Hypoxic Preconditioning Increases Brain Glycogen and Delays Energy Depletion from Hypoxia-Ischemia in the Immature Rat

Abstract

Recent studies have shown a protection from cerebral hypoxic-ischemic (HI) brain damage in the immature rat following a prior systemic hypoxic exposure when compared with those not exposed previously. To investigate the mechanism(s) of hypoxic preconditioning, brain glycogen and high-energy phosphate reserves were measured in naïve and preconditioned rat pups subjected to HI. Groups in this study included untouched (naïve) controls, preconditioned controls (i.e., hypoxia only), preconditioned with HI insult, and naïve pups with HI insult. Hypoxic preconditioning was achieved in postnatal-day-6 rats subjected to 8% systemic hypoxia for 2.5 h at 37°C. Twenty-four hours later, they were subjected to unilateral common carotid artery ligation and systemic hypoxia with 8% oxygen at 37°C for 90 min. Animals were allowed to recover from HI for up to 24 h. At specific intervals, animals in each group were frozen in liquid nitrogen for determination of cerebral metabolites. Preconditioned animals showed a significant increase in brain glycogen 24 h following the initial hypoxic exposure, corresponding to the beginning of the HI insult. Measurement at the end of 90 min of HI showed a depletion of high-energy phosphates, ATP and phosphocreatine, in all animals although ATP remained significantly higher in the preconditioned animals. Thus, the energy from increased glycogen following preconditioning slowed high-energy phosphate depletion during HI, thereby allowing for long-term protection.