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

J. Lee Martin, Ansgar M. Brambrink, Christoph Lehmann, Carlos Portera-Cailliau, Raymond Koehler, Jeffrey Rothstein, Richard J. Traystman

Research output: Contribution to journalArticlepeer-review

223 Scopus citations

Abstract

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 glio-degeneration and glutamate transporter abnormalities possibly contributing to neurodegeneration.

Original languageEnglish (US)
Pages (from-to)335-348
Number of pages14
JournalAnnals of Neurology
Volume42
Issue number3
DOIs
StatePublished - Sep 1997

ASJC Scopus subject areas

  • Neurology
  • Clinical Neurology

Fingerprint Dive into the research topics of 'Hypoxia-ischemia causes abnormalities in glutamate transporters and death of astroglia and neurons in newborn striatum'. Together they form a unique fingerprint.

Cite this