Effect of Early Normobaric Hyperoxia on Blast-Induced Traumatic Brain Injury in Rats

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ORIGINAL PAPER

Effect of Early Normobaric Hyperoxia on Blast‑Induced Traumatic Brain Injury in Rats Yanteng Li1 · Wenying Lv1 · Gang Cheng1 · Shuwei Wang1 · Bangxin Liu2 · Hulin Zhao1 · Hongwei Wang1 · Leiming Zhang1 · Chao Dong1 · Jianning Zhang1  Received: 16 April 2020 / Revised: 28 July 2020 / Accepted: 3 September 2020 © Springer Science+Business Media, LLC, part of Springer Nature 2020

Abstract Blast-induced traumatic brain injury (bTBI) is a leading cause of disability and mortality in soldiers during the conflicts in Iraq and Afghanistan. Although substantial clinical and animal studies have investigated the pathophysiology and treatments of bTBI, few effective therapies have been found, especially for the early rescue in the battlefield. The aim of this study is to evaluate neuroprotective effects of early normobaric hyperoxia (NBO) on bTBI. We established a rat model of bTBI caused by explosion in the cabin. It exhibited typical changes of mild bTBI, like impaired neurological function, brain edema, minor intracranial hemorrhage and neuron necrosis. The rats were divided into 4 groups (n = 12): Sham, Vehicle, hyperbaric oxygen (HBO) and NBO. Neurological function of the rats was assessed by the Neurological Severity Scores (NSS) at 24 h and 72 h after explosion. Serum interleukin-6 (IL-6), neuron specific enolase (NSE) and tau protein were measured at 24 h and 72 h after explosion. Brain water content was measured and Aquaporin-4 (AQP4) immunostaining was performed. Neuronal apoptosis was analyzed by TUNEL staining. NBO demonstrated curative effects on protecting the neurological function. Serum levels of NSE and tau protein were reduced at 24 h and 72 h after explosion. But the levels of IL-6 were not reduced significantly at both time points. Cerebral edema was alleviated. Simultaneously, AQP4 immunostaining of the hippocampus showed remarkably decreased expression after treatment. The number of apoptotic cells in hippocampus was also decreased. Compared with HBO, NBO is simple and convenient, and can be administered in remote areas. It may be a promising therapy for early rescue of bTBI in the battlefield. Keywords  Normobaric hyperoxia · Brain injuries · Blast injuries · Rat · Brain edema

Introduction With the increasing use of explosive munitions, blastinduced traumatic brain injury (bTBI) has become a signature injury of modern warfare. Between 2001 and 2011, 2.2 million service members were deployed in support of Operation Enduring Freedom and Operation Iraqi Freedom, about 20% of whom were diagnosed as bTBI, ranging from Yanteng Li and Wenying Lv have contributed equally to this work. * Jianning Zhang [email protected] 1



Department of Neurosurgery, Sixth Medical Center, Chinese PLA General Hospital, No. 6, Fucheng Road, Haidian District, Beijing 100048, China



Department of Neurosurgery, Central War Zone General Hospital of PLA, Wuhan 430070, China

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mild to severe [1]. According to recent researches, shock wave is the main cause of bTBI. What’s more, explosions often occur in