HYPOXIA-ISCHEMIA CAUSES ABNORMALITIES IN GLUTAMATE TRANSPORTERS AND DEATH OF ASTROGLIA AND NEURONS IN NEWBORN STRIATUM

The neonatal striatum degenerates after hypoxia-ischemia (H-I). We tes ted the hypothesis that damage to astrocytes and loss of glutamate tra nsporters accompany striatal neurodegeneration after H-I. Newborn pigl ets were subjected to 30 minutes of hypoxia (arterial O-2 , saturation , 30%) and then 7 minutes of airway occlusion (O-2 , saturation, 5%), producing cardiac arrest, followed by cardiopulmonary resuscitation. P iglets recovered for 24, 48, or 96 hours. At 24 hours, 66% of putamina l neurons were injured, without differing significantly thereafter, bu t neuronal densities were reduced progressively (21-44%). By DNA nick- end labeling, the number of dying putaminal cells per square millimete r was increased maximally at 24 to 48 hours. Glial fibrillary acidic p rotein-positive cell body densities were reduced 48 to 55% at 24 to 48 hours but then recovered by 96 hours. Early postischemia, subsets of astrocytes had fragmented DNA; later postischemia, subsets of astrocyt es proliferated. By immunocytochemistry, glutamate transporter I (GLT1 ) was lost after ischemia in the astroglial compartment but gained in cells appearing as neurons, whereas neuronal excitatory amino acid car rier 1 (EAAC1) dissipated. By immunoblotting, GLT1 and EAAC1 levels we re 85% and 45% of control, respectively, at 24 hours of recovery. Thus , astroglial and neuronal injury occurs rapidly in H-I newborn striatu m, with early glio-degeneration and glutamate transporter abnormalitie s possibly contributing to neurodegeneration.