A comparison of hyperbaric oxygen versus hypoxic cerebral preconditioning in neonatal rats.

The potency of hyperbaric preconditioning (HBO-PC) is uncertain compared to well-validated ischemic or hypoxic models and no studies have directly compared HBO-PC to hypoxic preconditioning (HPC). We subjected rat pups to unilateral carotid cauterization followed by 90 min (min) of hypoxia using 8% O(2). Three HBO-PC regimes (maximum 2.5 atmospheres for 150 min) were compared to HPC (150 min of 8% O(2)) for changes in mortality and brain weight. Preconditioning-induced oxidative stress was assessed using aconitase activity and manganese superoxide dismutase (MnSOD) transcript levels. Initial brain weight data revealed a large coefficient of variation and compelled an examination of the temperature sensitivity of the model that revealed a narrow optimal range of 35 to 37 degrees C of variability in brain injury and mortality. With rigorous temperature control, high dose HBO-PC and HPC showed comparable anatomic (mean hemispheric weight decrease: control 42%, HPC 25% (P=0.01), HBO-PC 26% (P=0.01) and mortality protection (control 14.7%, HPC 5.9% HBO-PC 5.7%, P=0.001). High dose HBO-PC, but not HPC, suppressed aconitase activity by 65% at 24 h after the preconditioning stimulus (P=0.001). In contrast, MnSOD mRNA increased 2.5-fold at 24 h after HPC (P=0.007) but not after high dose HBO-PC. Thus, when temperature variability is eliminated, HBO-PC and HPC elicit similar preconditioning efficacy in neonatal brain but invoke different defenses against oxidative stress.

Intrathecal administration of a novel apoE-derived therapeutic peptide improves outcome following perinatal hypoxic-ischemic injury.

Perinatal hypoxic-ischemic brain injury remains a significant clinical problem for which there remains no adequate therapeutic intervention. Apolipoprotein E (apoE) is a 299 amino acid protein that has been demonstrated to modify functional recovery following acute ischemic and traumatic brain injury. The aim of the current study was to evaluate whether administration of an apoE-derived peptide could reduce CNS injury in a rodent model of perinatal hypoxia and ischemia. We found that intrathecal delivery of an apoE-mimetic peptide caused a significant reduction in post-ischemic brain necrosis, as reflected by decreased reduction in ipsilateral brain weight 7 days following hypoxic-ischemic injury. These results suggest that administration of an apoE-derived therapeutic peptide represents a novel therapeutic strategy in the clinical setting of perinatal hypoxic-ischemic injury.