Abstract

This project is designed to investigate the efficacy of combination treatment of marrow stromal cells (MSCs) and statins (simvastatin) in improving functional outcome after traumatic brain injury (TBI). Our previous studies have shown that MSCs have a beneficial effect after TBI in rats. To augment the therapeutic benefit of MSCs a combination therapy of MSCs with simvastatin has been designed. Female Wistar rats will be injured using the controlled cortical impact model of head trauma. After injury, simvastatin will be administered orally, and MSCs harvested from male adult rats will be injected into the tail vein of the rats. To compare the efficacy of combination treatment (MSC + simvastatin) with MSC and simvastatin monotherapies other group of rats will be administered either MSCs or simvastatin, solely. The functional outcome of rats will be monitored with a battery of tests, and animals will be sacrificed at different time points. Brain sections will be stained with immunohistochemistry and MSCs will be identified by localizing Y chromosomes within them. The induction of brain plasticity with treatment will be measured by studying neurogenesis, synaptogenesis and angiogenesis. In addition, growth factors which are mediators of this plasticity will be measured using enzyme-linked immunosorbent assay (ELISA). If the treatment combining MSCs with simvastatin is found to be more effective than monotherapy, this will increase the clinical relevance of MSC treatment by allowing us to use smaller and safer doses.

  Funding Agency

Agency
National Institute of Health (NIH)
Institute
National Institute of Neurological Disorders and Stroke (NINDS)
Type
Research Project (R01)
Project #
5R01NS042259-08
Application #
7584025
Study Section
Special Emphasis Panel (ZRG1-BDCN-L (90))
Program Officer
Owens, David F
Project Start
2001-07-01
Project End
2010-02-28
Budget Start
2009-03-01
Budget End
2010-02-28
Support Year
8
Fiscal Year
2009
Total Cost
$283,144
Indirect Cost

  Institution

Name
Henry Ford Health System
Department
Neurosurgery
Type
Schools of Medicine
DUNS #
073134603
City
Detroit
State
MI
Country
United States
Zip Code
48202

  Publications

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
Qu, Changsheng; Mahmood, Asim; Ning, Ruizhuo et al. (2010) The treatment of traumatic brain injury with velcade. J Neurotrauma 27:1625-34
Xiong, Ye; Mahmood, Asim; Chopp, Michael (2010) Neurorestorative treatments for traumatic brain injury. Discov Med 10:434-42
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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