A new directly observable model for targeted strokes in adult Wistar rats will be used to test recovery of function in somatosensory cortex through restored microcirculation and neural plasticity. This unique model uses direct mapping of functional neural activity and blood flow as case studies in the same rats by videomicroscopy before, acutely after, and 30 days after ligation of 3-5 local branches of the middle cerebral artery supplying whisker barrel cortex. The hypotheses to be tested are: Growth of arteriolar collaterals is necessary for restoration of blood flow. Angiogenesis produces new intraparenchymal capillaries. Neural responses and neurovascular coupling reappear by 30 days. Activation by single whisker stimulation can occur in novel cortical areas after that whisker's barrel was lost in the infarct. Reorganized or new neuroanatomical projections are correlated with new response areas. Angiogenesis and neural reorganization are interrelated in recovery from stroke. The methods include functional mapping by intrinsic optical signals, evoked potentials, identification and measurements of arteriolar collaterals with time, local arteriovenous transits of fluorescein, BrdU labeling of vascular proliferation, autoradiography for local blood flow and glucose utilization, and mapping small infarcts and neuroanatomical projections by postmortem histology. This rodent model tests mechanisms for recovery of local blood flow and of neural function that bear on human stroke rehabilitation.
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