Gender-dependent changes in physical development, BDNF content and GSH redox system in a model of acute neonatal hypoxia in rats

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

“…In our previous work on the same ANH model, we have shown an increase in HIF1-α and GPx4 mRNA levels in rat brains immediately after hypoxic exposure (Sukhanova et al, 2018). In the current study we have shown that increased HIF1-α and GPx4 mRNA levels persisted for 1.5 h after hypoxia termination, and the GPx2 mRNA expression was also increased at this time point.…”

“…The hypoxic pups had delayed performance in both the righting reflex at P6 and the negative geotaxis test at P12, but not in the gait reflex at P10. In our previous work we have also shown an impairment on these tasks (Sukhanova et al, 2018), which is an evidence of good reproducibility of hypoxia model used. Despite of unchanged glutathione level in 1.5 h and 4 days after ANH, the presence of adverse long‐term outcomes points on the fact that hypoxia has triggered pathological processes within CNS.…”

“…Certainly, as the oxygen supply to the brain is a function of the intensity and duration of the hypoxia, the dynamic changes of glutathione content within brain will depend on the exposure protocol, brain structure and time point of samples collection. In our previous work there was a significant decrease in GSH/GSSG ratio in rat blood immediately after hypoxia, which reflects the presence of oxidative stress associated with ANH (Sukhanova et al, 2018). Based on the present data, we can assume that in our model of ANH the GSH content remained on basal level since we were using the whole brain samples and only 1.5 h have passed from hypoxic exposure, which may be insufficient for the shift in glutathione system in brain tissues.…”

“…In the HI model, HIF1‐α mRNA level was increased immediately after hypoxic exposure and during 24 h of reoxygenation (Bergeron et al, 2000; Li et al, 2014; Sheldon et al, 2009). The hypoxia without ischemia also induced HIF1‐α upregulation immediately after hypoxic episode (Anju and Paulose, 2011; Bergeron et al, 2000; Sheldon et al, 2009; Sukhanova et al, 2018). Our results demonstrated a significant increase of HIF1‐α gene expression during reoxygenation period in hypoxia‐only model.…”

“…Separate determinations of GSSG and GSH + GSSG (total GSH) concentrations as well as total GSH and GSSG measurements and GSH/ GSSG calculations were conducted according to Giustarini with minor modifications (Giustarini et al, 2013). The brain samples preparation were thoroughly described in the previous study (Sukhanova et al, 2018). The total GSH and GSSG measurements were conducted by spectrophotometric recycling assay with 5,5′-dithiobis-(2-nitrobenzoic acid) (DTNB, Thermo Scientific, USA), according to Giustarini (Giustarini et al, 2013).…”