Administration of Oxygen Ultra-Fine Bubbles Improves Nerve Dysfunction in a Rat Sciatic Nerve Crush Injury Model.

Hozo Matsuoka,Kosuke Ebina,Tsuyoshi Murase,Shunsuke Nishimoto,Takaaki Noguchi,Hideki Yoshikawa,Hiroyuki Tanaka,Makoto Hirao,Koji Suzuki,Toru Iwahashi

doi:10.3390/ijms19051395

Abstract

Ultra-fine bubbles (<200 nm in diameter) have several unique properties and have been tested in various medical fields. The purpose of this study was to investigate the effects of oxygen ultra-fine bubbles (OUBs) on a sciatic nerve crush injury (SNC) model rats. Rats were intraperitoneally injected with 1.5 mL saline, OUBs diluted in saline, or nitrogen ultra-fine bubbles (NUBs) diluted in saline three times per week for 4 weeks in four groups: (1) control, (sham operation + saline); (2) SNC, (crush + saline); (3) SNC+OUB, (crush + OUB-saline); (4) SNC+NUB, (crush + NUB-saline). The effects of the OUBs on dorsal root ganglion (DRG) neurons and Schwann cells (SCs) were examined by serial dilution of OUB medium in vitro. Sciatic functional index, paw withdrawal thresholds, nerve conduction velocity, and myelinated axons were significantly decreased in the SNC group compared to the control group; these parameters were significantly improved in the SNC+OUB group, although NUB treatment did not affect these parameters. In vitro, OUBs significantly promoted neurite outgrowth in DRG neurons by activating AKT signaling and SC proliferation by activating ERK1/2 and JNK/c-JUN signaling. OUBs may improve nerve dysfunction in SNC rats by promoting neurite outgrowth in DRG neurons and SC proliferation.

Highlights

Ultra-fine bubbles (UFBs), referred to as nanobubbles, are miniature gas bubbles
The rats were given 1.5 mL saline, oxygen ultra-fine bubbles (OUBs) diluted in saline, or nitrogen ultra-fine bubbles (NUBs) diluted in saline by intraperitoneal injection three times per week for 4 weeks on the day after crush or sham operation
OUB treatment prevented these reductions in the sciatic functional index (SFI) (SNC vs. sciatic nerve crush injury (SNC)+OUB: −27.0 vs. −11.3; p < 0.001), NUB treatment had no significant effects compared to the SNC group (Figure 1A)

Summary

Introduction

Ultra-fine bubbles (UFBs), referred to as nanobubbles, are miniature gas bubbles 50 μm in diameter), increase in size and rapidly burst at the surface of liquids [3,4]. Previous reports have demonstrated that UFBs increase the oxygen pressure in liquids to a greater extent than microbubbles (10–50 μm in diameter) [1,4], and the high oxygen gas solubility of UFBs can be beneficial for oxygenation of hypoxic tissues [5,6,7]. No reports have assessed the effects of OUBs on the nervous system

Objectives

Methods

Results