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The Journal of Neuroscience, April 11, 2007, 27(15):4101-4109; doi:10.1523/JNEUROSCI.4295-06.2007
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Development/Plasticity/Repair
Extensive Turnover of Dendritic Spines and Vascular Remodeling in Cortical Tissues Recovering from Stroke
Craig E. Brown,1 Ping Li,1 Jamie D. Boyd,2 Kerry R. Delaney,2 andTimothy H. Murphy1 1Department of Psychiatry, Brain Research Center, University of British Columbia, Vancouver, British Columbia, Canada V6T 1Z3, and 2Department of Biology, University of Victoria, Victoria, British Columbia, Canada V8W 3N5
Correspondence should be addressed to Dr. Timothy H. Murphy, 4N1-2255 Wesbrook Mall, University of British Columbia, Vancouver, British Columbia, Canada V6T 1Z3. Email: thmurphy{at}interchange.ubc.ca
Recovery of function after stroke is thought to be dependent on the reorganization of adjacent, surviving areas of the brain. Macroscopic imaging studies (functional magnetic resonance imaging, optical imaging) have shown that peri-infarct regions adopt new functional roles to compensate for damage caused by stroke. To better understand the process by which these regions reorganize, we used in vivo two-photon imaging to examine changes in dendritic and vascular structure in cortical regions recovering from stroke. In adult control mice, dendritic arbors were relatively stable with very low levels of spine turnover (<0.5% turnover over 6 h). After stroke, however, the organization of dendritic arbors in peri-infarct cortex was fundamentally altered with both apical dendrites and blood vessels radiating in parallel from the lesion. On a finer scale, peri-infarct dendrites were exceptionally plastic, manifested by a dramatic increase in the rate of spine formation that was maximal at 1–2 weeks (5–8-fold increase), and still evident 6 weeks after stroke. These changes were selective given that turnover rates were not significantly altered in ipsilateral cortical regions more distant to the lesion (>1.5 mm). These data provide a structural framework for understanding functional and behavioral changes that accompany brain injury and suggest new targets that could be exploited by future therapies to rebuild and rewire neuronal circuits lost to stroke.
Key words: stroke; ischemia; dendrite; spines; angiogenesis; two-photon imaging; photothrombosis; forelimb; cortex; plasticity
Received Oct. 2, 2006; revised March 3, 2007; accepted March 9, 2007.
Correspondence should be addressed to Dr. Timothy H. Murphy, 4N1-2255 Wesbrook Mall, University of British Columbia, Vancouver, British Columbia, Canada V6T 1Z3. Email: thmurphy{at}interchange.ubc.ca
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