Use-dependent exaggeration of brain injury: is glutamate involved?
Extreme overreliance on the impaired forelimb following unilateral lesions of the forelimb representation area of the rat sensorimotor cortex (FL-SMC) leads to exaggeration of the initial cortical injury. Glutamate has repeatedly been implicated in the secondary processes leading to neuronal death following traumatic insult, chiefly because of the neuroprotective properties of excitatory amino acid antagonists in a variety of animal models of brain injury. The present study investigated the possibility that NMDA receptor-mediated processes are involved in use-dependent exaggeration of neuronal injury. Rats were fitted with one-sleeved casts that immobilized the intact forelimb for the first 7 days following FL-SMC lesion, a procedure previously shown to result in use-dependent exaggeration of injury and more severe and persistent limb-use deficits. In the present investigation, administration of MK-801 (1 mg/kg ip once daily on alternate days) during the casting period spared neural tissue surrounding the lesion and enhanced functional recovery of the impaired forelimb. These results suggest a role for NMDA receptor-mediated processes in use-dependent exaggeration of injury.
Humm
J L
JL
Department of Psychology & Institute for Neuroscience, University of Texas at Austin, Austin, Texas, 78712, USA. humm@mail.utexas.edu
Kozlowski
D A
DA
Bland
S T
ST
James
D C
DC
Schallert
T
T
D000704:Analysis of Variance; D000818:Animals; D001930:Brain Injuries / Q000473:pathology / Q000503:physiopathology*; D016291:Dizocilpine Maleate / Q000494:pharmacology*; D005552:Forelimb / Q000294:innervation*; D007839:Functional Laterality; D018698:Glutamic Acid / Q000502:physiology*; D008297:Male; D017551:Microdialysis; D009043:Motor Activity / Q000187:drug effects / Q000502:physiology*; D051381:Rats; D020318:Rats, Long-Evans; D016194:Receptors, N-Methyl-D-Aspartate / Q000502:physiology*; D013003:Somatosensory Cortex / Q000187:drug effects / Q000473:pathology / Q000503:physiopathology*; D013997:Time Factors
D016194:Receptors, N-Methyl-D-Aspartate; D018698:Glutamic Acid; D016291:Dizocilpine Maleate