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A Versatile Murine Model of Subcortical White Matter Stroke for the Study of Axonal Degeneration and White Matter Neurobiology
Published on: March 17, 2016
MRI detects white matter reorganization after neural progenitor cell treatment of stroke
Quan Jiang1, Zheng Gang Zhang, Guang Liang Ding
1Department of Neurology, Henry Ford Health Sciences Center, Henry Ford Hospital, 2799 West Grand Boulevard, Detroit, MI 48202, USA. quan@neurnis.neuro.hfh.edu
Abstract:
We evaluated the effects of neural progenitor cell treatment of stroke on white matter reorganization using MRI. Male Wistar rats (n = 26) were subjected to 3 h of middle cerebral artery occlusion and were treated with neural progenitor cells (n = 17) or without treatment (n = 9) and were sacrificed at 5-7 weeks thereafter. MRI measurements revealed that grafted neural progenitor cells selectively migrated towards the ischemic boundary regions. White matter reorganization, confirmed histologically, was coincident with increases of fractional anisotropy (FA, P < 0.01) after stroke in the ischemic recovery regions compared to that in the ischemic core region in both treated and control groups. Immunoreactive staining showed axonal projections emanating from neurons and extruding from the corpus callosum into the ipsilateral striatum bounding the lesion areas after stroke. Fiber tracking (FT) maps derived from diffusion tensor imaging revealed similar orientation patterns to the immunohistological results. Complementary measurements in stroke patients indicated that FT maps exhibit an overall orientation parallel to the lesion boundary. Our data demonstrate that FA and FT identify and characterize cerebral tissue undergoing white matter reorganization after stroke and treatment with neural progenitor cells.
Insights
Neural progenitor cell treatment aids brain repair after stroke by promoting white matter reorganization. Magnetic Resonance Imaging (MRI) and advanced imaging techniques like fractional anisotropy (FA) and fiber tracking (FT) show significant recovery in stroke models and patients.
Area of Science:
- Neuroscience
- Regenerative Medicine
- Medical Imaging
Background:
- Stroke is a leading cause of long-term disability, often resulting in white matter damage.
- Neural progenitor cell (NPC) transplantation is a promising therapeutic strategy for stroke recovery.
- Understanding the mechanisms of white matter reorganization post-stroke is crucial for developing effective treatments.
Purpose of the Study:
- To evaluate the effects of NPC treatment on white matter reorganization after stroke using MRI.
- To investigate the migratory patterns of transplanted NPCs in the stroke-affected brain.
- To correlate imaging findings with histological evidence of white matter repair.
Main Methods:
- Middle cerebral artery occlusion (MCAO) model in Wistar rats, followed by NPC transplantation or sham treatment.
- Magnetic Resonance Imaging (MRI) including diffusion tensor imaging (DTI) to assess white matter integrity.
- Histological analysis and immunohistochemical staining to confirm cellular infiltration and axonal projections.
- Analysis of fractional anisotropy (FA) and fiber tracking (FT) maps.
Main Results:
- Transplanted NPCs migrated to ischemic boundary regions.
- Significant increases in fractional anisotropy (FA) were observed in ischemic recovery regions, indicating white matter reorganization (P < 0.01).
- Immunohistochemistry and fiber tracking (FT) revealed axonal projections from the corpus callosum into the striatum, aligning with histological findings.
- FT maps in stroke patients showed orientation parallel to the lesion boundary.
Conclusions:
- Fractional anisotropy (FA) and fiber tracking (FT) are effective imaging biomarkers for detecting and characterizing white matter reorganization after stroke.
- NPC treatment promotes white matter reorganization in the stroke-affected brain.
- These findings support the potential of NPC therapy and advanced MRI techniques in stroke rehabilitation research.

