Hypoxia-ischemia causes abnormalities in glutamate transporters and death of astroglia and neurons in newborn striatum

Ann Neurol. 1997 Sep;42(3):335-48. doi: 10.1002/ana.410420310.


The neonatal striatum degenerates after hypoxia-ischemia (H-I). We tested the hypothesis that damage to astrocytes and loss of glutamate transporters accompany striatal neurodegeneration after H-I. Newborn piglets were subjected to 30 minutes of hypoxia (arterial O2 saturation, 30%) and then 7 minutes of airway occlusion (O2 saturation, 5%), producing cardiac arrest, followed by cardiopulmonary resuscitation. Piglets recovered for 24, 48, or 96 hours. At 24 hours, 66% of putaminal neurons were injured, without differing significantly thereafter, but neuronal densities were reduced progressively (21-44%). By DNA nick-end labeling, the number of dying putaminal cells per square millimeter was increased maximally at 24 to 48 hours. Glial fibrillary acidic protein-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 astrocytes proliferated. By immunocytochemistry, glutamate transporter 1 (GLT1) was lost after ischemia in the astroglial compartment but gained in cells appearing as neurons, whereas neuronal excitatory amino acid carrier 1 (EAAC1) dissipated. By immunoblotting, GLT1 and EAAC1 levels were 85% and 45% of control, respectively, at 24 hours of recovery. Thus, astroglial and neuronal injury occurs rapidly in H-I newborn striatum, with early gliodegeneration and glutamate transporter abnormalities possibly contributing to neurodegeneration.

Publication types

  • Comparative Study
  • Research Support, U.S. Gov't, P.H.S.

MeSH terms

  • ATP-Binding Cassette Transporters / metabolism*
  • Amino Acid Transport System X-AG
  • Animals
  • Animals, Newborn
  • Astrocytes / metabolism
  • Astrocytes / pathology*
  • Biological Transport
  • Brain Ischemia / complications*
  • Brain Ischemia / pathology
  • Carrier Proteins / metabolism*
  • Cell Death
  • Cell Movement
  • Corpus Striatum* / pathology
  • Excitatory Amino Acids / metabolism
  • Glutamate Plasma Membrane Transport Proteins
  • Glutamic Acid / metabolism*
  • Hypoxia / complications*
  • Hypoxia / pathology
  • Neurons / pathology*
  • Putamen / pathology
  • Swine
  • Symporters*


  • ATP-Binding Cassette Transporters
  • Amino Acid Transport System X-AG
  • Carrier Proteins
  • Excitatory Amino Acids
  • Glutamate Plasma Membrane Transport Proteins
  • Symporters
  • Glutamic Acid