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Cognitive impairment caused by hypoxia: from clinical evidences to molecular mechanisms

Abstract

Hypoxia is a state of reduced oxygen supply and excessive oxygen consumption. According to the duration of hypoxic period, it can be classified as acute and chronic hypoxia. Both acute and chronic hypoxia could induce abundant neurological deficits. Although there have been significant advances in the pathophysiological injuries, few studies have focused on the cognitive dysfunction. In this review, we focused on the clinical evidences and molecular mechanisms of cognitive impairment under acute and chronic hypoxia. Hypoxia can impair several cognitive domains such as attention, learning and memory, procession speed and executive function, which are similar in acute and chronic hypoxia. The severity of cognitive deficit correlates with the duration and degree of hypoxia. Recovery can be achieved after acute hypoxia, while sequelae or even dementia can be observed after chronic hypoxia, perhaps due to the different molecular mechanisms. Cardiopulmonary compensatory response, glycolysis, oxidative stress, calcium overload, adenosine, mitochondrial disruption, inflammation and excitotoxicity contribute to the molecular mechanisms of cognitive deficit after acute hypoxia. During the chronic stage of hypoxia, different adaptive responses, impaired neurovascular coupling, apoptosis, transcription factors-mediated inflammation, as well as Aβ accumulation and tau phosphorylation account for the neurocognitive deficit. Moreover, brain structural changes with hippocampus and cortex atrophy, ventricle enlargement, senile plaque and neurofibrillary tangle deposition can be observed under chronic hypoxia rather than acute hypoxia.

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Fig. 1

Data availability

The datasets and supporting materials generated and/or analyzed during the current study are available from the corresponding author on reasonable request.

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This work was supported by grants from the National Natural Science Foundation of China (No.82027802 and No.81620108011).

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XYW contributed to the manuscript preparation, LLC contributed to the manuscript editing, XMJ took responsibility for the conceptualization of the work.

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Wang, X., Cui, L. & Ji, X. Cognitive impairment caused by hypoxia: from clinical evidences to molecular mechanisms. Metab Brain Dis (2021). https://doi.org/10.1007/s11011-021-00796-3

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Keywords

  • Hypoxia
  • Acute
  • Chronic
  • Cognition
  • Clinical evidence
  • Molecular mechanism