Early overuse and disuse of the affected forelimb after moderately severe intraluminal suture occlusion of the middle cerebral artery in rats

We have previously shown that early forced overuse of the affected forelimb worsens outcome following moderately severe transient focal cortical ische mic stroke in rats using a distal middle cerebral artery occlusion (MCAo) m odel. This effect may be site-dependent, because we have also found that ea rly forced use of the affected limb after unilateral 6-OHDA induced degener ation of ascending nigrostriatal dopamine neurons markedly enhanced functio nal outcome and is neuroprotective. The present study examines the effects of early overuse and disuse following a moderately severe proximal MCAo mod el, by means of intraluminal suture occlusion. Ischemia was produced in mal e Long-Evans rats with 60 min of occlusion, or sham surgery was performed. Early overuse or disuse of the affected forelimb was forced by immobilizing either the ipsilateral or contralateral forelimb, respectively, in a plast er cast or the animal was left uncasted. Casts were removed on day 10 and s ensorimotor testing was performed weekly during days 17-38. Animals were sa crificed on day 45 and brains were fixed for later cresyl violet staining. The MCAo + contralateral cast group performed worse than all other groups o n tests of forelimb sensorimotor function. All MCAo groups regardless of ca st condition had significant atrophy of the ischemic striatum, but there wa s no significant atrophy of the ischermic cortex in any group. Forced disus e, but not overuse, of the affected forelimb immediately following proximal ischemia using the intraluminal suture model has detrimental effects on fu nctional outcome, without exaggerating anatomical damage. The effects of di suse and overuse during the first 10 days after stroke differ depending on cortical or subcortical involvement. (C) 2001 Elsevier Science B.V. All rig hts reserved.