EXTRACELLULAR VESICLE TREATMENT REDUCES INFLAMMATION AND INCREASES NEURONAL MARKERS IN A MONKEY MODEL OF CORTICAL INJURY
Recommended Citation
McCann R, Zhou Y, Mojica C, Zledich E, Xin H, Rosene D, Medalla M, Moore T. EXTRACELLULAR VESICLE TREATMENT REDUCES INFLAMMATION AND INCREASES NEURONAL MARKERS IN A MONKEY MODEL OF CORTICAL INJURY. J Neurotrauma 2023; 40(15-16):A108-A109.
Document Type
Conference Proceeding
Publication Date
8-1-2023
Publication Title
J Neurotrauma
Abstract
Cortical injuries can result in major functional disability, but there are no approved therapeutic interventions. In our rhesus monkey model of cortical injury, treatment with mesenchymal stromal cell‐derived extracellular vesicles (MSC‐EVs) facilitated full recovery of fine motor function 3‐5 weeks after injury to primary motor cortex. However, the recovery mechanism for animals treated with MSC‐EVs remains unclear. Here we examined biomarkers of inflammation and damage in CSF and plasma across the recovery period of aged female rhesus monkeys after cortical injury, with (n = 4) or without (n = 4) treatment with MSC‐EVs. With the Olink multiplex proteomic assay of inflammatory markers in plasma, we found an overall suppression of the immune response in treated animals (CX3CL1: p = 0.02, NT3: p = 0.007). Using an ELISA, we found an unexpected increase in neurofilament light chain (NF‐L), a marker correlated with neuronal damage, in MSC‐EV treated monkeys. Greater levels of NF‐L can either mean increased damage in the brain, or increased clearance. We examined brain tissue harvested 6‐weeks post‐injury and used immunohistochemistry to assess microglia and cytoskeletal neuronal integrity. Analyses of microglial protein expression in a subset of the animals showed a trend towards lower immune activation in white matter of treated monkeys (p < 0.1). Further, we found greater microtubule associated protein (MAP2) labeling, indicative of greater neuronal integrity (less damage), in perilesional grey matter of treated monkeys (p < 0.05). This data suggests that MSC‐EVs suppress the inflammatory response and promote neuronal integrity, likely through increased clearance of damaged tissue following cortical injury. Funding: R01AG068168, R56NS112207, R21NS102991, R21NS111174, R01AG078460
Volume
40
Issue
15-16
First Page
A108
Last Page
A109
