Mesenchymal-Stem-Cell-Derived Extracellular Vesicles Attenuate Brain Injury in Escherichia coli Meningitis in Newborn Rats

Abstract

We recently reported that transplantation of mesenchymal stem cells (MSCs) significantly reduced bacterial growth and brain injury in neonatal meningitis induced by Escherichia coli (E. coli) infection in newborn rats. As a next step, to verify whether the MSCs protect against brain injury in a paracrine manner, this study was designed to estimate the efficacy of MSC-derived extracellular vesicles (MSC-EVs) in E. coli meningitis in newborn rats. E. coli meningitis was induced without concomitant bacteremia by the intra-cerebroventricular injection of 5 × 102 colony-forming units of K1 (-) E. coli in rats, at postnatal day 11. MSC-EVs were intra-cerebroventricularly transplanted 6 h after the induction of meningitis, and antibiotics were administered for three consecutive days starting at 24 h after the induction of meningitis. The increase in bacterial growth in the cerebrospinal fluid measured at 24 h after the meningitis induction was not significantly reduced following MSC-EV transplantation. However, an increase in brain cell death, reactive gliosis, and inflammation following meningitis were significantly attenuated after MSC-EV transplantation. Taken together, our results indicate that MSCs show anti-apoptotic, anti-gliosis, and anti-inflammatory, but not antibacterial effects, in an EV-mediated paracrine manner in E. coli-induced neonatal meningitis.