Hypoxia-related mechanisms inducing acute mountain sickness and migraine

Abstract

Experimental models of human diseases are vital for pathophysiological and therapeutic research. To investigate the initiation, maintenance, pathophysiology and even termination of a migraine/headache attack these models are urgently needed. Results from different studies promote the profound involvement of hypoxia in migraine and other primary/secondary headaches. The possible mechanisms that drive the induction of headaches through hypoxia are still unknown, but several modes of action, such as increased blood flow, dilation of cerebral arteries, the release of nitroglycerin, calcitonin gene-related peptide and adenosine or increased oxygen extraction are discussed intensively. In studies exposing healthy volunteers and people with a history of migraine to controlled normobaric hypoxia, our research group could demonstrate normobaric hypoxia to be an effective trigger of migraine headaches. Furthermore, a longitudinal measurement of calcitonin gene-related peptide (CGRP), during a hypoxic challenge in migraine patients, revealed increasing CGRP levels with prolonged hypoxic challenge. Since GRP has been linked to migraine and other headache disorders, hypoxia could be regarded as initiator for headaches on a neurotransmitter basis. Furthermore, it has been known for more than 2 decades from studies in vitro and in vivo that hypoxia can induce cortical spreading depression, a phenomenon believed to represent aura. Considering the increased prevalence of migraine in altitude populations and the solid pathophysiological changes on cellular and neurotransmitter level–the role of hypoxia should be investigated in greater detail by the headache community.

Normobaric oxygen may attenuate the headache in patients with patent foramen povale and migraine

“…In patients with migraines and no PFOs there was no abnormal electrical activity detected. Therefore, the presence of slow waves may be a typical characteristic of patients with PFO-migraines in our study [18]. In addition, Hisaki Ozaki et al suggested that hypoxia-induced slowing waves on EEG could be reversed with NBO [26].…”

“…(Fig. 4) [18]. On the basis of these mechanisms, it is reasonable to postulate that migraines and PFO may be associated with hypoxemia in the tissue of the brain.…”

Rapid altitude displacement induce zebrafish appearing acute high altitude illness symptoms

“…Traditionally, animal models such as mice, rats, and pigs have been used in pre-clinical studies to simulate high-altitude conditions in low-pressure chambers [ [11] , [12] , [13] ]. However, these models have limitations, including high costs, ethics for animal manipulation to reduce pain, a maximum of only 20 samples per session, and disruptions in the experimental conditions due to feeding requirements [ 14 , 15 ]. Moreover, these models often lack the capability for systematic behavioral assessments within the chamber and are burdened with long modeling times and waiting cycles.…”

Serum metabolomics of hyperbilirubinemia and hyperuricemia in the Tibetan plateau has unique characteristics

“…Moreover, when people from the plains rapidly enter a plateau, acute mountain sickness (AMS) is likely to occur due to hypoxia. A series of nonspecific clinical syndromes, such as headache, dizziness, nausea, vomiting, insomnia, and fatigue, may occur in mild cases, while in severe cases, AMS will cause damage to the heart, lung, brain, and other important organs 2 – 5 . Furthermore, high altitude exposure could decrease splanchnic perfusion 6 and blood oxygen levels, leading to hypoxia and hypoxia-induced reductive oxidative stress 7 .…”