In vivo measurements of mitochondrial function and cell death following hypoxic/ischaemic damage to the new-born brain.

Critically impaired gas exchange to the brain due to decreased oxygen (hypoxia) or reduced blood flow (ischaemia) is a major cause of brain injury in the perinatal period. There is an accumulating body of evidence suggesting that the irreversible cellular damage in the neonatal brain that occurs subsequent to an hypoxic/ischaemic insult is at the level of the mitochondria. Much of this evidence has been obtained by novel non-invasive measurements of mitochondrial function in vivo. This review focuses on four techniques: near-infrared spectroscopy, magnetic resonance spectroscopy, magnetic resonance imaging and electron paramagnetic resonance spectroscopy. The advantages and disadvantages of these in vivo methods are described in patients and animal models. The picture that emerges is of a slow (1-2 day) energy failure, occurring at the level of the brain mitochondria and leading to a primarily apoptotic cell death. Moderate post-insult hypothermia prevents this damage by an unknown mechanism. It is stressed that isolated cell studies alone are not sufficient to understand the processes occurring at the biochemical and physiological levels. The use of the non-invasive techniques described to understand the biochemistry occurring in vivo is therefore an invaluable aid in integrating cellular and organismal studies of the role of mitochondria in cell death.