Perinatal hypoxic ischemic encephalopathy (HIE)

HIE in the near-term and term newborn due to perinatal asphyxia is a neurological syndrome that evolves after acute CNS hypoxia/ischemia (HI) during the period of reperfusion/reoxygenation over many hours. In addition to acute impaired materno-placental or placento-fetal blood flow intra partum, chronic or intermittent acute impaired energy and oxygen supply during the antenatal period is an important risk factor. Clinical scores, several biochemical markers (CK-BB, NSE, S-100), neuroimaging and neurophysiological modalities are discussed as diagnostic/prognostic markers within the first days of life that is of clinical interest for intensive care management and future neuroprotective options.

The principal mechanisms leading to neuronal death after HI/reperfusion failure are initiated by energy depletion, activation of excitotoxicity as well inflammatory mechanisms extending the process of secondary neuronal damage (necrosis-apoptosis-continuum) in selectively vulnerable CNS regions.

The most important regulator of adaptation to hypoxia at the molecular level is transcription factor hypoxia-inducible factor-1 (HIF-1) mediating up-regulation of specific target genes, such as EPO, VEGF, GLUT-1, adrenomedullin, involved in the maintenance of oxygen and energy homeostasis. In the brain, the O2-sensitive HIF-1-subunit, HIF-1α, and HIF-1α regulated genes are activated under focal and global HI. Differences in HIF-1α expression between adult and neonatal brain in several animal experiments show the particular role of these endogenous neuroprotective mechanisms in the neonatal brain. Based on own studies, the up-regulation of HIF-1α regulated genes in human placenta and leucocytes of newborns with severe HIE is suggested as additional marker of clinically relevant severe tissue hypoxia in vivo.