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Insomnia, hypersomnia and coma in animal models and their clinical implications

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Abstract

Economo observed in 1930 that many cases of lethargy begin with a severe insomnia and fever followed by a long-lasting hypersomnia. We confirmed this evidence in animal cases where chemical lesions of the preoptic region resulted in severe insomnia accompanied with fever. Moreover, a subsequent pharmacological inhibition of neuronal activity of the posterior ventrolateral hypothalamus caused transient hypersomnia in these insomniac animals. However, vigilance states of the experimental animals returned to normal after several weeks, suggesting that the irreversible Economo’s lethargy may be due to the damage of passing fibers in the ventral hypothalamus. Similarly, chemical lesions of neurons of the midbrain reticular formation did not induce coma nor hypersomnia, which is inconsistent with lesion studies reported by Lindsley et al. using electrolytic coagulation. This fact further supports the importance of passing fibers in the midbrain. In addition, Mauthner in 1890 observed hypersomnia and abnormal eye movements in lethargic patients infected by “nona”, suggesting the implication of the periaqueductal gray in the vicinity of the 3rd nerve. We confirmed this hypothesis: hypersomnia was accompanied by a significant increase in REM sleep after chemical inactivation of a small part of the ventrolateral periaqueductal gray and dorsal portion of the subjacent reticular formation. On the other hand, removal of the tele- and di-encephalon caused an irreversible coma and abolished the daily rhythm of REM. This state of sleep is also regulated by forebrain structures and internal clocks in the suprachiasmatic nucleus.

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Authors and Affiliations

  1. Sleep Disorder Research Project, Tokyo Institute of Psychiatry, Tokyo Metropolitan Organization for Medical Research, Tokyo, Japan

    Kunio Kitahama &  Pierre-Hervé Luppi

  2. Site Laennec, CNRS UMR5167, 7–11 rue Guillaume Paradin, 69372, Lyon Cedex 08, France

    Kunio Kitahama &  Pierre-Hervé Luppi

Authors
  1. Kunio Kitahama
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  2. Pierre-Hervé Luppi
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Correspondence to Pierre-Hervé Luppi.

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Kitahama, K., Luppi, PH. Insomnia, hypersomnia and coma in animal models and their clinical implications. Sleep Biol. Rhythms 9 (Suppl 1), 52–58 (2011). https://doi.org/10.1111/j.1479-8425.2010.00462.x

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