SPECIAL SEMINAR – CELLULAR NEUROSCIENCE

For more information contact: zoltan.molnar@dpag.ox.ac.uk

Neonatal hypoxic-ischemic encephalopathy (HIE) is a relatively infrequent event (0,1- 0,2 %) in developed countries, however responsible for 1 M deaths and additional 1 M injured infants around the world. It may occur prior to, during, or after the delivery following a period of decreased placental and/or foetal blood flow. Infants typically are depressed following birth and need resuscitation, suffer multi-organ failure, furthermore, clinical signs of encephalopathy develop early in the first hours and last for long term in severe cases. Morphologically two main patterns of HIE are distinguishable, the predominantly basal ganglia / thalami involvement and the white matter / watershed area injury. Some observations made by histology of placentas of HIE infants suggest that intrauterine origin may play a role in the specific localisation of the injury in the brain. However currently it is not clear what type and extent of a specific insult is responsible for these differences.. During the first days measuring or continuous monitoring the brain electric background activity, neuronal excitation, the disturbed cellular metabolism, variations of brain circulation, inflammatory processes, free radicals involved in the development of HIE now are partly available at the bedside as well. In the future, the growing volume of these detailed clinical observations done during the early days, probably will result in a better understanding of the dynamics and temporal evolution of brain injury. Combining the results of these observations and of longer term follow up studies may help to identify the most significant players among pathophysiologic processes in the development of permanent brain injury. Therapeutic hypothermia (HT) has proved to be efficacious for improving long-term neuro-developmental outcome in neonatal HIE, although the mechanism of neuroprotective effect of HT is not understood well. Following clinical introduction of HT there is still a high burden of mortality and long-term neurological morbidity among survivors. Optimal postnatal intensive care during HT treatment is essential as well. The too fast restoration of the initial extreme deviations of pH, paCO2, paO2 and blood pressure – representing the asphyxial insult – may result in harm. Overshooting to hyperoxia and hypocapnia are common during early resuscitation in the delivery room and NICU, both are suspected to worsen the brain injury in the immature brain. Early start of therapeutic hypothermia can further increase the risk of hypocapnia by reducing metabolic rate and lowering CO2 production. Currently there is no acknowledged additional therapy to increase therapeutic efficacy of HT. The increasing volume of high quality clinical observations may add a significant contribution to the knowledge about normal and pathological human brain development, and inspire basic research as well. DPAG