ABSTRACT
Focal ischemia induces long-term pathophysiological consequences in widespread brain areas. Here we analyzed long-term effects of sequential cortical lesions on brain volume and cognitive function. Rats received either single photothrombotic lesions in the forelimb sensorimotor cortex (SL) or two lesions in sequence either immediately (DL0), 2 days (DL2), 7 days (DL7), or 10 days (DL10) after the first surgery in the homotopic contralateral area. Infarct and global brain volume were measured 7 days (SL and DL2 groups) and one month (all groups) after the last period of ischemia. In the weeks following a stroke, the single lesion shrank considerably. This shrinkage was accentuated by a further lesion received either earlier or later. Thirty-one days after obtaining the second lesion, the lesion scars on both sides had a mean volume of 5.8 +/- 2.3 mm3 in DL2 as compared to 8.5 +/- 3.5 mm3 in SL-animals. In addition, there was a super-additive loss of residual brain volume by 2.2-8.0% in each hemisphere in animals with sequential lesions. In the watermaze, this loss of brain volume corresponded to a slight but significant impairment in performance. The present study revealed a complex interaction of lesions in animals with sequential strokes associated with global reduction of brain volume and cognitive impairment indicating degenerative processes beyond the lesions itself.
Subject(s)
Cerebral Infarction/pathology , Cognition/physiology , Intracranial Embolism and Thrombosis/pathology , Time , Animals , Behavior, Animal , Cerebral Infarction/complications , Escape Reaction/physiology , Functional Laterality/physiology , Intracranial Embolism and Thrombosis/etiology , Male , Maze Learning/physiology , Rats , Rats, Wistar , Reaction Time/physiology , Time FactorsABSTRACT
Current evidence indicates reorganization of motor cortex in association with motor behavior. To investigate the molecular basis for these changes rats were fitted with limb-restricting vests which forced the use of one forelimb for 10 days. Using cDNA macroarrays, expression profiles of the corresponding motor cortices connected to the overused and immobilized limbs were analyzed. In the overused motor cortex up-regulations were observed exclusively, including genes coding for voltage-gated ion channels, trafficking and targeting proteins, and intracellular kinase network members (10 genes). In the contralateral immobilized cortex changes were restricted to down-regulation, mainly involving genes pertaining to DNA-binding, translation, neuronal signaling and metabolic pathways (9 genes). At least some of these changes are likely to represent the molecular substrate of use-dependent plasticity.
