Insights into ischemia-induced dendritic and vascular plasticity through In vivo imaging

Stroke remains a leading cause of long-term disability in adults, and impairments in the upper extremities are particularly common. Many post-stroke remodeling events are activity dependent and can be influenced by post-ischemic behavioral experience through similar mechanisms as experience-dependent plasticity. The overarching goal of these dissertation studies was to understand how behavioral experience, in the form of rehabilitative training (RT), after ischemia impacts neuronal and vascular structural remodeling. This was tested using a mouse model of ischemia-induced upper-limb impairments in adult transgenic mice containing yellow or green fluorescent protein (YFP/GFP) in a subset of layer V cortical pyramidal neurons. First, I examined the impact of manual skill learning on dendritic spine dynamics in vivo in the trained motor cortex (MC) of intact mice (Chapter 2). We found that spine formation was significantly enhanced after 3 days of training, which was followed by an equal and opposite increase in spine elimination by day 6 and then a return to baseline levels for the remainder of the training duration. New spines formed on day 3 were preferentially stabilized and were correlated with performance gains. Next, I tested whether a variation of the photothrombotic stroke model that confines laser illumination to individual arteries on the cortical surface, could better reproduce aspects of the vascular penumbra, such that it would be better suited for examining how structural remodeling events are influenced by the penumbra. We monitored post-ischemic cerebral blood flow (CBF) at 6, 48, and 120 h following MC infarcts and found that artery-targeted photothrombosis created a wider, more graded penumbra. In addition, it instigated vascular structural remodeling, and caused impairments in skilled-reaching performance in mice. Lastly, I examined the impact of RT on spine dynamics and recovery of skilled reaching performance following photothrombotic infarcts to MC. We found that ischemia instigated widespread increases in spine turnover that persisted for up to 5 weeks. RT increased the stabilization of new spines formed in weeks 2 and 3 after ischemia, which was correlated with improvements in skilled reaching, indicating that new spine maintenance could represent a structural mechanism for the recovery of reaching performance.Neuroscienc