# Neural substrates of exosome-mediated enhancement of recovery after cortical injury in non-human primates.

> **NIH NIH R56** · BOSTON UNIVERSITY MEDICAL CAMPUS · 2020 · $561,250

## Abstract

Abstract The efficacy of exosomes harvested from mesenchymal stromal cells (MSCs) to enhance recovery
has been demonstrated in rodent models of stroke (1-3). Building on this, we showed following cortical injury in
monkeys that exosomes harvested from monkey MSCs facilitate recovery within 3-5 weeks(5). Here we propose
to now conduct an analysis of the time course and mechanisms underlying exosome-mediated recovery. In
previous studies, we harvested brain tissue at 14 weeks post-injury, at which time markers of acute inflammation
and repair processes have stabilized. Additionally, our recent findings show a marked difference in the time
course of recovery, with exosome-treated monkeys exhibiting full recovery by 3-5 weeks post-injury and
untreated animals reaching a plateau in recovery by 8-12 weeks. To better understand the effects on both
inflammation and plasticity, we now propose to harvest brains at 4 and 8 weeks post-injury while collecting blood
and CSF at multiple time points to investigate temporal changes in biomarkers that underlie recovery. We
hypothesize that exosomes will limit acute damage after cortical injury by acting on microglia and other brain
cells to promote a switch from pro-inflammatory to anti-inflammatory phenotypes, and transition to a restorative
microenvironment. We will test this hypothesis by comparing the recovery of function with and without the
administration of exosomes following unilateral cortical injury limited to the hand representation. Following
treatment, monkeys will be tested on our motor tasks for either 4 or 8 weeks to assess recovery. After completing
testing, monkeys will undergo multi-dimensional diffusion MRI to assess the microstructure of the brain. Brains
will then be harvested in order to comprehensively investigate the effect of exosomes on injury-related
inflammation and repair processes in several ways. We will assess changes in molecular markers of
inflammation, myelin damage, and repair in blood, CSF, and brain tissue and test the effects of exosomes on
microglia in vitro. Blood and CSF and brain tissue lysates will be used for ELISA quantification of inflammatory
and trophic markers and associated changes in gene expression will be assessed with qPCR. We will also use
immunohistochemistry to quantify markers of microglia (LN3, P2YR12, IBA1) and synaptic (VGAT and VGLUTs)
and neurite (GAP-43, MAP2) remodeling, and label-free spectral confocal reflectance (SCoRe) microscopy to
assess myelin integrity. Then to mechanistically determine the action of exosomes, we will assess the direct
effects of exosomes in in vitro, using oxygen glucose deprivation in acute brain slices. In addition, we will assess
the effects of exosomes on injury-related changes in neuronal morphology, excitability and signaling by
comparing the neurophysiological properties of pyramidal neurons using whole-cell patch-clamp recordings and
intracellular filling in acute brain slices. Finally, we will conduct a proteomics...

## Key facts

- **NIH application ID:** 10131293
- **Project number:** 1R56NS112207-01A1
- **Recipient organization:** BOSTON UNIVERSITY MEDICAL CAMPUS
- **Principal Investigator:** TARA L MOORE
- **Activity code:** R56 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2020
- **Award amount:** $561,250
- **Award type:** 1
- **Project period:** 2020-04-15 → 2022-03-31

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/10131293

## Citation

> US National Institutes of Health, RePORTER application 10131293, Neural substrates of exosome-mediated enhancement of recovery after cortical injury in non-human primates. (1R56NS112207-01A1). Retrieved via AI Analytics 2026-05-28 from https://api.ai-analytics.org/grant/nih/10131293. Licensed CC0.

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