Cortical tissue loss and major structural reorganization as result of distal middle cerebral artery occlusion in the chronic phase of nude mice

The stroke model of distal middle cerebral artery occlusion is considered a reliable stroke model with high reproducibility and low mortality rate. Thus, it is preferred for assessments of therapeutic strategies, in particular for neurorepair and regeneration studies. However, present literature has reported only on the lesion behavior and behavioral deficits during the acute and subacute phase of maximally three weeks. We have here aimed to characterize the lesion expansion and consequent, potential tissue displacements using structural magnetic resonance imaging modalities, histology, and behavioral tests, during the chronic time window of 12 weeks following stroke induction. We found a severe cortical thinning resulting in 15% tissue loss of the ipsilateral cortex by 6 weeks. After two weeks, massive hippocampus displacement was found, into the cortical tissue void and, in this process, pushing the corpus callosum to the brain surface showing an almost radial direction towards the surface. These massive chronic morphological changes and rearrangements, not known from other stroke models, have relevant consequences for decision of stem cell graft placement for cerebral regeneration to assure persistent graft vitality during a longitudinal investigation in the chronic phase.