Role of Na+-Ca2+ exchanger after traumatic or hypoxic/ischemic injury to spinal cord white matter

Daniel J. Tomes, Sandeep K. Agrawal

Research output: Contribution to journalArticle

31 Scopus citations

Abstract

Background context: Spinal cord injury is a devastating condition in which clinical disability results from demyelination of white matter tracts. Changes in glial-axonal signaling, and enhanced Ca2+ channel activity with excessive accumulation of intracellular Ca2+, is a common phenomenon after hypoxia/ischemia or mechanical trauma to spinal cord dorsal column white matter tracts leading to irreversible injury. Purpose: In the present study we examined the role of Na+-Ca2+ exchanger (NCX) at physiological temperatures after hypoxia/ischemia and compressive injury to spinal cord dorsal column white matter in vitro. Study design: A 30-mm length of dorsal column was isolated from the spinal cord of adult rats, pinned in an in vitro recording chamber (maintained at 37°C) and injured by exposure to a hypoxic atmosphere for 60 minutes or compressed with a modified aneurysm clip (2-gm closing force) for 15 seconds. The functional integrity of the dorsal column was monitored electrophysiologically by quantitatively measuring the compound action potential (CAP) with glass microelectrodes. Results: The mean CAP decreased to 49.5 ± 5.7% and 49.4 ± 2.6% of control (p<.05) after hypoxia/ischemia and compressive injury, respectively. KB-R7943, a potent, selective NCX reverse mode inhibitor, significantly promoted greater recovery of CAP amplitude to 82.0 ± 10.0% and 70.8 ± 10.7% of control (p<.05) after hypoxic/ischemic or compressive injury to dorsal column white matter, respectively, when applied at 10 μM concentration. Bepridil (Research Biochemical Inc., Natick, MA, USA) (a less selective NCX inhibitor), when applied at 10 μM and 50 μM concentration promoted CAP amplitude recovery only to 46.8 ± 7.8% and 29.9 ± 3.3% of control, respectively, after hypoxic/ ischemic injury to dorsal column white matter. Western blot analysis identified NCX presence with positive immunolabeling of 160 kD and 120 kD NCX proteins in the spinal cord white matter. Conclusion: In conclusion, at physiological temperature NCX activation plays an important role in intracellular calcium overload after hypoxic/ischemic and compressive injury to spinal cord dorsal column white matter in vitro.

Original languageEnglish (US)
Pages (from-to)35-40
Number of pages6
JournalSpine Journal
Volume2
Issue number1
DOIs
StatePublished - Jan 2 2002

Keywords

  • Axons
  • Dorsal column
  • Rat, Na-Ca exchanger
  • Spinal cord injury

ASJC Scopus subject areas

  • Surgery
  • Orthopedics and Sports Medicine
  • Clinical Neurology

Fingerprint Dive into the research topics of 'Role of Na<sup>+</sup>-Ca<sup>2+</sup> exchanger after traumatic or hypoxic/ischemic injury to spinal cord white matter'. Together they form a unique fingerprint.

  • Cite this