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.

National Institute of Health (NIH)
National Institute of Neurological Disorders and Stroke (NINDS)
Research Project (R01)
Project #
Application #
Study Section
Special Emphasis Panel (ZRG1-BDCN-3 (01))
Program Officer
Jacobs, Tom P
Project Start
Project End
Budget Start
Budget End
Support Year
Fiscal Year
Total Cost
Indirect Cost
Washington University
Schools of Medicine
Saint Louis
United States
Zip Code
Mohamad, Osama; Chen, Dongdong; Zhang, Lingling et al. (2011) Erythropoietin reduces neuronal cell death and hyperalgesia induced by peripheral inflammatory pain in neonatal rats. Mol Pain 7:51
Hu, Xinyang; Wei, Ling; Taylor, Tammi M et al. (2011) Hypoxic preconditioning enhances bone marrow mesenchymal stem cell migration via Kv2.1 channel and FAK activation. Am J Physiol Cell Physiol 301:C362-72
Francis, K R; Wei, L (2010) Human embryonic stem cell neural differentiation and enhanced cell survival promoted by hypoxic preconditioning. Cell Death Dis 1:e22
Zeng, Xiang Jun; Yu, Shan Ping; Zhang, Like et al. (2010) Neuroprotective effect of the endogenous neural peptide apelin in cultured mouse cortical neurons. Exp Cell Res 316:1773-83
Li, Ying; Yu, Shan Ping; Mohamad, Osama et al. (2010) Sublethal transient global ischemia stimulates migration of neuroblasts and neurogenesis in mice. Transl Stroke Res 1:184-96
Li, Wen-Lei; Yu, Shan Ping; Ogle, Molly E et al. (2008) Enhanced neurogenesis and cell migration following focal ischemia and peripheral stimulation in mice. Dev Neurobiol 68:1474-86
Hu, Xinyang; Yu, Shan Ping; Fraser, Jamie L et al. (2008) Transplantation of hypoxia-preconditioned mesenchymal stem cells improves infarcted heart function via enhanced survival of implanted cells and angiogenesis. J Thorac Cardiovasc Surg 135:799-808
Theus, Michelle Hedrick; Wei, Ling; Cui, Lin et al. (2008) In vitro hypoxic preconditioning of embryonic stem cells as a strategy of promoting cell survival and functional benefits after transplantation into the ischemic rat brain. Exp Neurol 210:656-70
Li, Jimei; Lu, Zhongyang; Li, Wen-Lei et al. (2008) Cell death and proliferation in NF-kappaB p50 knockout mouse after cerebral ischemia. Brain Res 1230:281-9
Cui, Lin; Jiang, Jun; Wei, Ling et al. (2008) Transplantation of embryonic stem cells improves nerve repair and functional recovery after severe sciatic nerve axotomy in rats. Stem Cells 26:1356-65

Showing the most recent 10 out of 27 publications