Brain Blood Flow in Andean and Himalayan High-Altitude Populations: Evidence of Different Traits for the Same Environmental Constraint

Jansen, Gerard F. A.; Basnyat, Buddha

doi:10.1038/jcbfm.2010.150

Cited by 27 publications

(35 citation statements)

References 41 publications

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“…Consistent with previous studies (Jansen & Basnyat, ), highlanders, in particular CMS+, exhibited ∼30% lower cerebral perfusion, notwithstanding the interpretive constraints associated with TCD ultrasound (Liu et al . ) and corresponding decrease in CDO 2 that persisted even following correction for the independent vasoconstrictor effects of polycythaemia‐induced alteration in blood rheology and hypocapnia.…”

Section: Discussionsupporting

confidence: 91%

“…Consistent with previous studies (Jansen & Basnyat, 2011), highlanders, in particular CMS+, exhibited ß30% lower cerebral perfusion, notwithstanding the interpretive constraints associated with TCD ultrasound (Liu et al 2017) and corresponding decrease in CDO 2 that persisted even following correction for the independent vasoconstrictor effects of polycythaemia-induced alteration in blood rheology and hypocapnia. The decrease in cerebral perfusion coincided with an impaired ability of the cerebrovasculature to respond to vasodilator stimuli, notably hyperoxia and hypercapnia, the latter being consistently more pronounced in CMS+.…”

Section: Haemodynamic Functionsupporting

confidence: 89%

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Exaggerated systemic oxidative‐inflammatory‐nitrosative stress in chronic mountain sickness is associated with cognitive decline and depression

Bailey

Brugniaux

Filipponi

et al. 2018

The Journal of Physiology

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Key points Chronic mountain sickness (CMS) is a maladaptation syndrome encountered at high altitude (HA) characterised by severe hypoxaemia that carries a higher risk of stroke and migraine and is associated with increased morbidity and mortality. We examined if exaggerated oxidative‐inflammatory‐nitrosative stress (OXINOS) and corresponding decrease in vascular nitric oxide bioavailability in patients with CMS (CMS+) is associated with impaired cerebrovascular function and adverse neurological outcome. Systemic OXINOS was markedly elevated in CMS+ compared to healthy HA (CMS−) and low‐altitude controls. OXINOS was associated with blunted cerebral perfusion and vasoreactivity to hypercapnia, impaired cognition and, in CMS+, symptoms of depression. These findings are the first to suggest that a physiological continuum exists for hypoxaemia‐induced systemic OXINOS in HA dwellers that when excessive is associated with accelerated cognitive decline and depression, helping identify those in need of more specialist neurological assessment and targeted support. Abstract Chronic mountain sickness (CMS) is a maladaptation syndrome encountered at high altitude (HA) characterised by severe hypoxaemia that carries a higher risk of stroke and migraine and is associated with increased morbidity and mortality. The present cross‐sectional study examined to what extent exaggerated systemic oxidative‐inflammatory‐nitrosative stress (OXINOS), defined by an increase in free radical formation and corresponding decrease in vascular nitric oxide (NO) bioavailability, is associated with impaired cerebrovascular function, accelerated cognitive decline and depression in CMS. Venous blood was obtained from healthy male lowlanders (80 m, n = 17), and age‐ and gender‐matched HA dwellers born and bred in La Paz, Bolivia (3600 m) with (CMS+, n = 23) and without (CMS−, n = 14) CMS. We sampled blood for oxidative (electron paramagnetic resonance spectroscopy, HPLC), nitrosative (ozone‐based chemiluminescence) and inflammatory (fluorescence) biomarkers. We employed transcranial Doppler ultrasound to measure cerebral blood flow (CBF) and reactivity. We utilised psychometric tests and validated questionnaires to assess cognition and depression. Highlanders exhibited elevated systemic OXINOS (P < 0.05 vs. lowlanders) that was especially exaggerated in the more hypoxaemic CMS+ patients (P < 0.05 vs. CMS−). OXINOS was associated with blunted cerebral perfusion and vasoreactivity to hypercapnia, impaired cognition and, in CMS+, symptoms of depression. Collectively, these findings are the first to suggest that a physiological continuum exists for hypoxaemia‐induced OXINOS in HA dwellers that when excessive is associated with accelerated cognitive decline and depression, helping identify those in need of specialist neurological assessment and support.

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Section: Discussionsupporting

confidence: 91%

Section: Haemodynamic Functionsupporting

confidence: 89%

Exaggerated systemic oxidative‐inflammatory‐nitrosative stress in chronic mountain sickness is associated with cognitive decline and depression

Bailey

Brugniaux

Filipponi

et al. 2018

The Journal of Physiology

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“…However, there is evidence that even long-term genetic adaptation may vary over extended periods of time. A recent meta-analysis of data from high altitude Andean and Himalayan populations indicates a higher cerebral blood fl ow in Himalayans and a higher hematocrit in Andeans [ 29 ]. Once differences in hematocrit were corrected for, cerebral blood fl ow in Himalayan residents remained higher than their Andean counterparts (~ +20 %).…”

Section: Cerebrovascular Adaptation To Prolonged Exposure To Hypoxiamentioning

confidence: 94%

Influence of Hypoxia on Cerebral Blood Flow Regulation in Humans

Steinback

Poulin

2016

Advances in Experimental Medicine and Biology

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The brain is a vital organ that relies on a constant and adequate supply of blood to match oxygen and glucose delivery with the local metabolic demands of active neurones. It is well established that cerebral blood flow is altered in response to both neural activity and humoral stimuli. Thus, augmented neural activation (e.g. visual stimulation) leads to locally increased cerebral blood flow via functional hyperaemia, whereas humoral stimuli (i.e. alterations in arterial PO2 and PCO2) produce global increases in cerebral blood flow. Perhaps not surprisingly, cerebrovascular responses to neural activity and humoral stimuli may not be highly correlated because they reflect different physiological mechanisms for vasodilation. Exquisite regulation of cerebral blood flow is particularly important under hypoxic conditions when cerebral PO2 can be reduced substantially. Indeed, cerebrovascular reactivity to hypoxia determines the capacity of cerebral vessels to respond and compensate for a reduced oxygen supply. This reactivity is dynamic, changing with prolonged exposure to hypoxic environments, and in patients and healthy individuals exposed to chronic intermittent periods of hypoxia. More recently, a number of animal studies have provided evidence that glial cells (i.e. astrocytes) play an important role in regulating cerebral blood flow under normoxic and hypoxic conditions. This review aims to summarize our current understanding of cerebral blood flow control during hypoxia in humans and put into context the underlying neurovascular mechanisms that may contribute to this regulation.

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“…Additions to that list include evidence of higher nitric oxide levels among Tibetans than among Andean highlanders and the direct association of nitric oxide levels with pulmonary and systemic blood fl ow among Tibetans [ 38 , 44 , 45 ]. Another addition may be higher cerebral blood fl ow among Tibetan than among Andean highlanders [ 46 ]. The addition of lower percent of oxygen saturation of hemoglobin refl ects fi ndings of studies using the same protocol [ 47 , 48 ].…”

Section: A Third Classic Strategy To Detect Naturalmentioning

confidence: 99%

Human Evolution at High Altitude

Beall

2013

High Altitude

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This chapter reviews evidence that natural selection is acting or has acted on indigenous high-altitude populations of the Andean, Tibetan and East African plateaus and resulted in distinctive biological characteristics conferring vigor and health. It describes the results of classic era and genomic era approaches to detecting natural selection. Genomic era evidence of natural selection on high-altitude populations is accumulating rapidly and broadly supports that from the classic era. An important remaining step is to associate phenotypic with genomic variation and to associate them with survival and reproduction, the demographic currency of natural selection.

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Brain Blood Flow in Andean and Himalayan High-Altitude Populations: Evidence of Different Traits for the Same Environmental Constraint

Cited by 27 publications

References 41 publications

Exaggerated systemic oxidative‐inflammatory‐nitrosative stress in chronic mountain sickness is associated with cognitive decline and depression

Exaggerated systemic oxidative‐inflammatory‐nitrosative stress in chronic mountain sickness is associated with cognitive decline and depression

Influence of Hypoxia on Cerebral Blood Flow Regulation in Humans

Human Evolution at High Altitude

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