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J Neurotrauma. 2019 Nov 27. doi: 10.1089/neu.2019.6443. [Epub ahead of print]

Extracellular vesicles mediate neuroprotection and functional recovery after traumatic brain injury.

Author information

1
University of Georgia, Regenerative Bioscience Center, ADS, Athens, Georgia, United States.
2
University of Georgia, Biomedical and Health Sciences Institute , Athens, Georgia, United States; ms91136@uga.edu.
3
University of Georgia, Biomedical and Health Sciences Institute , Athens, Georgia, United States; passaroa@uga.edu.
4
University of Georgia, 1355, Department of Animal and Dairy Science, Athens, Georgia, United States; latchoumane.c@uga.edu.
5
University of Georgia, Biomedical and Health Sciences Institute , Athens, Georgia, United States; samantha.spellicy25@uga.edu.
6
University of Georgia, 186969, Department of Biochemistry and Molecular Biology, Athens, Georgia, United States; michaelbowler@uga.edu.
7
University of Georgia, 1355, Department of Biochemistry and Molecular Biology, Athens, Georgia, United States; morgan.goeden25@uga.edu.
8
University of Georgia, 1355, Animal Health Research Center , Athens, Georgia, United States; wmartin3@uga.edu.
9
University of Georgia, Department of Psychology, Athens, Georgia, United States.
10
University of Georgia, Biomedical and Health Sciences Institute , Athens, Georgia, United States; pvholmes@uga.edu.
11
University of Georgia, Biomedical and Health Sciences Institute , Athens, Georgia, United States.
12
University of Georgia, Department of Animal and Dairy Science, Athens, Georgia, United States; sstice@uga.edu.
13
University of Georgia, Department of Animal and Dairy Science, Athens, Georgia, United States; lohitash@uga.edu.

Abstract

The lack of effective therapies for moderate-to-severe traumatic brain injures (TBIs) leaves patients with lifelong disabilities. Neural stem cells (NSCs) have demonstrated great promise for neural repair and regeneration. However, direct evidence to support their use as a cell-replacement therapy for neural injuries is currently lacking. We hypothesized that NSC-derived extracellular vesicles (NSC EVs) mediate repair indirectly after TBI by enhancing neuroprotection and therapeutic efficacy of endogenous NSCs. We evaluated the short-term effects of acute intravenous injections of NSC EVs immediately following a rat TBI. Male NSC EV-treated rats demonstrated significantly reduced lesion sizes, enhanced presence of endogenous NSCs, and attenuated motor function impairments four weeks post-TBI, when compared to vehicle- and TBI-only male controls. Although statistically not significant, we observed a therapeutic effect of NSC EVs on brain lesion volume, nestin expression and behavioral recovery in female subjects. Our study demonstrates the neuroprotective and functional benefits of NSC EVs for treating TBI and points to gender-dependent effects on treatment outcomes, which requires further investigation.

KEYWORDS:

RECOVERY; Rat; STEM CELLS; TRAUMATIC BRAIN INJURY

PMID:
31774030
DOI:
10.1089/neu.2019.6443

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