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PMID: 11125001 Published · ppublish English Journal Article Research Support, Non-U.S. Gov't Research Support, U.S. Gov't, P.H.S.

NBQX attenuates excitotoxic injury in developing white matter.

The Journal of neuroscience : the official journal of the Society for Neuroscience ·Vol. 20 ·No. 24 ·2000-12-15 ·Pages 9235-41

Follett PL, Rosenberg PA, Volpe JJ, Jensen FE

Abstract

The excitatory neurotransmitter glutamate is released from axons and glia under hypoxic/ischemic conditions. In vitro, oligodendrocytes (OLs) express non-NMDA glutamate receptors (GluRs) and are susceptible to GluR-mediated excitotoxicity. We evaluated the role of GluR-mediated OL excitotoxicity in hypoxic/ischemic white matter injury in the developing brain. Hypoxic/ischemic white matter injury is thought to mediate periventricular leukomalacia, an age-dependent white matter lesion seen in preterm infants and a common antecedent to cerebral palsy. Hypoxia/ischemia in rat pups at postnatal day 7 (P7) produced selective white matter lesions and OL death. Furthermore, OLs in pericallosal white matter express non-NMDA GluRs at P7. Unilateral carotid ligation in combination with hypoxia (6% O(2) for 1 hr) resulted in selective, subcortical white matter injury with a marked ipsilateral decrease in immature and myelin basic protein-expressing OLs that was also significantly attenuated by 6-nitro-7-sulfamoylbenzo(f)quinoxaline-2,3-dione (NBQX). Intracerebral AMPA demonstrated greater susceptibility to OL injury at P7 than in younger or older pups, and this was attenuated by systemic pretreatment with the AMPA antagonist NBQX. These results indicate a parallel, maturation-dependent susceptibility of immature OLs to AMPA and hypoxia/ischemia. The protective efficacy of NBQX suggests a role for glutamate receptor-mediated excitotoxic OL injury in immature white matter in vivo.

MeSH Terms
Aging/metabolism Animals Excitatory Amino Acid Agonists/administration & dosage Excitatory Amino Acid Antagonists/administration & dosage Glutamic Acid/metabolism,toxicity Hypoxia-Ischemia, Brain/drug therapy,metabolism,pathology Injections, Intraperitoneal Male Microinjections Nerve Fibers, Myelinated/drug effects,metabolism,pathology Neuroprotective Agents/administration & dosage Oligodendroglia/drug effects,immunology,metabolism,pathology Quinoxalines/administration & dosage Rats Rats, Long-Evans Receptors, AMPA/metabolism Receptors, Glutamate/metabolism alpha-Amino-3-hydroxy-5-methyl-4-isoxazolepropionic Acid/administration & dosage
Chemicals
Excitatory Amino Acid Agonists Excitatory Amino Acid Antagonists Neuroprotective Agents Quinoxalines Receptors, AMPA Receptors, Glutamate 2,3-dioxo-6-nitro-7-sulfamoylbenzo(f)quinoxaline Glutamic Acid alpha-Amino-3-hydroxy-5-methyl-4-isoxazolepropionic Acid
Authors & Affiliations
4 authors, click to expand affiliations / ORCID
Follett P L
Department of Neurology and Program in Neuroscience, Children's Hospital and Harvard Medical School, Boston, Massachusetts 02115, USA.
Rosenberg P A
Volpe J J
Jensen F E
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Article Info
Journal
The Journal of neuroscience : the official journal of the Society for Neuroscience
Abbr.
J Neurosci
ISSN
1529-2401
Published
2000-12-15
Pages
9235-41
Language
English
Region
United States
NLM ID
8102140
PMCID
PMC6773002
Subset
IM
Grants
NINDS NIH HHS · NS 38475 · United States
NINDS NIH HHS · P01 NS038475 · United States
NINDS NIH HHS · R56 NS031718 · United States
NICHD NIH HHS · K08 HD001359 · United States
NICHD NIH HHS · HD 18655 · United States
NINDS NIH HHS · NS 31718 · United States
NICHD NIH HHS · P30 HD018655 · United States
NINDS NIH HHS · R01 NS031718 · United States
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