Intraventricular infusion of N-methyl-D-aspartate - 2. Acute neuronal consequences

W. Dalton Dietrich, M. Halley, O. Alonso, M. Y T Globus, R. Busto

Research output: Contribution to journalArticle

30 Citations (Scopus)

Abstract

This study documents the ultrastructural features of acute neuronal injury following N-methyl-d-aspartate (NMDA) receptor activation. NMDA (100 nmol/μl) or vehicle was infused over a 15-min period into the lateral ventricle of adult rats. After perfusion fixation, specimens demonstrating normal and abnormal patterns of vascular permeability to horserdish peroxidase were sampled for ultrastructural analysis. In NMDA-infused rats, brain regions exhibiting protein extravasation contained swollen dendritic profiles and abnormal neuronal perikarya. Although periventricular regions were most severely affected, parenchymal abnormalities were also detected in the cerebral cortex, septum, striatum, thalamus, hypothalamus and cerebellum. Mildly affected dendrites contained dark compact mitochondria, while in severely swollen dendrites mitochrondia were enlarged with ruptured cristae. Focal sites of plasma membrane disruption were also detected within swollen dendrites. Swollen neurons commonly displayed peripheral pallor and increased numbers of cytoplasmic vacuoles. Other neurons appeared dark and shrunken, some containing disrupted mitochrondria and pyknotic nuclei. Pretreatment with the NMDA antagonist MK-801 (2 mg/kg) attenuated the neuronal and dendritic alterations. In conditions where cerebrospinal fluid levels of glutamate are abnormally elevated, excessive NMDA receptor activation may lead to early vascular and neuronal complications which could work in concert to promote brain injury.

Original languageEnglish
Pages (from-to)630-637
Number of pages8
JournalActa Neuropathologica
Volume84
Issue number6
DOIs
StatePublished - Nov 1 1992

Fingerprint

Intraventricular Infusions
N-Methylaspartate
Dendrites
Aspartic Acid
Pallor
Neurons
Dizocilpine Maleate
Lateral Ventricles
Capillary Permeability
Vacuoles
Thalamus
Cerebral Cortex
Brain Injuries
Cerebellum
Peroxidase
Hypothalamus
Blood Vessels
Cerebrospinal Fluid
Glutamic Acid
Mitochondria

Keywords

  • Dentrites
  • Electron microscopy
  • Excitotoxicity
  • Glutamate
  • N-Methyl-d-aspartate

ASJC Scopus subject areas

  • Neuroscience(all)
  • Pathology and Forensic Medicine
  • Clinical Neurology

Cite this

Intraventricular infusion of N-methyl-D-aspartate - 2. Acute neuronal consequences. / Dalton Dietrich, W.; Halley, M.; Alonso, O.; Globus, M. Y T; Busto, R.

In: Acta Neuropathologica, Vol. 84, No. 6, 01.11.1992, p. 630-637.

Research output: Contribution to journalArticle

Dalton Dietrich, W. ; Halley, M. ; Alonso, O. ; Globus, M. Y T ; Busto, R. / Intraventricular infusion of N-methyl-D-aspartate - 2. Acute neuronal consequences. In: Acta Neuropathologica. 1992 ; Vol. 84, No. 6. pp. 630-637.
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