Apoptotic cell death occurs in the nervous system during normal and in pathological situations. The PI's preliminary data indicate that apoptosis has a major role in the ES cell graft after transplant into the injured rodent spinal cord. The extent of cell death underlie this process are currently unknown. The goal of this proposal is to apoptotic cell death of ES cell-derived neural lineage cells (ESNLCs). In relevant stages of development. In the second, he will characterize the apoptosis-inducing activity of the syrinx fluid which accumulates in the spinal apoptosis-inducing activity, and determine the changes in this activity as a function of time post-injury. Third, he will utilize the paradigms developed in to the molecular mechanisms of apoptosis and to develop cell clines that are resistant to apoptosis. These experiments should help to define the optimal molecules that are responsible for apoptosis induction seen after the success of ESNLC transplants.

Agency
National Institute of Health (NIH)
Institute
National Institute of Neurological Disorders and Stroke (NINDS)
Type
Research Program Projects (P01)
Project #
1P01NS039577-01
Application #
6326690
Study Section
National Institute of Neurological Disorders and Stroke Initial Review Group (NSD)
Project Start
1999-12-17
Project End
2004-11-30
Budget Start
Budget End
Support Year
1
Fiscal Year
2000
Total Cost
$175,259
Indirect Cost
Name
Washington University
Department
Type
DUNS #
062761671
City
Saint Louis
State
MO
Country
United States
Zip Code
63130
Vadivelu, Sudhakar; Stewart, Todd J; Qu, Yun et al. (2015) NG2+ progenitors derived from embryonic stem cells penetrate glial scar and promote axonal outgrowth into white matter after spinal cord injury. Stem Cells Transl Med 4:401-11
Becker, Daniel; Gary, Devin S; Rosenzweig, Ephron S et al. (2010) Functional electrical stimulation helps replenish progenitor cells in the injured spinal cord of adult rats. Exp Neurol 222:211-8
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
Dilmanian, F Avraham; Qu, Yun; Feinendegen, Ludwig E et al. (2007) Tissue-sparing effect of x-ray microplanar beams particularly in the CNS: is a bystander effect involved? Exp Hematol 35:69-77
Huettner, James E; Lu, Aiwu; Qu, Yun et al. (2006) Gap junctions and connexon hemichannels in human embryonic stem cells. Stem Cells 24:1654-67
Vadivelu, Sudhakar; Platik, Marina M; Choi, Luke et al. (2005) Multi-germ layer lineage central nervous system repair: nerve and vascular cell generation by embryonic stem cells transplanted in the injured brain. J Neurosurg 103:124-35
Vadivelu, Sudhakar; Becker, Daniel; McDonald, John W (2005) Generating chimeric spinal cord: a novel model for transplantable oligodendrocyte progenitors derived from embryonic stem cells. Neurosurg Focus 19:E3
Wei, Ling; Cui, Lin; Snider, B Joy et al. (2005) Transplantation of embryonic stem cells overexpressing Bcl-2 promotes functional recovery after transient cerebral ischemia. Neurobiol Dis 19:183-93
Xian, Hai-Qing; Werth, Kelly; Gottlieb, David I (2005) Promoter analysis in ES cell-derived neural cells. Biochem Biophys Res Commun 327:155-62
Lee, Chul-Sang; Tee, Lee Y; Dusenbery, Susan et al. (2005) Neurotrophin and GDNF family ligands promote survival and alter excitotoxic vulnerability of neurons derived from murine embryonic stem cells. Exp Neurol 191:65-76

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