There are two major innovative aspects to our proposal: 1) To develop magnetic resonance imaging (MRI) as a means to monitor and predict functional recovery after traumatic brain injury (TBI);and 2) To treat TBI with bone marrow stromal cells (MSCs) early, i.e. within 24 hours of injury, as a neuroprotective and neurorestorative therapy. Neurorestorative treatment of TBI using MSCs has demonstrated promise in promoting neuronal remodeling, and improvement of functional recovery. However, we and others have not studied the beneficial effects of early, within 24 hours of injury, treatment with MSCs. Also, there is a compelling need to noninvasively monitor brain remodeling and functional recovery and to translate these methodologies from experimental studies to the clinic. We propose that MRI can sensitively monitor ongoing structural remodeling of brain tissue after TBI that reflects neurological function, and therefore, MRI can be employed to assess recovery and ultimately be applied to the TBI patient. In this proposal, we will develop and implement MR methodologies to investigate the effects of early and late MSC treatment on the migration and distribution of MSCs and lesion volume after TBI (Aim 1), neurite reorganization (Aim 2), and the relationship between brain remodeling and functional recovery (Aim 3) in the experimental animal subjected to TBI. MRI measurements of brain remodeling will be verified using three dimensional laser scanning confocal microscopy and immuno-histochemistry. Neurological outcome will be assessed using a battery of behavioral tests. With these novel approaches, we expect that MRI methodologies for measurement of distribution and concentration of MSCs and neurite reorganization are valid new tools for monitoring the recovery from TBI after restorative therapy. These methods should lead to optimization of treatment protocols and improved management of recovery from TBI.

Public Health Relevance

The investigation of early MSC therapy of TBI utilizing MR-measures of brain neurite reorganization and bone marrow stromal cell (MSC) distribution for predicting brain functional recovery after traumatic brain injury (TBI) and could promise new patient therapies aimed at improving TBI recovery. These studies have the potential to greatly enhance neurological outcomes from TBI and to noninvasively monitor the associated neurite reorganization leading to the recovery of functions.

Agency
National Institute of Health (NIH)
Institute
National Institute of Neurological Disorders and Stroke (NINDS)
Type
Research Project (R01)
Project #
1R01NS064134-01A2
Application #
8184116
Study Section
Acute Neural Injury and Epilepsy Study Section (ANIE)
Program Officer
Hicks, Ramona R
Project Start
2011-06-15
Project End
2015-05-31
Budget Start
2011-06-15
Budget End
2012-05-31
Support Year
1
Fiscal Year
2011
Total Cost
$320,372
Indirect Cost
Name
Henry Ford Health System
Department
Type
DUNS #
073134603
City
Detroit
State
MI
Country
United States
Zip Code
48202
Li, Lian; Chopp, Michael; Ding, Guangliang et al. (2017) Diffusion-Derived Magnetic Resonance Imaging Measures of Longitudinal Microstructural Remodeling Induced by Marrow Stromal Cell Therapy after Traumatic Brain Injury. J Neurotrauma 34:182-191
Ding, Guangliang; Chen, Jieli; Chopp, Michael et al. (2017) White matter changes after stroke in type 2 diabetic rats measured by diffusion magnetic resonance imaging. J Cereb Blood Flow Metab 37:241-251
Jiang, Quan; Zhang, Li; Ding, Guangliang et al. (2017) Impairment of the glymphatic system after diabetes. J Cereb Blood Flow Metab 37:1326-1337
Nejad-Davarani, Siamak P; Bagher-Ebadian, Hassan; Ewing, James R et al. (2017) A parametric model of the brain vascular system for estimation of the arterial input function (AIF) at the tissue level. NMR Biomed 30:
Nejad-Davarani, Siamak P; Bagher-Ebadian, Hassan; Ewing, James R et al. (2017) An extended vascular model for less biased estimation of permeability parameters in DCE-T1 images. NMR Biomed 30:
Li, Lian; Chopp, Michael; Ding, Guangliang et al. (2017) Chronic global analysis of vascular permeability and cerebral blood flow after bone marrow stromal cell treatment of traumatic brain injury in the rat: A long-term MRI study. Brain Res 1675:61-70
Jiang, Quan (2016) Magnetic resonance imaging and cell-based neurorestorative therapy after brain injury. Neural Regen Res 11:7-14
Nejad-Davarani, Siamak P; Chopp, Michael; Peltier, Scott et al. (2016) Resting state fMRI connectivity analysis as a tool for detection of abnormalities in five different cognitive networks of the brain in Multiple Sclerosis patients. Clin Case Rep Rev 2:464-471
Ding, Guangliang; Chen, Jieli; Chopp, Michael et al. (2016) Cell Treatment for Stroke in Type Two Diabetic Rats Improves Vascular Permeability Measured by MRI. PLoS One 11:e0149147
Ding, Guangliang; Yan, Tao; Chen, Jieli et al. (2015) Persistent cerebrovascular damage after stroke in type two diabetic rats measured by magnetic resonance imaging. Stroke 46:507-12

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