Role of group I metabotropic glutamate receptors in traumatic spinal cord white matter injury.
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 2 g 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 mGluR1alpha-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 mGluR1alpha 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.
Agrawal
S K
SK
Division of Neurosurgery, University of Toronto, and Toronto Hospital Research Institute, Ontario, Canada.
Theriault
E
E
Fehlings
M G
MG
D000367:Age Factors; D000818:Animals; D001253:Astrocytes / Q000737:chemistry / Q000378:metabolism; D001565:Benzoates / Q000494:pharmacology; D003515:Cycloleucine / Q000031:analogs & derivatives / Q000494:pharmacology; D004594:Electrophysiology; D004963:Estrenes / Q000494:pharmacology; D018691:Excitatory Amino Acid Antagonists / Q000494:pharmacology; D005904:Glial Fibrillary Acidic Protein / Q000032:analysis; D005998:Glycine / Q000031:analogs & derivatives / Q000494:pharmacology; D007150:Immunohistochemistry; D008297:Male; D008564:Membrane Potentials / Q000187:drug effects / Q000502:physiology; D009412:Nerve Fibers / Q000737:chemistry* / Q000187:drug effects / Q000502:physiology*; D018696:Neuroprotective Agents / Q000494:pharmacology; D010726:Phosphodiesterase Inhibitors / Q000494:pharmacology; D011760:Pyrrolidinones / Q000494:pharmacology; D051381:Rats; D017208:Rats, Wistar; D018094:Receptors, Metabotropic Glutamate / Q000032:analysis / Q000037:antagonists & inhibitors / Q000502:physiology*; D012118:Resorcinols / Q000494:pharmacology; D013116:Spinal Cord / Q000737:chemistry / Q000166:cytology; D013119:Spinal Cord Injuries / Q000378:metabolism*; D010738:Type C Phospholipases / Q000037:antagonists & inhibitors
D001565:Benzoates; D004963:Estrenes; D018691:Excitatory Amino Acid Antagonists; D005904:Glial Fibrillary Acidic Protein; D018696:Neuroprotective Agents; D010726:Phosphodiesterase Inhibitors; D011760:Pyrrolidinones; D018094:Receptors, Metabotropic Glutamate; D012118:Resorcinols; C104077:metabotropic glutamate receptor type 1; D003515:Cycloleucine; C036361:1-amino-1,3-dicarboxycyclopentane; C060229:1-(6-((3-methoxyestra-1,3,5(10)-trien-17-yl)amino)hexyl)-1H-pyrrole-2,5-dione; C079694:alpha-methyl-4-carboxyphenylglycine; C079215:3,5-dihydroxyphenylglycine; C079693:4-carboxyphenylglycine; D010738:Type C Phospholipases; D005998:Glycine