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 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.
Martin
L J
LJ
Department of Pathology, Johns Hopkins University School of Medicine, Baltimore, MD 21205-2196, USA.
Brambrink
A M
AM
Lehmann
C
C
Portera-Cailliau
C
C
Koehler
R
R
Rothstein
J
J
Traystman
R J
RJ
D018528:ATP-Binding Cassette Transporters / Q000378:metabolism*; D027322:Amino Acid Transport System X-AG; D000818:Animals; D000831:Animals, Newborn; D001253:Astrocytes / Q000378:metabolism / Q000473:pathology*; D001692:Biological Transport; D002545:Brain Ischemia / Q000150:complications* / Q000473:pathology; D002352:Carrier Proteins / Q000378:metabolism*; D016923:Cell Death; D002465:Cell Movement; D003342:Corpus Striatum / Q000473:pathology; D018846:Excitatory Amino Acids / Q000378:metabolism; D050491:Glutamate Plasma Membrane Transport Proteins; D018698:Glutamic Acid / Q000378:metabolism*; D000860:Hypoxia / Q000150:complications* / Q000473:pathology; D009474:Neurons / Q000473:pathology*; D011699:Putamen / Q000473:pathology; D013552:Swine; D027981:Symporters
D018528:ATP-Binding Cassette Transporters; D027322:Amino Acid Transport System X-AG; D002352:Carrier Proteins; D018846:Excitatory Amino Acids; D050491:Glutamate Plasma Membrane Transport Proteins; D027981:Symporters; D018698:Glutamic Acid