Abstract：
:Narcolepsy type 1 is a lifelong sleep disorder characterized by the loss of hypocretin-producing neurons in the brain. Environmental agents, including influenza, neurotoxic metals, and combustion smoke, have been implicated in the pathogenesis, especially in carriers of the human leukocyte antigen class II DQB1*06:02 allele. Sensitive experimental approaches have recently revealed hypocretin-autoreactive CD4+ and CD8+ T cells in the blood of narcoleptic patients. However, such potentially harmful cells are also detectable, to a lesser degree, in control DQB1*06:02 carriers, suggesting that the integrity of the blood-brain barrier (BBB) provides a neuroprotective effect. Here, we present the hypothesis that external toxic agents induce neuroinflammation in the olfactory bulb and concomitant overproduction of proinflammatory cytokines (e.g., tumor necrosis factor-α and interferon-γ); this, in turn, compromises the BBB, allowing autoimmune cells to access and kill hypocretinergic neurons. Such sequential pathological alterations could occur insidiously, passing unnoticed and consequently being underestimated. The elevated number of autoreactive T cells in narcoleptics relative to controls might reflect externally induced immunomodulation rather than a direct disease trigger.
journal_name
Med Hypothesesjournal_title
Medical hypothesesauthors
Mori Idoi
10.1016/j.mehy.2019.109294subject
Has Abstractpub_date
2019-10-01 00:00:00pages
109294eissn
0306-9877issn
1532-2777pii
S0306-9877(19)30445-1journal_volume
131pub_type
杂志文章abstract：:Pulseless electrical activity occurs when organised or semi-organised electrical activity of the heart persists but the product of systemic vascular resistance and the increase in systemic arterial flow generated by the ejection of the left venticular stroke volume is not sufficient to produce a clinically detectable ...
journal_title：Medical hypotheses
pub_type： 杂志文章
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pub_type： 杂志文章
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journal_title：Medical hypotheses
pub_type： 杂志文章
doi：10.1016/j.mehy.2008.04.013
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journal_title：Medical hypotheses
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journal_title：Medical hypotheses
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journal_title：Medical hypotheses
pub_type： 社论
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journal_title：Medical hypotheses
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journal_title：Medical hypotheses
pub_type： 杂志文章
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pub_type： 杂志文章
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journal_title：Medical hypotheses
pub_type： 杂志文章
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journal_title：Medical hypotheses
pub_type： 历史文章,杂志文章
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journal_title：Medical hypotheses
pub_type： 杂志文章
doi：10.1016/j.mehy.2003.10.017
更新日期：2004-01-01 00:00:00
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pub_type： 杂志文章
doi：10.1016/0306-9877(87)90058-2
更新日期：1987-08-01 00:00:00
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journal_title：Medical hypotheses
pub_type： 杂志文章
doi：10.1016/j.mehy.2007.04.003
更新日期：2007-01-01 00:00:00
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journal_title：Medical hypotheses
pub_type： 杂志文章
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journal_title：Medical hypotheses
pub_type： 杂志文章
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更新日期：2006-01-01 00:00:00
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journal_title：Medical hypotheses
pub_type： 杂志文章
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journal_title：Medical hypotheses
pub_type： 杂志文章
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journal_title：Medical hypotheses
pub_type： 杂志文章
doi：10.1054/mehy.1998.0756
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journal_title：Medical hypotheses
pub_type： 杂志文章
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pub_type： 杂志文章
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journal_title：Medical hypotheses
pub_type： 杂志文章
doi：10.1016/j.mehy.2008.04.020
更新日期：2008-09-01 00:00:00
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journal_title：Medical hypotheses
pub_type： 杂志文章
doi：10.1016/j.mehy.2011.04.023
更新日期：2011-08-01 00:00:00
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journal_title：Medical hypotheses
pub_type： 杂志文章
doi：10.1016/s0306-9877(03)00325-6
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journal_title：Medical hypotheses
pub_type： 杂志文章
doi：10.1016/j.mehy.2004.12.018
更新日期：2005-01-01 00:00:00
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journal_title：Medical hypotheses
pub_type： 杂志文章
doi：10.1016/j.mehy.2020.110073
更新日期：2020-10-01 00:00:00
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journal_title：Medical hypotheses
pub_type： 杂志文章
doi：10.1016/j.mehy.2016.05.010
更新日期：2016-08-01 00:00:00
