PRIMARY SENSORY AND FOREBRAIN MOTOR SYSTEMS IN THE NEWBORN BRAIN ARE PREFERENTIALLY DAMAGED BY HYPOXIA-ISCHEMIA

Cerebral hypoxia-ischemia causes encephalopathy and neurologic disabil ities in newborns by unclear mechanisms. We tested the hypothesis that hypoxia-ischemia causes brain damage in newborns that is system-prefe rential and related to regional oxidative metabolism. One-week-old pig lets mere subjected to 30 minutes of hypoxia and then seven minutes of airway occlusion, producing asphyxic cardiac arrest, followed by card iopulmonary resuscitation and four-day recovery. Brain injury in hypox ic-ischemic piglets (n = 6) compared to controls (n = 5) was analyzed by hematoxylin-eosin, Nissl, and silver staining; relationships betwee n regional vulnerability and oxidative metabolism mere evaluated by cy tochrome oxidase histochemistry, Profile counting-based estimates show ed that 13% and 27% of neurons in layers II/III and layers IV/V of som atosensory cortex had ischemic cytopathology, respectively; CA1 neuron al perikarya appeared undamaged, and <10% of CA3 and CA4 neurons mere injured; and neuronal damage was 79% in putamen, 17% in caudate, but n ucleus accumbens was undamaged. Injury was found preferentially in pri mary sensory neocortices (particularly somatosensory cortex!, basal ga nglia !predominantly putamen, subthalamic nucleus, and substantia nigr a reticulate), ventral thalamus, geniculate nuclei, and tectal nuclei. In sham piglets, vulnerable regions generally had higher cytochrome o xidase levels than less vulnerable areas. Postischemic alterations in cytochrome oxidase were regional and laminar, with reductions (31-66%) occurring in vulnerable regions and increases (20%) in less vulnerabl e areas. Sire conclude that neonatal hypoxia-ischemia causes highly or ganized, system-preferential and topographic encephalopathy, targeting regions that function in sensorimotor integration and movement contro l. This distribution of neonatal encephalopathy is dictated possibly b y regional function, mitochondrial activity, and connectivity. (C) 199 7 Wiley-Liss, Inc.