's disease (PD). Recently, systemic inflammation has also emerged as a risk factor for PD. In the present study, we evaluated how systemic inflammation induced by intravenous (iv) lipopolysaccharides (LPS) injection affected brain inflammation and neuronal damage in the rat. Interestingly, almost all brain inflammatory responses, including morphological activation of microglia, neutrophil infiltration, and mRNA/protein expression of inflammatory mediators, appeared within 4-8 h, and subsided within 1-3 days, in the substantia nigra (SN), where dopaminergic neurons are located. More importantly, however, dopaminergic neuronal loss was not detectable for up to 8 d after iv LPS injection. Together, these results indicate that acute induction of systemic inflammation causes brain inflammation, but this is not sufficiently toxic to induce neuronal injury.
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  • May 2024
  • INT J MOL SCI
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  • Oct 2023
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... It could also affect the dopaminergic neurotransmission in experimental studies on Parkinsonism Duty and Jenner, 2011;Felger and Miller, 2012). Intracranial / intraperitoneal injection of lipopolysaccharide that activates immune cells and enhances inflammation has been found to damage dopaminergic neurons in the nigrostriatal region (He et al., 2013;Jeong et al., 2010). Activation of TLRs and NF-kβ pathway has also been observed in mouse model of PD (Noelker et al., 2013). ...
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Article
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  • NEUROTOXICOLOGY
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Article
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Article
Full-text available
  • Dec 2022
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... To validate the model, we first used an established rat paradigm of inflammation based on intracerebral lipopolysaccharide (LPS) administration (16). In this paradigm, neuronal viability and morphology are preserved, while inducing microglial activation within a few hours, and a delayed astrocytic response that is detectable only 24 hours after injection (17). Therefore, glial responses can be transiently dissociated from neuronal degeneration, and the signature of reactive microglia investigated independently of any astrogliosis. ...
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Article
Full-text available
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View
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View
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Short communication Interleukin6 levels in cerebrospinal fluid inversely correlate to severity of Parkinson's disease
Article
Introduction - Several lines of evidence suggest that neuroimmune mechanisms may also be involved in neurodegeneration in Parkinson's disease (PD). The potential role of cytokines such as interleukin 6 (IL-6), in the interaction between neurons and immune system has been emphasized by recent findings. IL-6 induces acute phase protein synthesis, differentiation of neuronal cells and improves catecholaminergic and cholinergic cell survival in the brain. Subjects and methods - We determined levels of IL-6 in cerebrospinal fluid (CSF) of untreated parkinsonian patients and age- and sex-matched controls. Intensity of disease was evaluated by the Unified Parkinson's Disease Rating scale. Results - Significantly elevated levels of IL-6 were found in the CSF of parkinsonian patients. Moreover a significant inverse correlation between severity of PD and IL-6 CSF levels appeared. Discussion - Elevated IL-6 levels in the CSF of untreated parkinsonian patients may reflect the original condition in the course of disease. We speculate that an endogenous upregulation of IL-6 synthesis occurs in order to regenerate lesioned neurons probably at an early phase of the degenerative process in PD.
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