ESTABLISHING MAGNETIC RESONANCE IMAGING METHODOLOGY TO MONITOR STRUCTURAL CHANGES IN THE BRAIN AFTER NEURAL STEM CELL TRANSPLANTATION IN AGED RATS

picture of Abhishek Umashankar presenting his/her poster: ESTABLISHING MAGNETIC RESONANCE IMAGING METHODOLOGY TO MONITOR STRUCTURAL CHANGES IN THE BRAIN AFTER NEURAL STEM CELL TRANSPLANTATION IN AGED RATS

Abhishek Umashankar , Ted Trouard, Mandi Corenblum, Lalitha Madhavan

ESTABLISHING MAGNETIC RESONANCE IMAGING METHODOLOGY TO MONITOR STRUCTURAL CHANGES IN THE BRAIN AFTER NEURAL STEM CELL TRANSPLANTATION IN AGED RATS

The development of therapies for age-related neurodegenerative disorders, such as Parkinson’s Disease (PD), using stem cells, requires a thorough understanding of how such cells survive and function in an aging brain environment.  Therefore, the broad goal of our studies is to investigate from several viewpoints, how neural aging and stem cells can influence each other, and how stem cells can benefit an aging neural environment.  Our aim here was to establish some baseline parameters for using Magnetic Resonance Imaging (MRI) as a non-invasive method to monitor structural changes in the brain after neural stem cell (NSC) transplantation.  Aged (22 months) Fisher 344 rats were transplanted stereotaxically with 100,000 NSCs or alternatively injected with Hanks Balanced Salt Solution (HBSS, vehicle) in the substantia nigra and striatum (brain regions relevant to PD), and studied in conjunction with untreated (naïve) animals.  All animals were subjected to high resolution MRI scanning via a 7T Bruker BIOSPEC MRI instrument at 1 day prior to NSC transplantation, and subsequently at 2 weeks and 2 months after transplantation.  Both T2 weighted volumetric MRI and Diffusion Tensor Imaging (DTI) were performed, after which animals were sacrificed for histological analysis.  The T2 weighted volumetric images were processed using the program MRIcron.  The data showed that the scans of vehicle injected and untreated rats appear structurally similar, with only local differences at the injection site, indicating that the injury induced by stereotaxic injection is not a confounding factor in the experiment as it independently does not alter brain structure.  The DTI images were processed using DTI studios software, and methods for generating FA values (measure of white matter integrity) as well as fiber trackings of the corpus callosum and nigrostriatal tracts were determined.  Also, histological analysis revealed the presence of transplanted NSCs in both the striatum and substantia nigra at the 2 month time-point.  Overall, these studies (1) determine that NSCs can survive in the aging brain for an extended time, and (2) create some reference protocols for MRI acquisition and analysis to monitor structural alterations in the brain after NSC transplantation.

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