This project is designed to investigate the effects of intravenous transplantation of bone marrow stromal cells on the rat brain after traumatic brain injury. Traumatic brain injury continues to be an important cause of human morbidity and as many as 50,000 Americans are killed and an equal number are disabled by head trauma each year. Currently, we have no therapeutic intervention to repair the biostructural neuronal damage and treatment consists of evacuating mass lesions and providing an optimal milieu for the brain to recover. In this application, we will transplant marrow stromal cells intravenously in the adult female Wistar rat after head injury with the intention of improving brain function. Adult female Wistar rats will be injured using the controlled cortical impact model of head trauma. After injury, bone marrow stromal cells harvested from the tibia and femur of normal male adult rats will be injected into the tail vein of the female rat. The marrow stromal cells will be identified by Y chromosomes. Following transplantation, the animals will be sacrificed at different time points and brain sections will be stained for immunohistochemistry to examine for proliferation of the marrow stromal cells and the phenotypes of newly generated cells. Using immunohistochemistry and enzyme-linked immunosorbent assay (ELISA), the expression of neurotrophic factors following marrow stromal cell transplantation will also be studied. The safety of marrow stromal cell treatment of traumatic brain injury will be evaluated and a battery of functional outcome measurements will be performed to test for enhanced recovery resulting from treatment. If intravenous transplantation of marrow stromal cells succeeds in improving functional outcome, a new avenue will be opened for further development of therapeutic interventions to improve outcome of traumatic brain injury.

National Institute of Health (NIH)
National Institute of Neurological Disorders and Stroke (NINDS)
Research Project (R01)
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Special Emphasis Panel (ZRG1-BDCN-1 (01))
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Michel, Mary E
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Henry Ford Health System
Schools of Medicine
United States
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Qu, Changsheng; Mahmood, Asim; Liu, Xian Shuang et al. (2011) The treatment of TBI with human marrow stromal cells impregnated into collagen scaffold: functional outcome and gene expression profile. Brain Res 1371:129-39
Xiong, Ye; Mahmood, Asim; Chopp, Michael (2010) Angiogenesis, neurogenesis and brain recovery of function following injury. Curr Opin Investig Drugs 11:298-308
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Qu, Changsheng; Xiong, Ye; Mahmood, Asim et al. (2009) Treatment of traumatic brain injury in mice with bone marrow stromal cell-impregnated collagen scaffolds. J Neurosurg 111:658-65
Xiong, Ye; Qu, Changsheng; Mahmood, Asim et al. (2009) Delayed transplantation of human marrow stromal cell-seeded scaffolds increases transcallosal neural fiber length, angiogenesis, and hippocampal neuronal survival and improves functional outcome after traumatic brain injury in rats. Brain Res 1263:183-91
Xiong, Ye; Mahmood, Asim; Chopp, Michael (2009) Emerging treatments for traumatic brain injury. Expert Opin Emerg Drugs 14:67-84
Qu, Changsheng; Mahmood, Asim; Lu, Dunyue et al. (2008) Treatment of traumatic brain injury in mice with marrow stromal cells. Brain Res 1208:234-9
Mahmood, Asim; Lu, Dunyue; Qu, Changsheng et al. (2007) Treatment of traumatic brain injury in rats with erythropoietin and carbamylated erythropoietin. J Neurosurg 107:392-7
Mahmood, Asim; Lu, Dunyue; Qu, Changsheng et al. (2005) Human marrow stromal cell treatment provides long-lasting benefit after traumatic brain injury in rats. Neurosurgery 57:1026-31; discussion 1026-31

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