2 Understanding cerebral energy metabolism: a key to successful neuroprotection

Abstract

Aerobic energy metabolism utilizes glucose and oxygen to produce all the energy needs of the brain. Anaerobically, the brain switches to the significantly less efficient glycolytic pathway for its very basic energy requirements. Anaerobic glycolysis provides the brain with a limited amount of energy and time to maintain ion homoeostasis and other essential processes before several events occur that lead to brain cell damage and death. One of the damaging events has been postulated to be lactic acidosis; the accumulation of lactic acid due to increased glucose utilization via anaerobic glycolysis and the inability of lactic acid to exit the brain owing to the blood-brain barrier impermeability. This chapter questions the validity of the lactic acidosis hypothesis. We offer another hypothesis in its place in which lactate produced in the brain during an ischaemic insult becomes the only utilizable, obligatory substrate for aerobic energy metabolism on return of normoxic conditions. This hypothesis is directly supported by data of recent in vitro studies and indirectly by existing data in numerous in vivo studies; for the most part the data have been ignored and until now have remained unexplained. This new hypothesis may force us to re-examine not only our understanding of cerebral energy metabolism but also our approach to cerebral protection and resuscitation.