Group I metabotropic glutamate antagonist reduces acute neuronal degeneration and behavioral deficits after traumatic brain injury in rats.
Recent studies indicate that acute activation of Group I mGluRs following traumatic brain injury (TBI) contributes to the ensuing pathophysiology. The present study examined the effects of post-TBI administration of the selective mGluR1 antagonist (RS)-1-aminoindan-1,5-dicarboxylic acid (AIDA) on acute neuronal degeneration in the hippocampus and long-term sensorimotor and learning/memory outcome. In Experiment 1, 26 rats received 0.4, 2.0, or 10.0 nmol AIDA or artificial CSF vehicle infusion into the hippocampus starting 5 min postinjury. At 24 h after TBI characteristic pyramidal cell degeneration was observed in Fluoro-Jade-stained coronal sections of the CA2/3 sectors of the dorsal hippocampus. The mean (+/-SEM) number of Fluoro-Jade-positive neurons in the 10 nmol AIDA group (184 +/- 32) was significantly less (P < 0.05) than the vehicle group (310 +/- 47). In Experiment 2, 20 rats were trained on sensorimotor and memory tasks prior to parasagittal fluid percussion TBI. Rats were administered 10 nmol AIDA or vehicle as in Experiment 1. Rats were assessed on beam walking and radial arm maze (RAM) performance weekly for 6 weeks after TBI. Acquisition of a Morris water maze (MWM) task was assessed on days 11-15 after TBI. The AIDA-treated group had significantly reduced deficits in beam walk, MWM, and RAM performance compared to the vehicle-treated group. These data indicate that injury-induced acute activation of mGluR1 receptors contributes to both the cellular pathology and the behavioral morbidity associated with TBI.
Lyeth
B G
BG
Department of Neurological Surgery, University of California at Davis, Davis, California, 95616, USA.
Gong
Q Z
QZ
Shields
S
S
Muizelaar
J P
JP
Berman
R F
RF
D000818:Animals; D001522:Behavior, Animal / Q000187:drug effects; D001930:Brain Injuries / Q000188:drug therapy* / Q000473:pathology; D002452:Cell Count; D004195:Disease Models, Animal; D018691:Excitatory Amino Acid Antagonists / Q000008:administration & dosage*; D006624:Hippocampus / Q000187:drug effects / Q000473:pathology; D007189:Indans / Q000008:administration & dosage*; D008297:Male; D018782:Maze Learning / Q000187:drug effects; D008845:Microinjections; D009043:Motor Activity / Q000187:drug effects; D009474:Neurons / Q000187:drug effects* / Q000473:pathology; D017966:Pyramidal Cells / Q000187:drug effects / Q000473:pathology; D051381:Rats; D017207:Rats, Sprague-Dawley; D018094:Receptors, Metabotropic Glutamate / Q000037:antagonists & inhibitors*; D014949:Wounds, Nonpenetrating
C095756:1-aminoindan-1,5-dicarboxylic acid; D018691:Excitatory Amino Acid Antagonists; D007189:Indans; D018094:Receptors, Metabotropic Glutamate; C104077:metabotropic glutamate receptor type 1