There is an evolving understanding that neuronal cortical connections can be altered and remodeled following injury to the central nervous system. Humans with stroke frequently show recovery of function that seems to be correlated with activation of regions both in the peri-infarct zone as well as in the hemisphere opposite to the stroke. Cerebral ischemic injury in animals is accompanied by hyperexcitability in tissue surrounding the ischemic core and frequently in homologous regions of the contralateral cortex. There is clinical and behavioral data showing that the degree of recovery can be altered using sensory augmentation including enriched environments and task-specific training. Recovery following chronic stroke can also be improved with pharmacological treatment, with the recovery dependent on activity during treatment. We will use hemodynamic image mapping to examine the reorganization of the brain following a focal cerebral ischemic insult and correlate this reorganization with behavioral recovery. Focal ischemia/reperfusion will be achieved using a compression model that results in ischemic damage confined to the posteriomedial barrel subfield of the first somatosensory cortex of the rat, and reorganization will be evaluated by examining the changes in the blood flow response maps to vibrissae stimulation. The mystacial vibrissae of the rat, with their corresponding representation in the somatosensory cortex, provides an ideal vehicle for studies dealing with damage and subsequent recovery in the central nervous system. Examination of how the brain reorganizes following ischemia/reperfusion to the rat barrel somatosensory cortex, as opposed to ablative injury, will provide valuable information about strategies for improving recovery following stroke. Strategies for altering reorganization of blood flow and metabolism that will be examined include administration of pharmacological agents and stromal cell, as well as targeted sensory augmentation.

Agency
National Institute of Health (NIH)
Institute
National Institute of Neurological Disorders and Stroke (NINDS)
Type
Research Project (R01)
Project #
2R01NS033785-07
Application #
6542561
Study Section
Special Emphasis Panel (ZRG1-BDCN-3 (01))
Program Officer
Michel, Mary E
Project Start
1995-08-15
Project End
2006-07-31
Budget Start
2002-09-01
Budget End
2003-07-31
Support Year
7
Fiscal Year
2002
Total Cost
$292,960
Indirect Cost
Name
University of Pennsylvania
Department
Neurology
Type
Schools of Medicine
DUNS #
042250712
City
Philadelphia
State
PA
Country
United States
Zip Code
19104
Luckl, Janos; Keating, Jeffrey; Greenberg, Joel H (2008) Alpha-chloralose is a suitable anesthetic for chronic focal cerebral ischemia studies in the rat: a comparative study. Brain Res 1191:157-67
Zhou, Chao; Shimazu, Tomokazu; Durduran, Turgut et al. (2008) Acute functional recovery of cerebral blood flow after forebrain ischemia in rat. J Cereb Blood Flow Metab 28:1275-84
Burnett, Mark G; Shimazu, Tomokazu; Szabados, Tamas et al. (2006) Electrical forepaw stimulation during reversible forebrain ischemia decreases infarct volume. Stroke 37:1327-31
Shimazu, Tomokazu; Inoue, Ikuo; Araki, Nobuo et al. (2005) A peroxisome proliferator-activated receptor-gamma agonist reduces infarct size in transient but not in permanent ischemia. Stroke 36:353-9
Burnett, Mark G; Detre, John A; Greenberg, Joel H (2005) Activation-flow coupling during graded cerebral ischemia. Brain Res 1047:112-8
Durduran, Turgut; Burnett, Mark G; Yu, Guoqiang et al. (2004) Spatiotemporal quantification of cerebral blood flow during functional activation in rat somatosensory cortex using laser-speckle flowmetry. J Cereb Blood Flow Metab 24:518-25
Durduran, Turgut; Yu, Guoqiang; Burnett, Mark G et al. (2004) Diffuse optical measurement of blood flow, blood oxygenation, and metabolism in a human brain during sensorimotor cortex activation. Opt Lett 29:1766-8
Culver, Joseph P; Durduran, Turgut; Furuya, Daisuke et al. (2003) Diffuse optical tomography of cerebral blood flow, oxygenation, and metabolism in rat during focal ischemia. J Cereb Blood Flow Metab 23:911-24
Yu, Guoqiang; Durduran, Turgut; Furuya, Daisuke et al. (2003) Frequency-domain multiplexing system for in vivo diffuse light measurements of rapid cerebral hemodynamics. Appl Opt 42:2931-9
Hoffman, John R; Greenberg, Joel H; Furuya, Daisuke et al. (2003) Rats recovering from unilateral barrel-cortex ischemia are capable of completing a whisker-dependent task using only their affected whiskers. Brain Res 965:91-9

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