Hypothermic Neuroprotection in Neonatal Inflammatory-Sensitised Hypoxic-Ischaemic Brain Injury

Abstract

Birth asphyxia can lead to hypoxic-ischaemic (HI) brain injury. A concomitant perinatal infection increases the risk of neurological sequelae. Hypothermia treatment (HT) is current standard treatment for birth asphyxia. 40-50% of patients still end up with permanent brain injury. In low-resource settings with high infection rates HT after birth asphyxia did not improve outcome. A neonatal rat model with lipopolysaccharide (LPS)-induced inflammation prior to HI injury negated HT effect. It has been hypothesised that infection prior to HI interfere with the neuroprotective potential of HT. However, infection demographics vary across the world, and LPS only represents gram-negative infections. In our part of the world >90% of term neonatal infections are caused by gram-positive bacteria. We modelled a gram-positive infection prior to an HI insult in a neonatal rat model. Their brains were more vulnerable, and HI brain injury was significantly increased. Still, HT was highly neuroprotective and reduced injury by 80%. This supports that HT should still be offered routinely to asphyxiated infants, at least in high-income countries where gram-negative infections are relatively rare.