Cerebral Hypoperfusion and Metabolic Regulation during Isocapnic Hyperoxia: The Role of Reactive Oxygen Species

Abstract

IntroductionHyperoxia provokes cerebral hypoperfusion but its impact on regional cerebrovascular responses and brain metabolism remains unclear. While a paradoxical hypocapnia explains cerebral hypoperfusion, the reduction in cerebral blood flow (CBF) observed during isocapnic hyperoxia may be related to the exaggerated generation of reactive oxygen species (ROS) that in turn might induce transient disruption of the blood‐brain barrier (BBB) and neuronal‐parenchymal damage.AimTo determine the impact of isocapnic hyperoxia on regional cerebrovascular responses and brain metabolism, as well as the contribution of ROS for IH‐induced cerebral hypoperfusion and neuronal‐parenchymal damage.MethodsTen healthy men (26 ± 1 yrs.) were exposed to normoxia (3 min, NX – 21% O2) and a 10‐min IH trial (100% O2), under saline (SIH) and vitamin C (VCIH – 3 g) intravenous infusion. Internal carotid (ICA), vertebral (VA) artery blood flow (BF, Doppler ultrasound) and total CBF ((ICA BF + VA BF)*2) were determined at the last 30 s of each intervention. Radial artery and right jugular venous blood were sampled to quantify cerebral metabolic rate of O2 (CMRO2), transcerebral exchange (TCE) of antioxidant (total ascorbic acid (TAA), HPLC) and oxidant biomarkers (8‐isoprostane, ELISA) as well as of the neuron‐specific enolase (NES, ELISA), a marker of neuronal‐parenchymal damage.ResultsSIH provoked a reduction in ICA perfusion (Δ −63 ± 15 mL/min vs. NX, p = 0.002) while no significant change was observed in VA BF (Δ −6 ± 4 mL/min vs. NX, p > 0.05). The change in ICA perfusion (ICA vs. VA, p = 0.003) was the main drive to the SIH‐induced decrease in TCBF (Δ −138 ± 32 mL/min vs. NX, p = 0.002) without changing CRMO2 (Δ +2 ± 8 mmol/100 g/min vs. NX, p > 0.05). SHI increased arterial 8‐isoprostane levels (Δ +33 ± 31 pg/mL vs. NX, p = 0.012) and evoked a shift from a net cerebral output to an uptake (TCE NX −33 ± 86 vs. TCE SHI 153 ± 80, p = 0.038). While SIH reduced jugular venous TAA (Δ −73 ± 21 μM vs. NX, p = 0.007), no changes on arterial levels and TCE were observed (p > 0.05). Arterial, jugular venous and TCE of NES did not change during SIH (vs. NX, p > 0.05). In contrast, vitamin C infusion increased arterial (Δ +551 ± 219 μM vs. SIH, p < 0.001) and jugular venous (Δ +669 ± 250 μM vs. SIH, p < 0.001) TAA, which prevented IH‐induced reductions in ICA BF (Δ +22 ± 30 mL/min vs. SIH, p < 0.001) and TCBF (Δ +47 ± 95 mL/min vs. SIH, p < 0.001) and provoked an increase in CRMO2 (Δ +25 ± 8 mmol/100 g/min vs. SIH, p = 0.048). Arterial 8‐isoprostane (Δ −27 ± 11 pg/mL vs. SIH, p = 0.009) did not increase during VCIH and no change in TCE was observed. Similarly to SIH, VCIH did not induced changes in NES.ConclusionThese findings indicate that ROS, without any evidence of a maladaptive consequence to BBB or neuronal‐parenchymal damage, play a role in regional and total cerebral perfusion and metabolic regulation during isocapnic hyperoxia.Support or Funding InformationSupport: CNPq, CAPES, FAPERJ, FINEP.This abstract is from the Experimental Biology 2018 Meeting. There is no full text article associated with this abstract published in The FASEB Journal.