Constraint-Induced Movement Therapy (CIMT) and Neural Precursor Cell (NPC) Transplantation Synergistically Promote Anatomical and Functional Recovery in a Hypoxic-Ischemic Mouse Model
Abstract
:1. Introduction
2. Results
2.1. Transplanted NPCs Survive, Migrate, Differentiate Morphologically, and Integrate in the Corpus Callosum
2.2. Transplanted NPCs, CIMT, and NPC + CIMT Lead to Structural Recovery
2.2.1. Neonatal HI Reduces the Overall Brain Size, but No Treatments Restore It
2.2.2. HI Injury Significantly Affects the Hippocampus, and Treatments Mitigate the Damage
2.2.3. HI Injury Affects the Cortex, and Treatment Produces Significant Recovery
2.2.4. HI Injury Significantly Affects the Corpus Callosum, and Treatment with NPCs and CIMT Leads to Recovery
2.2.5. HI Injury Notably Affects the Lateral Ventricle, and Treatment with NPCs and CIMT Leads to Significant Recovery
2.3. Transplanted NPCs, CIMT, and the Combination of These Modalities Leads to Myelination
2.3.1. Following HI, Treatment with NPCs and CIMT Restored the Endogenous OL Population above the Normal Level, While the Mature OL Population Was Normalized
2.3.2. HI Injury Significantly Affects Myelination of the CC and Treatment with NPCs and CIMT Leads to Functional Myelination
2.4. Transplanted NPC, CIMT, and NPC + CIMT Treatments Led to Functional Recovery
2.4.1. Cylinder Test
2.4.2. CatWalk Gait Assessment
Swing Speed
Stride Length
Paw Intensity
3. Discussion
3.1. Transplanted NPCs Survive, Differentiate Morphologically, and Engraft in Brain Tissue
3.2. NPC Transplantation Leads to Structural and Functional Improvement
3.3. CIMT Also Leads to Structural and Functional Improvement
3.4. NPCs and CIMT in Combination Have a Synergistic Effect on Functional Recovery
4. Materials and Methods
4.1. Animal Use
4.2. Study Design
4.3. Hypoxia-Ischemia Model of Hemiplegic Perinatal Brain Injury
4.4. Adult NPC Transplantation
4.5. Constraint-Induced Movement Therapy (CIMT)
4.6. Structural Assessment
4.6.1. Tissue Preparation
4.6.2. Immunostaining and Histology
4.6.3. Quantification
4.7. Functional Assessment: Electrophysiology
4.8. Functional Assessment: Neurobehavioural Testing
4.8.1. The Cylinder Test
4.8.2. The CatWalk Gait Test
4.9. Statistical Analysis
Supplementary Materials
Author Contributions
Funding
Institutional Review Board Statement
Informed Consent Statement
Data Availability Statement
Acknowledgments
Conflicts of Interest
References
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Rumajogee, P.; Altamentova, S.; Li, J.; Puvanenthirarajah, N.; Wang, J.; Asgarihafshejani, A.; Van Der Kooy, D.; Fehlings, M.G. Constraint-Induced Movement Therapy (CIMT) and Neural Precursor Cell (NPC) Transplantation Synergistically Promote Anatomical and Functional Recovery in a Hypoxic-Ischemic Mouse Model. Int. J. Mol. Sci. 2024, 25, 9403. https://doi.org/10.3390/ijms25179403
Rumajogee P, Altamentova S, Li J, Puvanenthirarajah N, Wang J, Asgarihafshejani A, Van Der Kooy D, Fehlings MG. Constraint-Induced Movement Therapy (CIMT) and Neural Precursor Cell (NPC) Transplantation Synergistically Promote Anatomical and Functional Recovery in a Hypoxic-Ischemic Mouse Model. International Journal of Molecular Sciences. 2024; 25(17):9403. https://doi.org/10.3390/ijms25179403
Chicago/Turabian StyleRumajogee, Prakasham, Svetlana Altamentova, Junyi Li, Nirushan Puvanenthirarajah, Jian Wang, Azam Asgarihafshejani, Derek Van Der Kooy, and Michael G. Fehlings. 2024. "Constraint-Induced Movement Therapy (CIMT) and Neural Precursor Cell (NPC) Transplantation Synergistically Promote Anatomical and Functional Recovery in a Hypoxic-Ischemic Mouse Model" International Journal of Molecular Sciences 25, no. 17: 9403. https://doi.org/10.3390/ijms25179403