CSF hypocretin measures in patients with obstructive sleep apnea

Kanbayashi, Takashi; Inoue, Yuichi; Kawanishi, K.; Takasaki, Hideki; Aizawa, Rika; Takahashi, Ken­ichi; Ogawa, Yasuaki; Abe, Masahito; Hishikawa, Yasuo; Shimizu, Tetsuo

doi:10.1046/j.0962-1105.2003.00373.x

Cited by 32 publications

(5 citation statements)

References 13 publications

Supporting

Mentioning

Contrasting

Order By: Relevance

“…extrapolation of csf hcrt-1 results have previously been hampered by the inter-assay variability of the available radioimmunoassay and different definitions of hypocretin deficiency (i.e., all values under the local normal area, 15 detectable versus undetectable levels 14 or < 110 pg/mL as a fixed standard 3 ). considering the variable normal mean values and consequently variable low cutoff limits of individual laboratories (88-149 pg/mL, Tables 3 and 4), a fixed standard value for hypocretin deficiency (which is proposed as a possibility by icsd-2) is obviously currently problematic.…”

Section: Discussionmentioning

confidence: 99%

“…it was possible to include 7 studies of Nc patients 5,6,8,[13][14][15][16] and 5 studies of Nwc patients 5,6,8,15,17 through the medliNe search. sixteen eligible studies were excluded because they overlapped § Significantly lower mean CSF hcrt-1 value compared to all other groups (P < 0.0001).…”

Section: Other Narcolepsy Populations Compared With the Danish Populationmentioning

confidence: 99%

See 1 more Smart Citation

Validation of the ICSD-2 Criteria for CSF Hypocretin-1 Measurements in the Diagnosis of Narcolepsy in the Danish Population

Knudsen

Jennum

Alving

et al. 2010

Sleep

View full text Add to dashboard Cite

show abstract

Section: Discussionmentioning

confidence: 99%

Section: Other Narcolepsy Populations Compared With the Danish Populationmentioning

confidence: 99%

Validation of the ICSD-2 Criteria for CSF Hypocretin-1 Measurements in the Diagnosis of Narcolepsy in the Danish Population

Knudsen

Jennum

Alving

et al. 2010

Sleep

View full text Add to dashboard Cite

show abstract

“…Human narcolepsy is thought to be caused by degeneration of orexin-containing neurons (44), and narcolepsy patients have a high incidence of sleep apnea (6). Some OSA patients show low levels of plasma orexin (4,38), although an opposite result (15) and no change in CSF orexin (16) have also been reported. Because human sleep apnea is characterized by chronic IH, lack of LTF may enhance the incidence of sleep apnea, although acute IH in this study did not increase sleep apnea in ORX-KO mice.…”

Section: Discussionmentioning

confidence: 99%

Ventilatory long-term facilitation in mice can be observed during both sleep and wake periods and depends on orexin

Terada¹,

Nakamura²,

Zhang³

et al. 2008

Journal of Applied Physiology

View full text Add to dashboard Cite

Respiratory long-term facilitation (LTF) is a long-lasting (>1 h) augmentation of respiratory motor output that occurs even after cessation of hypoxic stimuli, is serotonin-dependent, and is thought to prevent sleep-disordered breathing such as sleep apnea. Raphe nuclei, which modulate several physiological functions through serotonin, receive dense projections from orexin-containing neurons in the hypothalamus. We examined possible contributions of orexin to ventilatory LTF by measuring respiration in freely moving prepro-orexin knockout mice (ORX-KO) and wild-type (WT) littermates before, during, and after exposure to intermittent hypoxia (IH; 5 x 5 min at 10% O2), sustained hypoxia (SH; 25 min at 10% O2), or sham stimulation. Respiratory data during quiet wakefulness (QW), slow wave sleep (SWS), and rapid-eye-movement sleep were separately calculated. Baseline ventilation before hypoxic stimulation and acute responses during stimulation did not differ between the ORX-KO and WT mice, although ventilation depended on vigilance state. Whereas the WT showed augmented minute ventilation (by 20.0 +/- 4.5% during QW and 26.5 +/- 5.3% during SWS; n = 8) for 2 h following IH, ORX-KO showed no significant increase (by -3.1 +/- 4.6% during QW and 0.3 +/- 5.2% during SWS; n = 8). Both genotypes showed no LTF after SH or sham stimulation. Sleep apnea indexes did not change following IH, even when LTF appeared in the WT mice. We conclude that LTF occurs during both sleep and wake periods, that orexin is necessary for eliciting LTF, and that LTF cannot prevent sleep apnea, at least in mice.

show abstract

“…However, the development of sleep apnoea may itself be a side effect of a defect in the orexin system. For example, there are numerous studies indicating that orexin levels are reduced in patients suffering from sleep apnoea (Refs 55, 56, 57, 58, 59). Similarly, patients with Guillain–Barré syndrome, who display respiratory paralysis, have significantly reduced orexin concentration in their cerebrospinal fluid (Ref.…”

Section: Discussionmentioning

confidence: 99%

Hypothalamic orexins/hypocretins as regulators of breathing

Williams

Burdakov

2008

Expert Rev. Mol. Med.

View full text Add to dashboard Cite

It was suggested half a century ago that electrical impulses from the lateral hypothalamic area stimulate breathing. It is now emerging that these effects may be mediated, at least in part, by neurons containing orexin neuropeptides (also known as hypocretins). These cells promote wakefulness and consciousness, and their loss results in narcolepsy. Recent data also show that orexin neurons directly project to respiratory centres in the brainstem, which express orexin receptors, and where injection of orexin stimulates breathing. Because orexin neurons receive inputs that signal metabolic, sleep/wake and emotional states, it is tempting to speculate that they may regulate breathing according to these parameters. Knockout of the orexin gene in mice reduces CO 2 -induced increases in breathing by ~50% and increases the frequency of spontaneous sleep apneas. The relationship between orexins and breathing may be bidirectional: the rate of breathing controls acid and CO 2 levels, and these signals alter the electrical activity of orexin neurons in vitro. Overall, these findings suggest that orexins are important for the regulation of breathing and may potentially play a role in the pathophysiology and medical treatment of respiratory disorders.The brains of higher animals perform a staggering array of tasks at the same time, posing a fundamental control problem: how does the brain arrange different actions to generate meaningful behaviour? For example, how does it generate a heightened state of alertness when needed, such as during hunger, but reduce wakefulness when it may not be translated into efficient outcomes, for example during darkness? The hypothalamus, an almond-sized area of the brain in humans, has long been recognised as a fundamental orchestrator of diverse behaviours and adaptive responses (Refs 1, 2). This neuron-dense structure integrates a wide range of peripheral and sensory signals, while interfacing with a multitude of circuits with more specialised functions. Recently, hypothalamic cells containing orexins (also known as hypocretins; HCRTs) have emerged as critical and multifaceted players in hypothalamic behavioural co-ordination. In this article, we review recent data suggesting that orexin neurons are important for a successful partnership between arousal states and changes in ventilation. Orexins: arousal signals from the lateral hypothalamic areaOrexins are a pair of peptide neurotransmitters (orexin-A and -B) produced from the same precursor (Refs 3,4 The lateral hypothalamic area and breathing: historical linksThe involvement of the lateral hypothalamus in both cognitive arousal and breathing was recognised many decades ago. In the 1920s, the Viennese neurologist Constantin von Economo performed post-mortem studies of brain lesions of patients with encephalitis lethargica, and predicted that the lateral hypothalamus is the source of a critical wakepromoting signal, now thought to come from orexin neurons (reviewed in detail in Ref. 23).In relation to breathing, a key prediction of...

show abstract

CSF hypocretin measures in patients with obstructive sleep apnea

Cited by 32 publications

References 13 publications

Validation of the ICSD-2 Criteria for CSF Hypocretin-1 Measurements in the Diagnosis of Narcolepsy in the Danish Population

Validation of the ICSD-2 Criteria for CSF Hypocretin-1 Measurements in the Diagnosis of Narcolepsy in the Danish Population

Ventilatory long-term facilitation in mice can be observed during both sleep and wake periods and depends on orexin

Hypothalamic orexins/hypocretins as regulators of breathing

Contact Info

Product

Resources

About