Comparative Response of Brain to Chronic Hypoxia and Hyperoxia

Abstract

Two antithetic terms, hypoxia and hyperoxia, i.e., insufficient and excess oxygen availability with respect to needs, are thought to trigger opposite responses in cells and tissues. This review aims at summarizing the molecular and cellular mechanisms underlying hypoxia and hyperoxia in brain and cerebral tissue, a context that may prove to be useful for characterizing not only several clinically relevant aspects, but also aspects related to the evolution of oxygen transport and use by the tissues. While the response to acute hypoxia/hyperoxia presumably recruits only a minor portion of the potentially involved cell machinery, focusing into chronic conditions, instead, enables to take into consideration a wider range of potential responses to oxygen-linked stress, spanning from metabolic to genic. We will examine how various brain subsystems, including energetic metabolism, oxygen sensing, recruitment of pro-survival pathways as protein kinase B (Akt), mitogen-activated protein kinases (MAPK), neurotrophins (BDNF), erythropoietin (Epo) and its receptors (EpoR), neuroglobin (Ngb), nitric oxide (NO), carbon monoxide (CO), deal with chronic hypoxia and hyperoxia to end-up with the final outcomes, oxidative stress and brain damage. A more complex than expected pattern results, which emphasizes the delicate balance between the severity of the stress imposed by hypoxia and hyperoxia and the recruitment of molecular and cellular defense patterns. While for certain functions the expectation that hypoxia and hyperoxia should cause opposite responses is actually met, for others it is not, and both emerge as dangerous treatments.

Oxidative Stress Markers to Investigate the Effects of Hyperoxia in Anesthesia

“…Both hypoxic and hyperoxic conditions generate oxidative stress, although likely with different biochemical mechanisms, and can cause common cellular and systemic damage [1,13]. A better knowledge of the oxidative stress induced by hyperoxia and a rational panel of biomarkers can be useful to optimize the treatment and prevention of hypoxia during surgery.…”

“…On the other hand, O 2 excess constitutes a patho-physiological condition defined as hyperoxia. Our organism responds to hyperoxia by adaptive and/or potentially harmful mechanisms surprisingly similar to the ones involved in the adaptation to hypoxia [1,2].…”

COVID-19-associated cardiovascular morbidity in older adults: a position paper from the Italian Society of Cardiovascular Researches

“…Hyperoxia-induced injury may occur even in patients undergoing laparoscopic surgery breathing mixtures containing 40% to 80% oxygen (Ottolenghi et al 2019). Hyperoxia-driven oxidative stress is expected to alter the expression of genes that regulate pathways underlying different responses to oxidative stress (Terraneo and Samaja 2017). Intuitively, the direction of the alterations driven by hyperoxia is opposite to those elicited by hypoxia.…”

Dysregulation of Neuronal Iron Homeostasis as an Alternative Unifying Effect of Mutations Causing Familial Alzheimer’s Disease

“…In this form, it is unable to bind IRE sequences. Notably, ACO1 may possibly also be converted to IRP1 under conditions of oxidative stress ( Gehring et al, 1999 ), e.g., due to either hypoxia or hyperoxia ( Terraneo and Samaja, 2017 ). Analysis of the subcellular localization of IRP1 shows it to be concentrated in the ER ( Patton et al, 2005 ), which is consistent with the importance in Alzheimer’s disease of the MAM (see later).…”