Reorganization of Remote Cortical Regions After Ischemic Brain Injury: A Potential Substrate for Stroke Recovery

Abstract

Although recent neurological research has shed light on the brain's mechanisms of self-repair after stroke, the role that intact tissue plays in recovery is still obscure. To explore these mechanisms further, we used microelectrode stimulation techniques to examine functional remodeling in cerebral cortex after an ischemic infarct in the hand representation of primary motor cortex in five adult squirrel monkeys. Hand preference and the motor skill of both hands were assessed periodically on a pellet retrieval task for 3 mo postinfarct. Initial postinfarct motor impairment of the contralateral hand was evident in each animal, followed by a gradual improvement in performance over 1-3 mo. Intracortical microstimulation mapping at 12 wk after infarct revealed substantial enlargements of the hand representation in a remote cortical area, the ventral premotor cortex. Increases ranged from 7.2 to 53.8% relative to the preinfarct ventral premotor hand area, with a mean increase of 36.0 +/- 20.8%. This enlargement was proportional to the amount of hand representation destroyed in primary motor cortex. That is, greater sparing of the M1 hand area resulted in less expansion of the ventral premotor cortex hand area. These results suggest that neurophysiologic reorganization of remote cortical areas occurs in response to cortical injury and that the greater the damage to reciprocal intracortical pathways, the greater the plasticity in intact areas. Reorganization in intact tissue may provide a neural substrate for adaptive motor behavior and play a critical role in postinjury recovery of function.

Thinning, movement, and volume loss of residual cortical tissue occurs after stroke in the adult rat as identified by histological and magnetic resonance imaging analysis

“…Other work using electrophysiological techniques also finds that peri-infarct tissue moves relative to the infarct location. (Eysel and Schweigart, 1999;Frost et al, 2003;Jenkins and Merzenich, 1987;Reinecke et al, 2003;Schiene et al, 1999;Zepeda et al, 2004).…”

“…Indeed, intracortical microstimulation and fMRI studies have found that electrophysiological maps can reorganize after cortical stroke in order to compensate for the functional loss in the stroke infarct. Better behavioural outcome is also correlated with the extent of cortical map reorganization (Castro-Alamancos and Borrel, 1995;Friel et al, 2000;Frost et al, 2003;Gharbawie et al, 2005;Kleim et al, 2003;. This cortical reorganization may be mediated by two mechanisms.…”

“…In addition, it has been suggested that the compensatory improvements in skilled behavior that occur in the chronic period may be associated with long-lasting plastic changes in residual tissue including changes in neuronal structure, cortical organization, neurotrophic factor regulation, and electrophysiological responsiveness (Eysel and Schweigart, 1999;Schiene et al, 1999;Frost et al, 2003;Gonzalez and Kolb, 2003;Reinecke et al, 2003;Fridman et al, 2004;Zepeda et al, 2004).…”

“…Dynamic changes observed in peri-infarct tissue have been suggested to mediate post-stroke functional recovery (Fridman et al, 2004;Frost et al, 2003;Gharbawie et al 2007;Liu and Rouiller, 1999;Schallert et al, 2000;Whishaw, 2000). Peri-infarct changes include thinning, volume loss, and density loss in histological tissue (Karl et al, 2010), as well as time-dependent normalization of T2 and fractional diffusion anisotropy (van der Zijden et al, 2008b) as identified by magnetic resonance imaging (MRI).…”

Efficient non-viral transfection of adult neural stem/progenitor cells, without affecting viability, proliferation or differentiation

“…This region neighbouring the cortical infarct likely represents an active brain region involved in post-stroke plasticity with suggested positive effects on functional improvement 158,159 .…”