Hypoxic-ischemic injury of the perinatal brain and neuronal rescue

Exposure to perinatal asphyxia remains a significant cause of death and lon g-term neurological disability. Studies of asphyxia have demonstrated that the development of hypotension and consequent hypotension during ring asphy xia, i.e. hypoxia-ischemia, plays a central role in localising and precipit ating neural injury. Functional models of hypoxia-ischemia have therefore b een used to characterise the events surrounding asphyxial injury. The semin al observation from both clinical and experimental studies is that brain ce lls may initially, recover from the primary hypoxic-ischemic event, only to die many hours, or even days later (secondary or delayed cell death). We h ave found that the evolution of hypoxic-ischemic injury is associated with the characteristic induction over time of a number of broadly anti-apoptoti c growth factors including insulin like growth factor 1 (IGF-1). Secondary cell death appears to be due to the induction of 'apoptosis'-like events in volving a pre-programmed cell death cascade; thus growth factor induction m ay help limit the development of cell death. Consistent with this hypothesi s, exogenous therapy with IGF-1 and similar agents within a few hours of in jury has been shown to be neuroprotective. It is likely, that clinically ef fective rescue therapies in the future will require the development of a mu lti-modal approach, which includes anti-apoptotic agents such as IGF-1.