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Blast-Induced Traumatic Brain Injury Triggered by Moderate Intensity Shock Wave Using a Modified Experimental Model of Injury in Mice.

Abstract：

Background:The increasing frequency of explosive injuries has increased interest in blast-induced traumatic brain injury (bTBI). Various shock tube models have been used to study bTBI. Mild-to-moderate explosions are often overlooked because of the slow onset or mildness of the symptoms. However, heavy gas cylinders and large volume chambers in the model may increase the complexity and danger. This study sought to design a modified model to explore the effect of moderate explosion on brain injury in mice. Methods:Pathology scoring system (PSS) was used to distinguish the graded intensity by the modified model. A total of 160 mice were randomly divided into control, sham, and bTBI groups with different time points. The clinical features, imaging features, neurobehavior, and neuropathology were detected after moderate explosion. One-way analysis of variance followed by Fisher's least significant difference posttest or Dunnett's t 3-test was performed for data analyses. Results:PSS of mild, moderate, and severe explosion was 13.4 ± 2.2, 32.6 ± 2.7 (t = 13.92, P < 0.001; vs. mild group), and 56.6 ± 2.8 (t = 31.37, P < 0.001; vs. mild group), respectively. After moderate explosion, mice showed varied symptoms of malaise, anorexia, incontinence, apnea, or seizure. After bTBI, brain edema reached the highest peak at day 3 (82.5% ± 2.1% vs. 73.8% ± 0.6%, t = 7.76, P < 0.001), while the most serious neurological outcomes occurred at day 1 (Y-maze: 8.25 ± 2.36 vs. 20.00 ± 4.55, t = -4.59, P = 0.048; 29.58% ± 2.84% vs. 49.09% ± 11.63%, t = -3.08, P = 0.008; neurologic severity score: 2.50 ± 0.58 vs. 0.00 ± 0.00, t = 8.65, P = 0.016). We also found that apoptotic neurons (52.76% ± 1.99% vs. 1.30% ± 0.11%, t = 57.20, P < 0.001) and gliosis (2.98 ± 0.24 vs. 1.00 ± 0.00, t = 14.42, P = 0.021) in the frontal were significantly higher at day 3 post-bTBI than sham bTBI. Conclusions:We provide a reliable, reproducible bTBI model in mice that can produce a graded explosive waveform similar to the free-field shock wave in a controlled laboratory environment. Moderate explosion can trigger mild-to-moderate blast damage of the brain. :使用一种改良的冲击波爆炸模型研究中等强度爆炸冲击波对小鼠的脑损伤摘要背景：随着爆炸伤的日益增多，对爆炸性脑损伤（bTBI）的关注也越来越多，很多研究通过不同的冲击波管道模型研究爆炸性脑损伤。轻中强度的爆炸往往因为症状出现慢或轻而容易忽视。然而，我们发现在现有的模型中使用的重型气瓶和大容量腔室可能会增加操作的复杂性和危险性。本研究旨在设计一种方便而安全的小鼠冲击波管道爆炸伤模型，同时研究中强度的爆炸对小鼠脑损伤的影响。方法：使用病理评分系统(PSS)区分改良的小鼠冲击波管道模型制造的轻中重度的爆炸强度。总共160只小鼠随机分为空白组、假爆炸组、爆炸后不同时间点组，我们观察了中等强度的爆炸致bTBI后小鼠的临床症状、影像学表现、神经行为学和神经病理学的变化。我们用单因素方差分析联合Fisher's LSD检验或Dunnett-t3检验来比较各组数据间的差异。结果：轻中重强度的冲击波对应的PSS分别为13.4±2.2、32.6±2.7(t=13.92, P<0.001)和56.6±2.8 (t=31.37, P<0.001)。遭受中等强度的冲击波刺激后，小鼠表现为不同程度的萎靡不振、厌食、尿失禁、呼吸暂停和癫痫。与假爆炸组相比，bTBI后3天脑水肿达到高峰(82.5±2.1% vs. 73.8±0.6%, t=7.76, P<0.001)，而bTBI后1天神经行为损伤最严重(Y迷宫：8.25±2.36 vs. 20.00±4.55, t=-4.59, P=0.048; 29.58±2.84% vs. 49.09±11.63%, t=-3.08, P=0.008; 神经严重程度评分：2.50±0.58 vs. 0.00±0.00, t=8.65, P=0.016)。同时我们发现，额叶的凋亡的神经元 (52.76±1.99% vs. 1.30±0.11%, t=57.20, P<0.001)和神经胶质增生(2.98±0.24 vs. 1.00±0.00, t=14.42, P=0.021)在bTBI后3天明显多于假爆炸组。结论：我们改良了一种可靠的、重复性好的小鼠bTBI模型，能够在可控的实验室环境下产生类似于自由场冲击波的分级的爆炸波形；中等强度的爆炸冲击波可能导致了小鼠轻中度的脑损伤。.

journal_name

Chin Med J (Engl)

journal_title

Chinese medical journal

authors

Zhou Y,Wen LL,Wang HD,Zhou XM,Fang J,Zhu JH,Ding K

doi

10.4103/0366-6999.243558

subject

Has Abstract

pub_date

2018-10-20 00:00:00

pages

2447-2460

issue

eissn

0366-6999

issn

2542-5641

pii

ChinMedJ_2018_131_20_2447_243558

journal_volume

131

pub_type

杂志文章

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Blast-Induced Traumatic Brain Injury Triggered by Moderate Intensity Shock Wave Using a Modified Experimental Model of Injury in Mice.