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 repeat edly been implicated in the secondary processes leading to neuronal death f ollowing traumatic insult, chiefly because of the neuroprotective propertie s of excitatory amino acid antagonists in a variety of animal models of bra in injury. The present study investigated the possibility that NMDA recepto r-mediated processes are involved in use-dependent exaggeration of neuronal injury. Rats were fitted with one-sleeved casts that immobilized the intac t forelimb for the first 7 days following FL-SMC lesion, a procedure previo usly shown to result in use-dependent exaggeration of injury and more sever e and persistent limb-use deficits. In the present investigation, administr ation of MK-801 (1 mg/kg ip once daily on alternate days) during the castin g period spared neural tissue surrounding the lesion and enhanced functiona l recovery of the impaired forelimb. These results suggest a role for NMDA receptor-mediated processes in use-dependent exaggeration of injury. (C) 19 99 Academic Press.