Intermittent hypoxic conditioning restores neurological dysfunction of mice induced by long‐term hypoxia

Abstract

Oxygen (O 2 ) is essential for bodily tissues, and hypoxia usually causes transient or irreversible tissue damage and dysfunction. 1 Environmental hypoxia is common in aerospace activities, deep sea diving, mountain climbing, and plateau travel, and it usually increases the probability of body or organ damage. 2 As the most sensitive organ to hypoxia, the brain undergoes a series of response processes when exposed to hypoxia. 3 Short-term or mild hypoxia triggers hypoxic responses or conditioning mechanisms in the brain,

A2-astrocyte activation by short term hypoxia rescue α-synuclein preformed fibril induced neuronal cell death

“…However, we used primary cells in which genomic and phenotypic stability was well validated. Although we only searched for astrocyte transcripts, other mechanisms, such as inhibiting pro-in ammatory cytokines or oxidative stress, are also possible (Lin et al 2002;Li et al 2023). As our qPCR data indicate we believe the immune response is deeply involved in the adaptive response to hypoxia.…”

The Hypoxia Response Pathway: A Potential Intervention Target in Parkinson's Disease?

“…82 Intermittent hypoxia at an FiO 2 of 0.10 reversed this pro-inflammatory and re-enabled neurogenesis, suggesting postconditioning effects, that is, inducible protection by hypoxia-based interventions after the toxic insult. 82 Through this mechanism, long-term intermittent hypoxia might rescue iron-induced oxidative injury in dopaminergic neurons, 83 a common finding in PD. 84 Similarly, a multiple-week protocol of 15-hour (chronic) hypoxia daily, untypical for hypoxic conditioning, did not ameliorate MPTP/MPP + -induced neurodegeneration, although it still reduced indicators of oxidative stress.…”

“…This coincided with upregulation of the pro‐inflammatory markers interleukin‐1β (IL‐1β), IL‐6 and tumor necrosis factor α, and hippocampal neurodegeneration 82 . Intermittent hypoxia at an FiO 2 of 0.10 reversed this pro‐inflammatory and re‐enabled neurogenesis, suggesting postconditioning effects, that is, inducible protection by hypoxia‐based interventions after the toxic insult 82 . Through this mechanism, long‐term intermittent hypoxia might rescue iron‐induced oxidative injury in dopaminergic neurons, 83 a common finding in PD 84 .…”

“…Differences in effects between hypoxic conditioning and chronic (intermittent) hypoxia are exemplified in a few studies. For example, in mice, sustained hypoxia at a fraction of inspired oxygen (FiO 2 ) of 0.13 up to 3 days did not affect motor behavior and induced hippocampal neurogenesis, but longer‐term exposure negatively affected movement, cognition, and balance 82 . This coincided with upregulation of the pro‐inflammatory markers interleukin‐1β (IL‐1β), IL‐6 and tumor necrosis factor α, and hippocampal neurodegeneration 82 .…”

“…For example, in mice, sustained hypoxia at a fraction of inspired oxygen (FiO 2 ) of 0.13 up to 3 days did not affect motor behavior and induced hippocampal neurogenesis, but longer‐term exposure negatively affected movement, cognition, and balance 82 . This coincided with upregulation of the pro‐inflammatory markers interleukin‐1β (IL‐1β), IL‐6 and tumor necrosis factor α, and hippocampal neurodegeneration 82 . Intermittent hypoxia at an FiO 2 of 0.10 reversed this pro‐inflammatory and re‐enabled neurogenesis, suggesting postconditioning effects, that is, inducible protection by hypoxia‐based interventions after the toxic insult 82 .…”