Oral ascorbic acid 2-glucoside prevents coordination disorder induced via laser-induced shock waves in rat brain.

Takaaki Maekawa,Yuka Nakata-Horiuchi,Takahiro Uchida,Shunichi Sato,Satoko Kawauchi,Hiroaki Kobayashi,Manabu Kinoshita,Daizoh Saitoh,Alfred S Lewin

doi:10.1371/journal.pone.0230774

Abstract

Oxidative stress is considered to be involved in the pathogenesis of primary blast-related traumatic brain injury (bTBI). We evaluated the effects of ascorbic acid 2-glucoside (AA2G), a well-known antioxidant, to control oxidative stress in rat brain exposed to laser-induced shock waves (LISWs). The design consisted of a controlled animal study using male 10-week-old Sprague-Dawley rats. The study was conducted at the University research laboratory. Low-impulse (54 Pa•s) LISWs were transcranially applied to rat brain. Rats were randomized to control group (anesthesia and head shaving, n = 10), LISW group (anesthesia, head shaving and LISW application, n = 10) or LISW + post AA2G group (AA2G administration after LISW application, n = 10) in the first study. In another study, rats were randomized to control group (n = 10), LISW group (n = 10) or LISW + pre and post AA2G group (AA2G administration before and after LISW application, n = 10). The measured outcomes were as follows: (i) motor function assessed by accelerating rotarod test; (ii) levels of 8-hydroxy-2'-deoxyguanosine (8-OHdG), an oxidative stress marker; (iii) ascorbic acid in each group of rats. Ascorbic acid levels were significantly decreased and 8-OHdG levels were significantly increased in the cerebellum of the LISW group. Motor coordination disorder was also observed in the group. Prophylactic AA2G administration significantly increased the ascorbic acid levels, reduced oxidative stress and mitigated the motor dysfunction. In contrast, the effects of therapeutic AA2G administration alone were limited. The results suggest that the prophylactic administration of ascorbic acid can reduce shock wave-related oxidative stress and prevented motor dysfunction in rats.

Highlights

Blast injury has been a constant threat in recent conflicts because of frequent terrorist attacks using weapons such as improvised explosive devices (IEDs)
In this study, considering the ability to exert strong antioxidant activity by acting as free radical scavenger [26,27,28,29], we evaluated the effects of ascorbic acid 2-glucoside (AA2G), a stable derivative of ascorbic acid which is generated by binding glucose to conventional ascorbic acid [30], on the laser-induced shock waves (LISWs)-induced TBI model
These results showed that this LISW-induced TBI model was characterized by oxidative stress in the brains and prompted us to evaluate the effects of AA2G on the model, especially focusing on cerebellar oxidative stress

Summary

Introduction

Blast injury has been a constant threat in recent conflicts because of frequent terrorist attacks using weapons such as improvised explosive devices (IEDs). These changes of combat style affect both civilian and military populations and result in a large number of patients suffering from blast-related traumatic brain injury (bTBI) [1,2,3]. NOX is upregulated in multiple brain regions following blast injury, and neurons maximally contributes to a higher increase in the hippocampus compared with other neural cells [16, 17]. Oxidative stress contributes to enhanced BBB permeability during bTBI via a pathway that involves increased matrix metalloproteinase activation [18]

Methods

Results

Discussion

Conclusion