Department of Neurosurgery, Jinling Hospital, Jinling School of Clinical Medicine, Nanjing Medical University, Jiangsu, Nanjing 210002, China.
Chin Med J (Engl). 2018 Oct 20;131(20):2447-2460. doi: 10.4103/0366-6999.243558.
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.
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.
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.
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.
爆炸伤的频率不断增加，人们对爆炸引起的创伤性脑损伤（bTBI）越来越感兴趣。各种激波管模型已被用于研究 bTBI。由于症状的潜伏期或轻微性，轻度至中度爆炸往往被忽视。然而，模型中的重型气罐和大容量室可能会增加复杂性和危险性。本研究旨在设计一种改良模型，以探讨中度爆炸对小鼠脑损伤的影响。
采用改良模型的病理评分系统（PSS）区分分级强度。将 160 只小鼠随机分为对照组、假手术组和 bTBI 组，不同时间点进行检测。中度爆炸后检测临床特征、影像学特征、神经行为和神经病理学变化。采用单因素方差分析，然后采用 Fisher 最小显著差检验或 Dunnett's t 3 检验进行数据分析。
轻度、中度和重度爆炸的 PSS 分别为 13.4 ± 2.2、32.6 ± 2.7（t = 13.92，P < 0.001；与轻度组相比）和 56.6 ± 2.8（t = 31.37，P < 0.001；与轻度组相比）。中度爆炸后，小鼠出现不同程度的不适、食欲不振、失禁、呼吸暂停或抽搐等症状。bTBI 后，脑水肿在第 3 天达到高峰（82.5% ± 2.1%比 73.8% ± 0.6%，t = 7.76，P < 0.001），而最严重的神经学结果发生在第 1 天（Y 迷宫：8.25 ± 2.36 比 20.00 ± 4.55，t = -4.59，P = 0.048；29.58% ± 2.84%比 49.09% ± 11.63%，t = -3.08，P = 0.008；神经严重程度评分：2.50 ± 0.58 比 0.00 ± 0.00，t = 8.65，P = 0.016）。我们还发现，中度爆炸后第 3 天，额叶的凋亡神经元（52.76% ± 1.99%比 1.30% ± 0.11%，t = 57.20，P < 0.001）和神经胶质增生（2.98 ± 0.24 比 1.00 ± 0.00，t = 14.42，P = 0.021）明显高于假手术组。
我们提供了一种可靠的、可重复的小鼠 bTBI 模型，可以在受控的实验室环境中产生类似于自由场冲击波的分级爆炸波形。中度爆炸可引发轻度至中度的脑爆震损伤。
