The effects of hypoxic preconditioning on white matter damage following hypoxic-ischaemic injury in the neonatal rat brain

Abstract

Myelination is an essential process in human development that is carried out by oligodendrocytes in the central nervous system. Hypoxic-ischaemic (HI) brain injury can disrupt myelination by causing oxidative stress, inflammation and excitotoxicity, resulting in the loss of myelin as well as cells of the oligodendrocyte lineage. We have previously shown that hypoxic preconditioning (HP) can protect against HI injury, however, to date there have been no reports of its effects on white matter injury. Sprague-Dawley rat pups (postnatal day (P) 6) were placed into control and HP groups. On P7, pups were further separated into HI and sham surgery groups. HI pups underwent a unilateral common carotid artery occlusion and then exposed to 8% oxygen for 3h. Sham pups underwent the same procedure without occlusion and were maintained in room air. Brains were removed 5 days post-surgery for analysis. In HI-only pups there was a significant reduction in brain volume observed. Consequently, when HP was performed prior to HI, the loss of brain tissue was prevented. The number of early and late oligodendrocyte progenitors (preOLs) in the corpus callosum was unaffected by HI, however, HI reduced the amount of myelin basic protein, indicating that HI may inhibit the maturation of preOLs. Whilst HP did not affect preOL density, it was found to prevent the loss of myelin caused by HI. This indicates that HP may either protect myelin directly or possibly promote the maturation of preOLs to regenerate the lost or damaged myelin.