Mitochondrial dysfunction in neonatal brain injury

Neonatal hypoxic-ischaemia at term results in life-long consequences for those infants severely affected. The gold standard treatment, therapeutic hypothermia, provides proof-of-concept that post-injury intervention can be effective. However hypothermia is not universally successful and there is an urgent need for synergistic therapies. Mitochondrial dysfunction lies at the centre of the development of neonatal brain injury following hypoxic-ischaemic insult. Not only is mitochondrial dysfunction key in triggering apoptotic cell death but in vivo studies of hypoxic-ischaemia in rodents and in vitro oxygen/glucose deprivation have identified perturbations in mitochondrial dynamics affecting fission, fusion and mitophagy. In particular, the integrity of the mitochondrial fusion protein, Optic Atrophy (OPA)1 appears significantly vulnerable to such insult. Our current research focusses on mechanisms underlying impaired mitochondrial fission and fusion in order to develop strategies for maintaining mitochondrial function, ultimately providing additional neuroprotection for infants following birth asphyxia, where therapeutic hypothermia alone is inadequate.