Brain metabolism and extracellular space diffusion parameters during and after transient global hypoxia in the rat cortex

Hypoxia results in both reversible and irreversible changes in the brain extracellular space (ECS). This study utilized microdialysis to monitor changes in the energy-related metabolites lactate, pyruvate, glucose and glutamate in the rat cortex before, during and after 30-min transient global hypoxia, induced in anesthetized rats by reducing inspired oxygen to 6% O2 in nitrogen. Changes in metabolite levels were compared with ECS diffusion parameters calculated from diffusion curves of tetramethylammonium applied by iontophoresis.Significant increases in lactate concentration and the lactate/pyruvate ratio, as well as decreased glucose levels, were found in the cortex immediately after the induction of hypoxia. Following recovery to ventilation with air, extracellular lactate and glucose levels and the lactate/pyruvate ratio returned to control levels within 40, 20 and 30 min, respectively. Glutamate levels started to increase 20–30 min after the onset of hypoxia and returned to prehypoxic values within 30–40 min of reoxygenation. The ECS volume fraction α decreased by about 5% from 0.18 ± 0.01 during the first 20–25 min of hypoxia; after 25 min α dropped a further 22% to 0.14 ± 0.01. Within 10 min of reoxygenation, α returned to control values, then increased to 0.20 ± 0.01 and remained at this level until the end of the experiment. The observed 22% decrease in α markedly influences dialysate levels measured during hypoxia.In our study, the complete posthypoxic recovery of cortical metabolite levels and ECS diffusion properties suggests that metabolic enzymes and related cellular components (e.g., mitochondria) may tolerate prolonged hypoxic periods and recover to prehypoxic values.