Behavioral experience effects on forelimb strength recovery and corticostriatal axonal plasticity after experimental middle cerebral artery occlusion

The overarching goal of this dissertation project is to test how behavioral experiences with the paretic and non-paretic forelimbs influence recovery of paretic forelimb strength and corticostriatal projections after strokes caused by occlusion of the middle cerebral artery. In order to accomplish this goal, we pursued the following specific aims: 1) to establish a model that characterizes paretic forelimb weakness using an automated skilled reaching task after middle cerebral artery occlusion (MCAo) in the rat, 2) to test the effects of skilled rehabilitative strength training on paretic forelimb recovery and corticostriatal axonal plasticity after MCAo, and 3) to test whether training with the non-paretic forelimb interferes with recovery of the paretic forelimb and its effects on axonal plasticity after MCAo. The results from the study assessing the first aim are described in chapter 2. We found that the Isometric Pull Task, an automated skilled reaching task, detects forelimb weakness after experimental MCAo. Furthermore, we found that the intraluminal suture MCAo model consistently produces large infarcts damaging somatosensory cortex and striatum. The results for the second aim are described in chapter 3, where we show that daily rehabilitative training with the paretic forelimb for six weeks on the Isometric Pull Task improves paretic forelimb strength after MCAo. We also found that rehabilitative training reduces contralesional striatal axon projections but does not affect contralesional cortical or ipsilesional striatal axon projections that originate from cortex of the lesioned hemisphere. The results for the third aim are described in chapter 4, where we show that 14 days of non-paretic forelimb training post-MCAo on the Isometric Pull Task does not reduce the efficacy of rehabilitative training. These findings suggest that compensating with the intact body side early after stroke may not always be detrimental to recovery and may depend on infarct locus. We also show that non-paretic limb use after MCAo does not influence corticostriatal axonal plasticity. These findings are consistent with the lack of behavioral effect of non-paretic limb training. We finish in chapter 5 by summarizing the results and discussing the implications and potential future direction of this work.