Effects of the AMPA receptor antagonist NBQX on outcome of newborn pigs after asphyxic cardiac arrest

Ansgar Brambrink, J. Lee Martin, Daniel F. Hanley, Kyra J. Becker, Raymond C. Koehler, Richard J. Traystman

Research output: Contribution to journalArticle

28 Citations (Scopus)

Abstract

In neonates, asphyxia is a common cause of neuronal injury and often results in seizures. The authors evaluated whether blockade of α-amino-3- hydroxy-5-methylisoxazole-4-propionic acid (AMPA) receptors during asphyxia and early recovery with 2,3-dihydroxy-6-nitro-7-sulfamoylbenzo-(F)- quinoxaline (NBQX) ameliorates neurologic deficit and histopathology in 1- week-old piglets. Anesthetized piglets were exposed to a sequence of 30 minutes of hypoxia, 5 minutes of room air ventilation. 7 minutes of airway occlusion, and cardiopulmonary resuscitation. Vehicle or NBQX was administered intravenously before asphyxia (30 mg/kg) and during the first 4 hours of recovery (15 mg/kg/h). Neuropathologic findings were evaluated at 96 hours of recovery by light microscopic and cytochrome oxidase histochemical study. Cardiac arrest occurred at 5 to 6 minutes of airway occlusion, and cardiopulmonary resuscitation restored spontaneous circulation independent of treatment modalities in about 2 to 3 minutes. Neurologic deficit over the 96- hour recovery period was not ameliorated by NBQX. Seizure activity began after 24 to 48 hours in 7 of 10 animals with vehicle and in 9 of 10 of animals with NBQX. In each group, four animals died in status epilepticus. Neuropathologic outcomes were not improved by NBQX. The density of remaining viable neurons was decreased in parietal cortex and putamen by NBQX treatment. Metabolic defects in cytochrome oxidase activity were worsened by NBQX treatment. Seizure activity during recovery was associated with reduced neuronal viability in neocortex and striatum in piglets from both groups that survived for 96 hours. This neonatal model of asphyxic cardiac arrest and resuscitation generates neurologic deficits, clinical seizure activity, and selective damage in regions of basal ganglia and sensorimotor cortex. In contrast to other studies in mature brain, AMPA receptor blockade with NBQX failed to protect against neurologic damage in the immature piglet and worsened postasphyxic histopathologic outcome in neocortex and putamen.

Original languageEnglish (US)
Pages (from-to)927-938
Number of pages12
JournalJournal of Cerebral Blood Flow and Metabolism
Volume19
Issue number8
StatePublished - 1999
Externally publishedYes

Fingerprint

Heart Arrest
Swine
Asphyxia
Seizures
Neurologic Manifestations
Putamen
Neocortex
Cardiopulmonary Resuscitation
Electron Transport Complex IV
Quinoxalines
Parietal Lobe
bucide
2,3-dioxo-6-nitro-7-sulfamoylbenzo(f)quinoxaline
propionic acid
Status Epilepticus
Basal Ganglia
Resuscitation
Nervous System
Ventilation
Therapeutics

Keywords

  • AMPA receptors
  • Cerebral ischemia
  • Glutamate
  • Newborn
  • Pig

ASJC Scopus subject areas

  • Endocrinology
  • Neuroscience(all)
  • Endocrinology, Diabetes and Metabolism

Cite this

Brambrink, A., Martin, J. L., Hanley, D. F., Becker, K. J., Koehler, R. C., & Traystman, R. J. (1999). Effects of the AMPA receptor antagonist NBQX on outcome of newborn pigs after asphyxic cardiac arrest. Journal of Cerebral Blood Flow and Metabolism, 19(8), 927-938.

Effects of the AMPA receptor antagonist NBQX on outcome of newborn pigs after asphyxic cardiac arrest. / Brambrink, Ansgar; Martin, J. Lee; Hanley, Daniel F.; Becker, Kyra J.; Koehler, Raymond C.; Traystman, Richard J.

In: Journal of Cerebral Blood Flow and Metabolism, Vol. 19, No. 8, 1999, p. 927-938.

Research output: Contribution to journalArticle

Brambrink, A, Martin, JL, Hanley, DF, Becker, KJ, Koehler, RC & Traystman, RJ 1999, 'Effects of the AMPA receptor antagonist NBQX on outcome of newborn pigs after asphyxic cardiac arrest', Journal of Cerebral Blood Flow and Metabolism, vol. 19, no. 8, pp. 927-938.
Brambrink, Ansgar ; Martin, J. Lee ; Hanley, Daniel F. ; Becker, Kyra J. ; Koehler, Raymond C. ; Traystman, Richard J. / Effects of the AMPA receptor antagonist NBQX on outcome of newborn pigs after asphyxic cardiac arrest. In: Journal of Cerebral Blood Flow and Metabolism. 1999 ; Vol. 19, No. 8. pp. 927-938.
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