Role of group I metabotropic glutamate receptors in traumatic spinal cord white matter injury

Sandeep K. Agrawal, Elizabeth Theriault, Michael G. Fehlings

Research output: Contribution to journalArticle

69 Citations (Scopus)

Abstract

Metabotropic glutamate receptors (mGluRs) participate in glutamate neural transmission, but their role in the pathophysiology of spinal cord injury (SCI) has not been explored. Accordingly, we examined the role of group I mGluRs, which are linked to phospholipase C, in mediating SCI using an in vitro model. A dorsal column segment was isolated from the spinal cord of adult rats, maintained in vitro, and injured by compression for 15 sec with a clip having a 2g closing force. Under control conditions after SCI, the compound action potential (CAP) amplitude was reduced to 69.1 ± 5.4% of baseline. Blockade of group I mGluR receptors with MCPG, 4CPG, or AIDA resulted in improved recovery of CAP amplitude (82.2 ± 2.0%, 86.2 ± 3.9%, and 86.0 ± 2.5% of baseline, respectively). The group I/II agonist trans- ACPD and selective group I agonist DHPG exacerbated the posttraumatic reduction of CAP amplitude. The phospholipase C inhibitor U-73122 improved recovery of CAP amplitude after traumatic spinal cord axonal injury. Western blotting and immunocytochemistry demonstrated the presence of mGluR1α- immunopositive astrocytes and the absence of mGluR5 in spinal cord white matter. These studies are consistent with the hypothesis that activation of group I mGluR receptors after SCI exacerbates posttraumatic axonal injury through a phospholipase C dependent mechanism. The presence of mGluR1α labeling on astrocytes suggests a role for these cells in the pathophysiology of SCI. Additional studies in vivo, are required to further clarify the role of mGluRs in acute traumatic SCI.

Original languageEnglish (US)
Pages (from-to)929-941
Number of pages13
JournalJournal of Neurotrauma
Volume15
Issue number11
DOIs
StatePublished - Nov 1998

Fingerprint

Metabotropic Glutamate Receptors
Spinal Cord Injuries
Spinal Cord
Wounds and Injuries
Action Potentials
Type C Phospholipases
Astrocytes
White Matter
Surgical Instruments
Synaptic Transmission
Glutamic Acid
Western Blotting
Immunohistochemistry

Keywords

  • Axons
  • Glia
  • Group I
  • Immunocytochemistry
  • Rat
  • Spinal cord injury
  • mGluR

ASJC Scopus subject areas

  • Clinical Neurology

Cite this

Role of group I metabotropic glutamate receptors in traumatic spinal cord white matter injury. / Agrawal, Sandeep K.; Theriault, Elizabeth; Fehlings, Michael G.

In: Journal of Neurotrauma, Vol. 15, No. 11, 11.1998, p. 929-941.

Research output: Contribution to journalArticle

Agrawal, Sandeep K. ; Theriault, Elizabeth ; Fehlings, Michael G. / Role of group I metabotropic glutamate receptors in traumatic spinal cord white matter injury. In: Journal of Neurotrauma. 1998 ; Vol. 15, No. 11. pp. 929-941.
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