My primary research focus is the assessment of cognitive and motor function impairments in our rhesus monkey models of cortical injury and aging and the underlying neurobiological basis for these impairments. In both models, we are also assessing the efficacy of an exciting new therapeutic, mesenchymal stromal cell derived extracellular vesicles (MSC-EVs), to reverse deficits in cognitive and motor function by decreasing neuroinflammation and myelin pathology.
Our model of cortical injury involves training monkeys on our tasks of fine motor function of the hand, neurosurgical lesion production in primary motor cortex, assessment of recovery of fine motor function and post-perfusion analysis of blood, CSF and brain and spinal cord tissue. This model is used to establish the rate and degree of recovery of function following cortical injury in the aged brain and to investigate the neurobiological basis for recovery. Further, we are assessing the efficacy of MSC-EVs as a restorative treatment to facilitate recovery of function following cortical injury. This work is being conducted in collaboration with researchers at the Henry Ford Health System and the University of Buffalo. To date, we have demonstrated that administration of MSC-EVs, facilitates a complete recovery of fine motor function in the first 3-4 weeks after injury. Further, MSC-EVs reduce injury-induced microglial neuroinflammation, neuronal excitotoxicity, synapse loss, oligodendrocyte damage and myelination deficits. Finally, a recent collaborative proteomic study using a GO analysis of Biological Processes showed that proteins from MSC-EVs are highly specific and involved in signaling pathways for cell-cell adhesion, cell proliferation, extracellular matrix organization, MAPK cascade, Wnt signaling, and small GTPase mediated signal transduction, some of which, play important neuritogenic and synaptogenic roles that could be involved in ameliorating injury-related neurodegeneration and hyperexcitability
In our aging study, we are administering MSC-EVs to aged monkeys following extensive cognitive assessment. After a period of 18 months of treatment, we re-assess the cognitive performance of the monkeys to determine whether the MSC-EVs have slowed or reversed age-related cognitive decline. We also acquire longitudinal MRIs and blood and CSF samples from these monkeys to quantify various biomarkers of inflammation and oxidative damage. Following completion of treatment and cognitive testing, brains will be harvested and analyze for treatment related changes in neuroinflammation and myelin pathology.
- Associate Professor, Neurology, Boston University Chobanian & Avedisian School of Medicine
- Graduate Faculty (Primary Mentor of Grad Students), Boston University Chobanian & Avedisian School of Medicine, Graduate Medical Sciences
- Boston University School of Medicine, PhD
- Univ Calgary, BA
- Published on 9/2/2023
Zhou Y, Bhatt H, Mojica CA, Xin H, Pessina MA, Rosene DL, Moore TL, Medalla M. Mesenchymal-derived extracellular vesicles enhance microglia-mediated synapse remodeling after cortical injury in aging Rhesus monkeys. J Neuroinflammation. 2023 Sep 02; 20(1):201. PMID: 37660145.
- Published on 5/15/2023
Zhou Y, Bhatt H, Mojica CA, Xin H, Pessina M, Rosene DL, Moore TL, Medalla M. Mesenchymal-Derived Extracellular Vesicles Enhance Microglia-mediated Synapse Remodeling after Cortical Injury in Rhesus Monkeys. Res Sq. 2023 May 15. PMID: 37292805.
- Published on 4/28/2023
Moore TL, Medalla M, Ibañez S, Wimmer K, Mojica CA, Killiany RJ, Moss MB, Luebke JI, Rosene DL. Neuronal properties of pyramidal cells in lateral prefrontal cortex of the aging rhesus monkey brain are associated with performance deficits on spatial working memory but not executive function. Geroscience. 2023 Jun; 45(3):1317-1342. PMID: 37106282.
- Published on 4/6/2023
Welke LA, Moore TL, Rosene DL, Killiany RJ, Moss MB. Prefrontal and medial temporal interactions in memory functions in the rhesus monkey. Behav Neurosci. 2023 Jun; 137(3):211-222. PMID: 37023305.
- Published on 2/9/2023
Campbell NB, Patel Y, Moore TL, Medalla M, Zeldich E. Extracellular Vesicle Treatment Alleviates Neurodevelopmental and Neurodegenerative Pathology in Cortical Spheroid Model of Down Syndrome. Int J Mol Sci. 2023 Feb 09; 24(4). PMID: 36834891.
- Published on 2/8/2023
Moore TL, Medalla M, Iba Ez S, Wimmer K, Mojica CA, Killiany RJ, Moss MB, Luebke JI, Rosene DL. Neuronal properties of pyramidal cells in lateral prefrontal cortex of the aging rhesus monkey brain are associated with performance deficits on spatial working memory but not executive function. bioRxiv. 2023 Feb 08. PMID: 36798388.
- Published on 9/13/2022
Baxi M, Cetin-Karayumak S, Papadimitriou G, Makris N, van der Kouwe A, Jenkins B, Moore TL, Rosene DL, Kubicki M, Rathi Y. Investigating the contribution of cytoarchitecture to diffusion MRI measures in gray matter using histology. Front Neuroimaging. 2022; 1:947526. PMID: 37555179.
- Published on 8/18/2022
Calderazzo S, Covert M, Alba D, Bowley BE, Pessina MA, Rosene DL, Buller B, Medalla M, Moore TL. Neural recovery after cortical injury: Effects of MSC derived extracellular vesicles on motor circuit remodeling in rhesus monkeys. IBRO Neurosci Rep. 2022 Dec; 13:243-254. PMID: 36590089.
- Published on 8/5/2022
Dimovasili C, Fair AE, Garza IR, Batterman KV, Mortazavi F, Moore TL, Rosene DL. Aging compromises oligodendrocyte precursor cell maturation and efficient remyelination in the monkey brain. Geroscience. 2023 Feb; 45(1):249-264. PMID: 35930094.
- Published on 5/14/2022
Medalla M, Chang W, Ibañez S, Guillamon-Vivancos T, Nittmann M, Kapitonava A, Busch SE, Moore TL, Rosene DL, Luebke JI. Layer-specific pyramidal neuron properties underlie diverse anterior cingulate cortical motor and limbic networks. Cereb Cortex. 2022 05 14; 32(10):2170-2196. PMID: 34613380.
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