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

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

Research output: Contribution to journalArticle

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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
Externally publishedYes

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Amino Acid Transport System X-AG
Astrocytes
Ischemia
Neurons
Excitatory Amino Acids
Corpus Striatum
Single-Stranded DNA Breaks
Glial Fibrillary Acidic Protein
Cardiopulmonary Resuscitation
Heart Arrest
Immunoblotting
Cell Count
Immunohistochemistry
Hypoxia
DNA
Wounds and Injuries

ASJC Scopus subject areas

  • Neuroscience(all)

Cite this

Lee Martin, J., Brambrink, A., Lehmann, C., Portera-Cailliau, C., Koehler, R., Rothstein, J., & Traystman, R. J. (1997). Hypoxia-ischemia causes abnormalities in glutamate transporters and death of astroglia and neurons in newborn striatum. Annals of Neurology, 42(3), 335-348. https://doi.org/10.1002/ana.410420310

Hypoxia-ischemia causes abnormalities in glutamate transporters and death of astroglia and neurons in newborn striatum. / Lee Martin, J.; Brambrink, Ansgar; Lehmann, Christoph; Portera-Cailliau, Carlos; Koehler, Raymond; Rothstein, Jeffrey; Traystman, Richard J.

In: Annals of Neurology, Vol. 42, No. 3, 09.1997, p. 335-348.

Research output: Contribution to journalArticle

Lee Martin, J, Brambrink, A, Lehmann, C, Portera-Cailliau, C, Koehler, R, Rothstein, J & Traystman, RJ 1997, 'Hypoxia-ischemia causes abnormalities in glutamate transporters and death of astroglia and neurons in newborn striatum', Annals of Neurology, vol. 42, no. 3, pp. 335-348. https://doi.org/10.1002/ana.410420310
Lee Martin J, Brambrink A, Lehmann C, Portera-Cailliau C, Koehler R, Rothstein J et al. Hypoxia-ischemia causes abnormalities in glutamate transporters and death of astroglia and neurons in newborn striatum. Annals of Neurology. 1997 Sep;42(3):335-348. https://doi.org/10.1002/ana.410420310
Lee Martin, J. ; Brambrink, Ansgar ; Lehmann, Christoph ; Portera-Cailliau, Carlos ; Koehler, Raymond ; Rothstein, Jeffrey ; Traystman, Richard J. / Hypoxia-ischemia causes abnormalities in glutamate transporters and death of astroglia and neurons in newborn striatum. In: Annals of Neurology. 1997 ; Vol. 42, No. 3. pp. 335-348.
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