Hypoxic injury of isolated axons is independent of ionotropic glutamate receptors

Suzanne M. Underhill, Mark P. Goldberg

Research output: Contribution to journalArticlepeer-review

42 Scopus citations


Axonal injury in white matter is an important consequence of many acute neurological diseases including ischemia. A role for glutamate-mediated excitotoxicity is suggested by observations from in vitro and in situ models that AMPA/kainate blockers can reduce axonal injury. We assessed axonal vulnerability in primary murine neuronal cultures, with axons isolated from their cell bodies using a compartmented chamber design. Transient removal of oxygen and glucose in the axon compartment resulted in irreversible loss of axon length and neurofilament labeling. This injury was not prevented by addition of ionotropic glutamate receptor blockers and could not be reproduced by glutamate receptor agonists. However, hypoxic injury was prevented by blockade of voltage-gated sodium channels, inhibition of calpain and removal of extracellular calcium. These results suggest that isolated, unmyelinated axons are vulnerable to hypoxic injury which is mediated by influx of sodium and calcium but is independent of glutamate receptor activation.

Original languageEnglish (US)
Pages (from-to)284-290
Number of pages7
JournalNeurobiology of Disease
Issue number2
StatePublished - Feb 2007
Externally publishedYes


  • AMPA/kainate
  • Axon
  • Calpain
  • Excitotoxicity
  • Glutamate
  • Ischemia
  • NMDA
  • Oxygen-glucose deprivation
  • White matter

ASJC Scopus subject areas

  • Neurology


Dive into the research topics of 'Hypoxic injury of isolated axons is independent of ionotropic glutamate receptors'. Together they form a unique fingerprint.

Cite this