Human Brain Blood Flow and Metabolism During Isocapnic Hyperoxia: The Role of Reactive Oxygen Species

Key points

It is unknown whether excessive reactive oxygen species (ROS) production drives the isocapnic hyperoxia (IH)‐induced decline in human cerebral blood flow (CBF) via reduced nitric oxide (NO) bioavailability and leads to disruption of the blood‐brain barrier (BBB) or neural‐parenchymal damage. We then simultaneously quantified CBF, metabolic rate for oxygen (CMRO₂) and transcerebral exchanges of NO‐end products, oxidant, antioxidant, and neural‐parenchymal damage markers under IH with intravenous saline and vitamin C infusion. CBF and CMRO₂ were reduced during IH, responses that were followed by increased oxidative stress and reduced NO bioavailability when saline was infused. No indication of neural‐parenchymal damage or disruption of the BBB was observed during IH. Antioxidant defences were increased during vitamin C infusion, while CBF, CMRO_2, oxidant, and NO bioavailability markers remained unchanged. ROS play a role in the regulation of CBF and metabolism during IH without evidence of BBB disruption or neural‐parenchymal damage.

Abstract

To test the hypothesis that isocapnic hyperoxia (IH) affects cerebral blood flow (CBF) and metabolism through exaggerated reactive oxygen species (ROS) production, reduced nitric oxide (NO) bioavailability, disturbances in the blood‐brain barrier (BBB), and neural‐parenchymal homeostasis, 10 men (24 ± 1yrs.) were exposed to a 10‐min IH trial (100%O₂) while receiving intravenous saline and vitamin C (VC, ascorbic acid (AA), 3 g) infusion. Internal carotid (ICABF), vertebral artery (VABF), and total CBF (tCBF, Doppler ultrasound) were determined. Arterial and right internal jugular venous blood were sampled to quantify the cerebral metabolic rate of oxygen (CMRO₂), transcerebral exchanges (TCE) of NO end‐products (plasma nitrite), antioxidants (AA and AA plus dehydroascorbic acid (AAPDA)) and oxidant biomarkers (thiobarbituric acid‐reactive substances (TBARS) and 8‐isoprostane), and an index of BBB disruption and neuronal‐parenchymal damage (neuron‐specific enolase (NSE)). IH reduced ICABF, tCBF, CMRO₂ while VABF remained unchanged. Arterial 8‐isoprostane and nitrite TCE increased, indicating that CBF decline was related to ROS production and reduced NO bioavailability. AA, AADPA and NSE TCE did not change during IH. VC infusion did not change the resting hemodynamic and metabolic parameters but raised antioxidant defences, as indicated by increased AA/AAPDA concentrations. Negative AAPDA TCE, unchanged nitrite, reductions in arterial, venous 8‐isoprostane, and TBARS TCE indicated that VC infusion effectively inhibited ROS production and preserved NO bioavailability. Similarly, VC infusion prevented IH‐induced decline in regional and total CBF and re‐established CMRO₂. These findings indicate that ROS play a role in CBF regulation and metabolism during IH without evidence of BBB disruption or neural‐parenchymal damage.

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