Inflammation and the brain

Compston, Alastair

doi:10.1007/bf03160168

Cited by 15 publications

(5 citation statements)

References 63 publications

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“…Microglia apparently possess the ability to alter their phenotype, a feature that enables them to respond differently to different stimuli, or to the same stimulus if it coexists with an additional stimulus that precedes or follows it (Perry and Gordon, 1988;Graeber and Streit, 1990;Perry and Andersson, 1992;Banati et al, 1993;Compston, 1993;Gehrmann et al, 1995;Kiefer et al, 1995;Kreutzberg, 1995;Paakkari and Lindsberg, 1995;Schwartz et al, 2006). In line with our concept of protective autoimmunity, we suggest that the microglia function as local sentinels.…”

Section: The Mechanism Underlying Protective Autoimmunitysupporting

confidence: 59%

Does Inflammation in an Autoimmune Disease Differ from Inflammation in Neurodegenerative Diseases? Possible Implications for Therapy

Schwartz

Butovsky

Kipnis

2006

Jrnl NeuroImmune Pharm

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Accumulating evidence suggests that neurodegenerative diseases of the central nervous system (CNS) are associated with a local inflammatory response. CNS autoimmune diseases are also associated with inflammation. Does this mean that all neurodegenerative diseases are autoimmune in nature? Does it imply that autoimmune and neurodegenerative diseases are both eligible for the same therapy? What distinguishes between the two types of disease? Do they differ both in etiology and in pathology, or do they have different etiologies but similar pathology and progression? In this minireview we offer a new view of the inflammatory differences between neurodegenerative and autoimmune diseases in the CNS and discuss the implications for therapy.

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Section: The Mechanism Underlying Protective Autoimmunitysupporting

confidence: 59%

Does Inflammation in an Autoimmune Disease Differ from Inflammation in Neurodegenerative Diseases? Possible Implications for Therapy

Schwartz

Butovsky

Kipnis

2006

Jrnl NeuroImmune Pharm

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“…In that moment, the fact that many cases of PD were accompanied with a general brain inflammation along with the neurodegeneration was pointed out [14, 17, 18]. The dramatic proliferation of reactive amoeboid macrophages and microglia seen in the SN of parkinsonian brains, together with oxidative stress, was highly compatible with the existence of an inflammatory process similar to that previously described for Alzheimer's disease (AD) [19] and multiple sclerosis [20]. …”

Section: Introductionmentioning

confidence: 67%

Inflammatory Animal Model for Parkinson's Disease: The Intranigral Injection of LPS Induced the Inflammatory Process along with the Selective Degeneration of Nigrostriatal Dopaminergic Neurons

et al. 2011

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We have developed an animal model of degeneration of the nigrostriatal dopaminergic neurons, the neuronal system involved in Parkinson's disease (PD). The implication of neuroinflammation on this disease was originally established in 1988, when the presence of activated microglia in the substantia nigra (SN) of parkinsonians was reported by McGeer et al. Neuroinflammation could be involved in the progression of the disease or even has more direct implications. We injected 2 μg of the potent proinflammatory compound lipopolysaccharide (LPS) in different areas of the CNS, finding that SN displayed the highest inflammatory response and that dopaminergic (body) neurons showed a special and specific sensitivity to this process with the induction of selective dopaminergic degeneration. Neurodegeneration is induced by inflammation since it is prevented by anti-inflammatory compounds. The special sensitivity of dopaminergic neurons seems to be related to the endogenous dopaminergic content, since it is overcome by dopamine depletion. Compounds that activate microglia or induce inflammation have similar effects to LPS. This model suggest that inflammation is an important component of the degeneration of the nigrostriatal dopaminergic system, probably also in PD. Anti-inflammatory treatments could be useful to prevent or slow down the rate of dopaminergic degeneration in this disease.

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“…In neuron-glia cultures, microglial activation has been associated with neurodegeneration induced by LPS, the human immunodeficiency virus-1 coat protein gp120, ␤-amyloid peptides, and the pesticide rotenone (Boje and Arora, 1992;Chao et al, 1992;Dawson et al, 1993;Dickson et al, 1993;Ii et al, 1996;Jeohn et al, 1998;Liu et al, 2000a;Gao et al, 2002;Qin et al, 2002). In animal models and humans, microglial activation is frequently observed during the development of neurodegenerative diseases including PD, AD, amyotrophic lateral sclerosis, and multiple sclerosis, as well as reperfusion brain ischemia (McGeer et al, 1988;Compston, 1992;Rogers et al, 1992;Benveniste et al, 2001). Therefore, naloxone may have a broader than previously thought range of efficacy as a potential agent for the treatment of multiple disorders.…”

Section: Discussionmentioning

confidence: 99%

Inhibition by Naloxone Stereoisomers of β-Amyloid Peptide (1–42)-induced Superoxide Production in Microglia and Degeneration of Cortical and Mesencephalic Neurons

Liu¹,

Qin²,

Wilson³

et al. 2002

J Pharmacol Exp Ther

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Previously we reported that naloxone stereoisomers, in an opioid receptor-independent manner, attenuated the inflammation-mediated degeneration of dopaminergic neurons by inhibition of the activation of microglia, the resident immune cells in the brain. Recently we discovered that ␤-amyloid peptide A␤ (1-42) exhibited enhanced neurotoxicity toward both cortical and mesencephalic neurons through the activation of microglia and production of superoxide. The purpose of this study was to determine whether naloxone isomers had any effect on A␤ (1-42)-induced neurodegeneration. Pretreatment of either cortical or mesencephalic neuron-glia cultures with 1 to 10 M (Ϫ)-naloxone, prior to treatment for up to 11 days with 0.1 to 3 M A␤ (1-42), afforded significant neuroprotection as judged by neurotransmitter uptake, immunocytochemical analysis, and cell counting. More importantly, (ϩ)-naloxone, the ineffective enantiomer of (Ϫ)-naloxone in binding opioid receptors, was equally effective in affording neuroprotection. Mechanistically, inhibition of A␤ (1-42)-induced production of superoxide in microglia underlay the neuroprotective effect of naloxone stereoisomers. Moreover, neuroprotection and inhibition of A␤ (1-42)-induced superoxide production was also achieved with naloxone methiodide, a charged analog with quaternary amine, suggesting that the site of action for naloxone isomers is at the cell surface of microglia. These results demonstrated that naloxone isomers, through mechanisms unrelated to the opioid receptors, were capable of inhibiting A␤ (1-42)-induced microglial activation and degeneration of both cortical and mesencephalic neurons. Combined with our previous observations with inflammagen-induced neurodegeneration, naloxone analogs, especially (ϩ)-naloxone, may have potential therapeutic efficacy for the treatment of Alzheimer's and Parkinson's disease.

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Inflammation and the brain

Cited by 15 publications

References 63 publications

Does Inflammation in an Autoimmune Disease Differ from Inflammation in Neurodegenerative Diseases? Possible Implications for Therapy

Does Inflammation in an Autoimmune Disease Differ from Inflammation in Neurodegenerative Diseases? Possible Implications for Therapy

Inflammatory Animal Model for Parkinson's Disease: The Intranigral Injection of LPS Induced the Inflammatory Process along with the Selective Degeneration of Nigrostriatal Dopaminergic Neurons

Inhibition by Naloxone Stereoisomers of β-Amyloid Peptide (1–42)-induced Superoxide Production in Microglia and Degeneration of Cortical and Mesencephalic Neurons

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