The neuroprotective actions of hypoxic preconditioning and postconditioning in a neonatal rat model of hypoxic–ischemic brain injury

Abstract

Perinatal hypoxic–ischemic (HI) brain injury remains a major contributing factor to newborn mortality and morbidity. Preconditioning with mild hypoxia has been shown to protect the brain against HI insults and it has recently been shown that mild hypoxia administered after a brain injury, termed ‘postconditioning’ can protect the adult mouse brain. Here, we have investigated the neuroprotective effects of hypoxic pre- and postconditioning in a neonatal rat model of HI brain injury. 7-Day-old Sprague–Dawley rat pups underwent unilateral common carotid artery ligation in combination with 3h at 5.5% oxygen. Hypoxic treatments consisted of either 3h of 8% oxygen performed 24h prior to injury (preconditioning); or 1h of 8% oxygen 24h post-injury, performed once a day for 5 days (postconditioning). Brains were removed 1 week post-injury for histological analysis. HI caused an increase in lesion volume compared to controls and both hypoxic pre- and postconditioning reduced the degree of brain damage following HI injury. To specifically examine neuronal loss, NeuN immunohistochemistry and regional brain area analysis were performed. HI injury caused a loss in NeuN staining in all brain regions examined. Preconditioning with hypoxia resulted in a significant reduction in cortical, hippocampal and striatal neuronal loss, compared with HI alone. Hypoxic postconditioning resulted in a reduction in cortical and striatal neuronal loss, compared to HI alone. Our results further support the clinical potential for mild hypoxia in the treatment of brain injuries, either as a pre- or post-injury treatment strategy.