Oxidative stress and apoptosis after acute respiratory hypoxia and reoxygenation in rat brain

Abstract

Acute hypoxia increases the formation of reactive oxygen species (ROS) in the brain. However, the effect of reoxygenation, unavoidable to achieve full recovery of the hypoxic organ, has not been clearly established. The aim of the present study was to evaluate the effects of exposition to acute severe respiratory hypoxia followed by reoxygenation on the evolution of oxidative stress and apoptosis in the brain. We investigated the effect of in vivo acute severe normobaric hypoxia (rats exposed to 7% O2 for 6 h) and reoxygenation in normoxia (21% O2 for 24 h or 48 h) on oxidative stress markers, the antioxidant system and apoptosis in the brain. After respiratory hypoxia we found increased levels of HIF-1α expression, lipid peroxidation, protein oxidation and nitric oxide in brain extracts. Antioxidant defence systems such as superoxide dismutase (SOD), reduced glutathione (GSH) and glutathione peroxidase (GPx) and the reduced/oxidized glutathione (GSH/GSSG) ratio were significantly decreased in the brain. After 24 h of reoxygenation, oxidative stress parameters and the anti-oxidant system returned to control values. Regarding the apoptosis parameters, acute hypoxia increased cytochrome c, AIF and caspase 3 activity in the brain. The apoptotic effect is greatest after 24 h of reoxygenation. Immunohistochemistry suggests that CA3 and dentate gyrus in the hippocampus seem more susceptible to hypoxia than the cortex. Severe acute hypoxia increases oxidative damage, which in turn could activate apoptotic mechanisms. Our work is the first to demonstrate that after 24 h of reoxygenation oxidative stress is attenuated, while apoptosis is maintained mainly in the hippocampus, which may, in fact, be the cause of impaired brain function.

Extremely low frequency electromagnetic field reduces oxidative stress during the rehabilitation of post-acute stroke patients

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Ubiquinol treatment for TBI in male rats: Effects on mitochondrial integrity, injury severity, and neurometabolism

“…Mitochondria have numerous cellular functions including adenosine triphosphate (ATP) production, ROS production and sequestration, and control of apoptotic pathways (Flippo & Strack, 2017). Damage to the mitochondria can cause an imbalance in these processes resulting in decreased cellular energy production, increased ROS production, and apoptosis (Coimbra-Costa, Alva, Duran, Carbonell, & Rama, 2017;Fischer et al, 2016). Mitochondrial damage also impairs the cellular antioxidant system leading to oxidative stress.…”

Early‐life N‐arachidonoyl‐dopamine exposure increases antioxidant capacity of the brain tissues and reduces functional deficits after neonatal hypoxia in rats

“…An unchanged glutathione content 4 days after hypoxia may suggest the recovery of cellular redox status. In the recent study of Coimbra‐Costa et al, it was shown that the oxidative damage induced by severe hypoxia in adult rats (7% O 2 , 6 h) is reversed 24 h of reoxygenation and the antioxidant activity and components of GSH antioxidant system returned to basal values at 24–48 h of reoxygenation, while the apoptotic events maintained at the 48 h post hypoxia (Coimbra‐Costa et al, 2017).…”

“…Cellular hypoxia and generation of ROS lead to accumulation of HIF1‐α and its translocation to the nucleus, but when the oxygen restores to normal level, HIF1‐α undergoes hydroxylation and proteasomal degradation (Dunwoodie, 2009; Perez‐Lobos et al, 2017). As the HIF1‐α is a marker of tissue hypoxia, increased HIF1‐α mRNA expression indicates the hypoxic status of an organism (Coimbra‐Costa et al, 2017; Coveñas et al, 2014). The elevated expression of HIF1‐α in hypoxic neonatal rats was previously shown in different experimental conditions.…”