Disease mechanisms which can be modelled with experimental
hypoxia
Symptoms of acute mountain sickness, a disease of the brain which is
developed by individuals who ascent to high altitudes to fast, are often
migraine-like and include headache, nausea and vomiting [83]. An
association between migraine and hypoxia has been suggested for patients
with patent foramen ovale (a hole between the left and right atria of
the heart). In these patients, who also suffer from migraine,
PaO2 was lower than in healthy controls and normobaric
oxygen treatment attenuated the frequency and severity of their
migraines [84]. Furthermore, hypoxia has been shown to act as a
reliable trigger for a complete physiological migraine [85-87].
Frank et al. used normobaric hypoxia at 12.6% oxygen for 6 hours which
triggered migraines in 80% of participants with over 16% presenting
with aura [85]. Schoonman et al. showed that hypoxia was a more
reliable migraine trigger than nitroglycerine, which is the current
experimental standard [87]. Hypoxia also offers a major safety
advantage over the pharmacological models as it can be easily reversed
at any point in the trial, whereas a dose of nitroglycerine cannot be
withdrawn and requires the addition of a second medication like triptans
to terminate its effects [88]. However, this phenomenon is under
investigated as the few existing studies have relatively small
population sizes. Migraine research can greatly benefit from a greater
emphasis on hypoxia, both as a dependable and physiologically accurate
trigger for interventional studies and as a window into the causational
mechanism.
Experimental hypoxia models have been utilized to study various disease
mechanisms associated with migraine. One such mechanism is cortical
spreading depression (CSD), a wave of neuronal depolarization and
subsequent depression that spreads across the cerebral cortex [89].
CSD has been implicated in the generation of migraine aura and is
hypothesized to contribute to the initiation and propagation of migraine
attacks. Hypoxia-induced CSD models have provided insights into the
underlying mechanisms and potential therapeutic targets for migraine
[90]. Furthermore, experimental hypoxia can be used to investigate
the role of oxygen levels in modulating neurovascular function and the
release of neurotransmitters, such as serotonin and CGRP, which are
involved in migraine pathophysiology [91]. Hypoxia models allow
researchers to examine the effects of reduced oxygen levels on cerebral
blood flow, vascular reactivity, and neuroinflammatory processes,
providing valuable information about the interplay between hypoxia and
migraine mechanisms.