AbstractBlast neurotrauma has been linked to impairments in higher-order cognitive functions, including memory, attention, and mood. Current literature is limited to a single overpressure exposure or repeated exposures at the same level of overpressure. In this study, a rodent model of primary blast neurotrauma was employed to determine the pressure at which acute and chronic neurological alterations occurred.

摘要神经创伤与高阶认知功能受损有关，包括记忆，注意力和情绪。目前的文献仅限于单一超压暴露或相同超压水平的重复暴露。在这项研究中，采用原发性爆炸性神经创伤的啮齿动物模型来确定发生急性和慢性神经系统改变的压力。

Three pressure magnitudes (low, moderate and high) were used to evaluate injury thresholds. A biology shock tube (BST) was used to simulate shock waves with overpressures of 60 kPa, 90 kPa and 120 kPa respectively. Neurological behavior of the rats was assessed by the Multi-Conditioning System (MCS) at 1 d, 7 d, 28 d and 90 d after shock wave exposure.

使用三个压力大小（低，中和高）来评估损伤阈值。采用生物激波管（BST）模拟了超压分别为60 kPa、90 kPa和120 kPa的激波。在冲击波暴露后1天，7天，28天和90天，通过多调节系统（MCS）评估大鼠的神经行为。

Serum dopamine (DA), 5-hydroxytryptamine (5-HT), brain-derived neurotrophic factor (BDNF) and gamma-aminobutyric acid (GABA) were measured at the same time points. The proteomic analysis was conducted to identify potentially vulnerable cellular and molecule targets of serum in the immediate post-exposure period.

在同一时间点测量血清多巴胺（DA），5-羟色胺（5-HT），脑源性神经营养因子（BDNF）和γ-氨基丁酸（GABA）。进行蛋白质组学分析以鉴定暴露后即刻血清中潜在的脆弱细胞和分子靶标。

Results revealed that: (1) Anxiety-like behavior increased significantly at 1 d post-exposure in the medium and high overpressure (90 kPa, 120 kPa) groups, returned to baseline at 7 days, and anxiety-like behavior in the high overpressure groups re-emerged at 28 d and 90 d. (2) High overpressure (120 kPa) impaired learning and memory in the immediate post-exposure period.

结果显示：（1）中等和高超压（90 kPa，120 kPa）组暴露后1 d焦虑样行为显着增加，在7天时恢复到基线，高超压组的焦虑样行为在28 d和90 d时再次出现。（2）高超压（120 kPa）在暴露后立即损害学习和记忆。

(3) The serum DA levels decreased significantly at 1 d post-exposure in the medium and high overpressure groups; The 5-HT levels decreased significantly at 1 d and 90 d in the high overpressure groups; The BDNF levels decreased significantly at 90 d in the high overpressure groups. (4) Proteomic analysis identified 38, 306, and 57 different.

（3） 中度和高超压组暴露后1天血清DA水平显着降低；高超压组在1 d和90 d时5-HT水平显着降低；在高超压组中，BDNF水平在90天时显着降低。（4） 蛋白质组学分析确定了38306和57个不同的。

Blast-induced traumatic brain injury (bTBI) is a significant medical and health concern in trauma surgery, both during peacetime and in wartime1. More than 20% of people working in explosion-related industries suffered a closed head injury as a result of blast overpressure (BOP) exposure, resulting in headaches, insomnia, anxiety, depression, memory and disorientation, placing a heavy burden on their families and society2,3.

爆炸引起的创伤性脑损伤（bTBI）是创伤手术中一个重要的医学和健康问题，无论是在和平时期还是在战争时期1。超过20%的爆炸相关行业工作人员因爆炸超压（BOP）暴露而遭受闭合性头部受伤，导致头痛，失眠，焦虑，抑郁，记忆力和定向障碍，给他们的家庭和社会带来沉重负担2,3。

Due to the mild brain injury symptoms being not obvious, it is easy to be missed or misdiagnosed, thus timely identification and proper managing of blast-induced brain trauma are critical since traumatic brain injuries (TBIs) often worsen in clinical outcome within 48 h if not identified timely or not treated appropriately4.Clinical reports have indicated the development of cognitive associated disorders following BOP exposure.

由于轻度脑损伤症状不明显，很容易被遗漏或误诊，因此及时识别和正确处理爆炸性脑损伤至关重要，因为创伤性脑损伤（TBI）如果不及时发现或不适当治疗，通常会在48小时内恶化临床结果4。临床报告表明，BOP暴露后认知相关疾病的发展。

The majority of these disorders are associated with anxiety, attention deficits, memory issues and impaired /altered problem solving skills3. Overlapping symptoms with other forms of trauma, such as non-blast related traumatic brain injury (TBI) and post-traumatic stress disorder (PTSD) have confounding effects on differential diagnosis.

这些疾病中的大多数与焦虑，注意力缺陷，记忆问题和解决问题的能力受损/改变有关3。与其他形式的创伤重叠的症状，例如非爆炸相关的创伤性脑损伤（TBI）和创伤后应激障碍（PTSD），对鉴别诊断有混杂的影响。

Animal models of shock wave injuries have been established to investigate injury mechanisms from overpressure exposure and its subsequent neurological impairments. Most published studies are limited to a single overpressure exposure or repeated exposures at the same magnitude of overpressure5,6,7,8,9,10.

已经建立了冲击波损伤的动物模型，以研究超压暴露及其随后的神经损伤的损伤机制。大多数已发表的研究仅限于单一超压暴露或重复暴露在相同程度的超压5,6,7,8,9,10。

Researchs11,12 employed a rodent model of primary blast neurotrauma to determine the pressure at which acute neurological alterations occurred, while information on the neurological behavior and serum molecular changes in response to varied levels of overpressure at chronic stage is still unk.

研究11,12采用原发性爆炸性神经创伤的啮齿动物模型来确定急性神经系统改变发生的压力，而关于慢性期不同超压水平下神经行为和血清分子变化的信息尚不清楚。

Shock Wave Overpressure simulated exposure

冲击波超压模拟暴露

After subtracting the baseline value, the three types of diaphragm rupture generated shock waves with the following overpressures as measured by the sensor: (65.3 ± 1.5) kPa, (91.7 ± 1.3) kPa, and (120.3 ± 10.5) kPa. The duration of the positive pressure was (4.4 ± 0.3) ms, (4.9 ± 0.7) ms and (6.3 ± 1.3) ms, respectively (Fig. 1).Fig.

减去基线值后，三种类型的隔膜破裂产生冲击波，传感器测量的超压如下：（65.3±1.5）kPa，（91.7±1.3）kPa和（120.3±10.5）kPa。正压持续时间分别为（4.4±0.3）ms，（4.9±0.7）ms和（6.3±1.3）ms（图1）。。

1The time-pressure profile of a shockwave recorded near the head of the rat. Schematic diagram of biological shock tube(A). 1. High pressure gas; 2. High voltage drive section; 3. Diaphragm; 4. Low voltage driven section; 5. Rat observation window; 6. Overpressure sensor. The arrow pointed in the direction of shock wave propagation.

1在大鼠头部附近记录的冲击波的时间-压力曲线。生物激波管示意图（A）。1、高压气体；2、高压驱动部分；3、隔膜；4、低压驱动段；5、大鼠观察窗；超压传感器。箭头指向冲击波传播的方向。

Shock wave simulated exposure in rats (B). Representative pressure profiles of low (60 kPa, C), moderate (90 kPa, D) and high (120 kPa, E) shock wave overpressure.Full size image.

。低（60 kPa，C）、中等（90 kPa，D）和高（120 kPa，E）冲击波超压的代表性压力剖面。全尺寸图像。

Moderate and High Levels Shock Wave Overpressure Exposure Rats Displayed Anxiety-Like Behavior at 1d post blast

中等和高水平冲击波超压暴露大鼠在爆炸后1d表现出焦虑样行为

Locomotor activity in light–dark box test and open field test was assessed to evaluate the anxiety-like behavior of rats. At 7 d post-blast, no significant differences were found in light–dark box test or open field test between the Sham group and the blast-injured groups (60 kPa, 90 kPa, and 120 kPa).

评估明暗盒测试和旷场测试中的运动活动，以评估大鼠的焦虑样行为。在爆炸后7天，假手术组和爆炸伤组（60 kPa，90 kPa和120 kPa）在明暗盒试验或旷场试验中未发现显着差异。

At 1 d, the 90 kPa and 120 kPa groups showed a significant decrease in number of visits and time spent in light in the light–dark box test compared to the Sham group (Fig. 2A, B and E, one-way ANOVA, F (3, 40) = 8.67, F (3, 36) = 8.39, p < 0.05). Similarly, distance traveled and number of visits in center in open field test were also comparable between the two groups (Fig. 2C, D and F, one-way ANOVA, F (3, 36) = 5.66, F (3, 36) = 4.04, p < 0.05).

在第1天，与假手术组相比，90 kPa和120 kPa组在明暗盒试验中的就诊次数和光照时间显着减少（图2A，B和E，单因素方差分析，F（3,40）=8.67，F（3,36）=8.39，p<0.05）。同样，两组在野外试验中的行进距离和中心访问次数也相当（图2C，D和F，单因素方差分析，F（3,36）=5.66，F（3,36）=4.04，p<0.05）。

At 28 d, the 120 kPa groups exhibited significantly decreased distance traveled and number of visits in center in open field test compared to the Sham group (Fig. 2C and D, p < 0.05). At 90 d, the 120 kPa groups exhibited significantly decreased all parameters compared to the Sham group (p < 0.05). Track plots showed that the 120 kPa group moved less in the light box and the center of open field than the Sham group at 1 d and 90 d after exposure (Fig. 2E and F).

在第28天，与假手术组相比，120 kPa组在野外试验中的行进距离和中心访问次数显着减少（图2C和d，p<0.05）。。轨迹图显示，在暴露后1天和90天，120 kPa组在灯箱和开阔场地中心的移动比假手术组少（图2E和F）。

These findings suggest that exposure to moderate and high intensities overpressure (90 kPa and 120 kPa), may induce anxiety-like behaviors in rats at an early stage. Over time, anxiety-like behaviors in the medium-intensity group were relieved, while behavioral abnormalities in the high-intensity re-emerged.Fig.

这些发现表明，暴露于中度和高强度超压（90 kPa和120 kPa）可能会在早期诱发大鼠的焦虑样行为。随着时间的推移，中等强度组的焦虑样行为得到缓解，而高强度组的行为异常再次出现。。

2Light-dark box and oped field experiment outcomes following Blast Exposure. Number of visits in light (A) and time spent in light (B) of rats in the light–dark box examination. Distance traveled in center (C) and number of visits in center (D) in open field exami.

2爆炸暴露后的明暗箱和oped现场实验结果。在明暗盒检查中，大鼠在光照（A）下的访问次数和在光照（B）下花费的时间。在野外exami中，中心（C）的行进距离和中心（D）的访问次数。

High Level Shock Wave Overpressure Exposure Rats Displayed inferior learning and memory at 1d post blast.Nondeclarative memory, which involves learning and retaining skills and habits without conscious recall, was assessed using an active avoidance training paradigm. At 1 d after exposure, interaction between number of active avoidance group and time, main group effect and main time effect were all significant (Fig. 3A, repeated measures ANOVA, F (9, 108) = 3.79, F (2.6, 94.3) = 239.40, F (3, 36) = 20.65, all p < 0.05).

高水平冲击波超压暴露大鼠在爆炸后1d表现出较差的学习和记忆能力。使用主动回避训练范式评估了非退化记忆，该记忆涉及学习和保留技能和习惯而无需有意识地回忆。暴露后1天，主动回避组数量与时间，主要组效应和主要时间效应之间的相互作用均显着（图3A，重复测量方差分析，F（9108）=3.79，F（2.6,94.3）=239.40，F（3,36）=20.65，均p<0.05）。

It is suggested that with the increase of training time, the ability of rats to avoid harmful stimuli in each group has a tendency to improve, but the improvement of the ability in all exposure groups is lower than Sham group. The simple effects within time analysis showed rats in the 120 kPa group had a significantly fewer times on the last training trial (p < 0.05), suggesting an impairment of memory formation.

提示随着训练时间的增加，各组大鼠避免有害刺激的能力有改善的趋势，但各暴露组的能力改善程度均低于假手术组。。

Interaction between active avoidance reaction time group and time was not significant (F (9, 108) = 0.08, p > 0.05). A probe test conducted on the 6th day further revealed a significant reduction in active avoidance times in the 120 kPa group compared to the Sham group (Fig. 3C, one-way ANOVA, F (3, 32) = 9.35, p < 0.05), indicating insufficient long-term memory storage after extensive training.

主动回避反应时间组与时间之间的相互作用不显着（F（9108）=0.08，p＞0.05）。第6天进行的探针测试进一步显示，与假手术组相比，120 kPa组的主动回避时间显着减少（图3C，单因素方差分析，F（3,32）=9.35，p < 0.05), 表明经过大量训练后长期记忆存储不足。

No significant differences in active avoidance times (Fig. 3E, G, I, K) and reaction time (Fig. 3B, D, F, H, J, L) were observed among the groups during other training trials or probe tests. These findings suggest that shock wave overpressure exposure, particularly at the 120 kPa level, may selectively impair the formation and consolidation of nondeclarative memories in rats.Fig.

在其他训练试验或探针测试期间，各组之间的主动回避时间（图3E，G，I，K）和反应时间（图3B，D，F，H，J，L）没有显着差异。这些发现表明，冲击波超压暴露，特别是在120 kPa水平，可能会选择性地损害大鼠非退化记忆的形成和巩固。。

3Active avoidance experiment outcomes following Blast Exposure. Active avoi.

3爆炸暴露后的主动回避实验结果。活跃avoi。

Data availability

数据可用性

Sequence data that support the findings of this study have been deposited in the iProX Integrated Proteome Resources with the primary accession code IPX0009707002. The Username and Password of iProX is Mning and 104248.

支持这项研究结果的序列数据已保存在iProX Integrated Proteome Resources中，主要登录号为IPX0009707002。iProX的用户名和密码是Mning和104248。

ReferencesChin, D. L. & Zeber, J. E. Mental Health Outcomes among Military Service members after severe Injury in Combat and TBI. Mil. Med. 185, 5–6 (2020).

参考文献Chin，D.L.＆Zeber，J.E。在战斗和TBI中严重受伤后军人的心理健康结果。医学185，5-6（2020）。

Google Scholar

谷歌学者

Tovar, M. A., Bell, R. S. & Neal, C. J. Epidemiology of Blast Neurotrauma: a Meta-analysis of Blast Injury patterns in the military and civilian populations. World Neurosurg. 146, 308–314 (2021).PubMed

Tovar，M.A.，Bell，R.S.＆Neal，C.J。爆炸性神经创伤的流行病学：军事和平民群体爆炸伤模式的荟萃分析。。PubMed出版社

Google Scholar

谷歌学者

Hussain, S. F. et al. Traumatic brain injury and sight loss in military and veteran populations- a review. Military Med. Res. 8, 42 (2021).

Hussain，S.F.等人，《军人和退伍军人的创伤性脑损伤和视力丧失-综述》。军事医学第8、42号决议（2021年）。

Google Scholar

谷歌学者

Hoyt, D. B. et al. ), and National Institute of Neurological Disorders and Stroke (NINDS) of the National Institutes of Health (NIH), and the Department of Defense (DOD). J. Trauma. 57, 410–415 (2004).PubMed

Hoyt，D.B.等人），美国国立卫生研究院（NIH）的国家神经疾病和中风研究所（NINDS）以及国防部（DOD）。J、 创伤。57410-415（2004）。PubMed出版社

Google Scholar

谷歌学者

Nonaka, M. et al. Behavioral and myelin-related abnormalities after Blast-Induced mild traumatic brain Injury in mice. J. Neurotrauma. 38, 1551–1571 (2021).PubMed

Nonaka，M.等人。小鼠爆炸性轻度创伤性脑损伤后的行为和髓鞘相关异常。J、 神经创伤。381551-1571（2021）。PubMed出版社

PubMed Central

公共医学中心

Google Scholar

谷歌学者

Smith, J. E. & Garner, J. Pathophysiology of primary blast injury. J. R. Army Med. Corps. 165, 57–62 (2019).PubMed

Smith，J.E。和Garner，J。原发性爆炸伤的病理生理学。J、 陆军医学兵团。165,57-62（2019）。PubMed出版社

Google Scholar

谷歌学者

Aravind, A. et al. Behavioral deficits in animal models of Blast Traumatic Brain Injury. Front. Neurol. 11, 990 (2020).PubMed

Aravind，A。等人。爆炸性创伤性脑损伤动物模型中的行为缺陷。正面。神经病学。11990（2020）。PubMed出版社

PubMed Central

公共医学中心

Google Scholar

谷歌学者

Murugan, M. et al. Chemokine signaling mediated monocyte infiltration affects anxiety-like behavior following blast injury. Brain. Behav. Immun. 88, 340–352 (2020).CAS

Murugan，M。等人。趋化因子信号传导介导的单核细胞浸润影响爆炸伤后的焦虑样行为。大脑。行为。免疫。88340–352（2020）。中科院

PubMed

PubMed

Google Scholar

谷歌学者

Chen, S. et al. Low-intensity blast induces acute glutamatergic hyperexcitability in mouse hippocampus leading to long-term learning deficits and altered expression of proteins involved in synaptic plasticity and serine protease inhibitors. Neurobiol. Dis. 165, 105634 (2022).CAS

Chen，S。等人。低强度blast诱导小鼠海马急性谷氨酸能过度兴奋，导致长期学习缺陷和突触可塑性和丝氨酸蛋白酶抑制剂相关蛋白表达的改变。神经生物学。Dis。165105634（2022）。中科院

PubMed

PubMed

Google Scholar

谷歌学者

Dickerson, M. R. et al. Glial activation in the Thalamus contributes to Vestibulomotor deficits following Blast-Induced Neurotrauma. Front. Neurol. 11, 618 (2020).PubMed

Dickerson，M.R。等人。丘脑中的神经胶质激活导致爆炸性神经创伤后的前庭运动缺陷。正面。神经病学。11618（2020）。PubMed出版社

PubMed Central

公共医学中心

Google Scholar

谷歌学者

Vandevord, P. J. et al. Mild neurotrauma indicates a range-specific pressure response to low level shock wave exposure. Ann. Biomed. Eng. 40, 227–236 (2012).Sajja, V. S. S. et al. Subacute oxidative stress and glial reactivity in the amygdala are associated with increased anxiety following blast neurotrauma.

Vandevord，P.J。等人。轻度神经创伤表明对低水平冲击波暴露的范围特异性压力反应。安。生物医学。工程40227-236（2012）。Sajja，V.S.S.等人。杏仁核中的亚急性氧化应激和神经胶质反应性与爆炸性神经创伤后焦虑增加有关。

Shock 44, 71 –78 (2015).Woolf, C. J. & Salter, M. W. Neuronal plasticity: increasing the gain in pain. Science 288, 1765–1769 (2000).Kozlova, Y. & Kozlov, S. Сhanges of trace elements in the cerebellum and their influence on the rats behavior in elevated plus maze in the acute period of mild blast-induced brain injury.

。Woolf，C.J。＆Salter，M.W。神经元可塑性：增加疼痛的增加。科学2881765-1769（2000）。Kozlova，Y。＆Kozlov，S。С小脑中微量元素的变化及其对轻度爆炸性脑损伤急性期高架十字迷宫大鼠行为的影响。

J. Trace Elem. Med. Biology: Organ. Soc. Minerals Trace Elem. (GMS). 78, 127189 (2023).CAS .

J、 跟踪元素。医学生物学：器官。社会矿物质微量元素。（GMS）。78127189（2023）。。

Google Scholar

谷歌学者

Li, Y. et al. Effect of early normobaric hyperoxia on Blast-Induced Traumatic Brain Injury in rats. Neurochem. Res. 45, 2723–2731 (2020).CAS

Li，Y。等。早期常压高氧对大鼠爆炸性创伤性脑损伤的影响。神经化学。第452723-2731号决议（2020年）。中科院

PubMed

PubMed

Google Scholar

谷歌学者

Schipper, P. et al. Prior fear conditioning does not impede enhanced active avoidance in serotonin transporter knockout rats. Behav. Brain. Res. 326, 77–86 (2017).CAS

Schipper，P。等人。先前的恐惧条件反射并不妨碍血清素转运蛋白敲除大鼠增强的主动回避。行为。大脑。第326、77-86号决议（2017年）。中科院

PubMed

PubMed

Google Scholar

谷歌学者

Sabariego, M. et al. Active avoidance learning differentially activates ERK phosphorylation in the primary auditory and visual cortices of roman high- and low-avoidance rats. Physiol. Behav. 201, 31–41 (2019).CAS

Sabariego，M。等人。主动回避学习差异地激活罗马高回避和低回避大鼠初级听觉和视觉皮层中的ERK磷酸化。生理学。行为。201,31-41（2019）。中科院

PubMed

PubMed

Google Scholar

谷歌学者

Corne, R. et al. Spontaneous resurgence of conditioned fear weeks after successful extinction in brain injured mice. Prog. Neuro-psychopharmacol. Biol. Psychiatry. 88, 276–286 (2019).CAS

Corne，R.等人。脑损伤小鼠成功灭绝数周后，条件性恐惧自发复活。程序。神经精神药理学。生物精神病学。88276-286（2019）。中科院

Google Scholar

谷歌学者

Perez Garcia, G. et al. Progressive cognitive and post-traumatic stress disorder-related behavioral traits in rats exposed to repetitive low-level blast. J. Neurotrauma. 38, 2030–2045 (2021).PubMed

Perez-Garcia，G.等人。暴露于重复性低水平爆炸的大鼠的进行性认知和创伤后应激障碍相关行为特征。J、 神经创伤。382030–2045（2021）。PubMed出版社

PubMed Central

公共医学中心

Google Scholar

谷歌学者

Perez-Garcia, G. et al. Chronic post-traumatic stress disorder-related traits in a rat model of low-level blast exposure. Behav. Brain. Res. 340, 117–125 (2018).PubMed

Perez-Garcia，G.等人。低水平爆炸暴露大鼠模型中的慢性创伤后应激障碍相关特征。行为。大脑。第340117-125号决议（2018年）。PubMed出版社

Google Scholar

谷歌学者

Perez-Garcia, G. et al. PTSD-Related behavioral traits in a rat model of Blast-Induced mTBI are reversed by the mGluR2/3 receptor antagonist BCI-838. eNeuro. 5, 0357-17 (2018).Conio, B. et al. Opposite effects of dopamine and serotonin on resting-state networks: review and implications for psychiatric disorders.

Perez-Garcia，G。等人。mGluR2/3受体拮抗剂BCI-838逆转了爆炸诱导的mTBI大鼠模型中PTSD相关的行为特征。埃纽罗。50357-17（2018）。多巴胺和血清素对静息状态网络的相反作用：综述和对精神疾病的影响。

Mol. Psychiatry. 25, 82–93 (2020).PubMed .

摩尔精神病学。25，82-93（2020）。PubMed。

Google Scholar

谷歌学者

Okaty, B. W., Commons, K. G. & Dymecki, S. M. Embracing diversity in the 5-HT neuronal system. Nat. Rev. Neurosci. 20, 397–424 (2019).CAS

Okaty，B.W.，Commons，K.G。＆Dymecki，S.M。拥抱5-HT神经元系统的多样性。神经科学杂志。20397-424（2019）。中科院

PubMed

PubMed

Google Scholar

谷歌学者

Beamer, M. et al. Primary blast injury causes cognitive impairments and hippocampal circuit alterations. Exp. Neurol. 283, 16–28 (2016).CAS

原发性爆炸伤会导致认知障碍和海马回路改变。实验神经学。283,16-28（2016）。中科院

PubMed

PubMed

PubMed Central

公共医学中心

Google Scholar

谷歌学者

Pourhamzeh, M. et al. The roles of Serotonin in Neuropsychiatric disorders. Cell. Mol. Neurobiol. 42, 1671–1692 (2022).CAS

Pourhamzeh，M.等人。血清素在神经精神疾病中的作用。细胞。分子神经生物学。421671-1692（2022）。中科院

PubMed

PubMed

Google Scholar

谷歌学者

De Deurwaerdère, P. & Di Giovanni, G. Serotonin in Health and Disease. Int. J. Mol. Sci. 21, 3500 (2020).PubMed

De Deurwardère，P。＆Di Giovanni，G。血清素在健康和疾病中的作用。Int.J.Mol.Sci。213500（2020）。PubMed出版社

PubMed Central

公共医学中心

Google Scholar

谷歌学者

Kourosh-Arami, M., Komaki, A. & Zarrindast, M. R. Dopamine as a potential target for learning and memory: contributing to related neurological disorders. CNS Neurol. Disord. Drug Targets. 22, 558–576 (2023).Fernandes, M. F., Lau, D., Sharma, S. & Fulton, S. Anxiety-like behavior in female mice is modulated by STAT3 signaling in midbrain dopamine neurons.

Kourosh Arami，M.，Komaki，A。＆Zarrindast，M.R。多巴胺作为学习和记忆的潜在靶标：导致相关的神经系统疾病。中枢神经系统神经学。混乱。药物靶标。22558-576（2023）。Fernandes，M.F.，Lau，D.，Sharma，S。＆Fulton，S。雌性小鼠的焦虑样行为受中脑多巴胺神经元中STAT3信号传导的调节。

Brain Behav. Immun. 95, 391–400 (2021).Tong, Q. et al. D1 receptor-expressing neurons in ventral tegmental area alleviate mouse anxiety-like behaviors via glutamatergic projection to lateral septum. Mol. Psychiatry. 28, 625–638 (2023).CAS .

大脑行为。免疫。95391-400（2021）。Tong，Q。等人。腹侧被盖区D1受体表达神经元通过谷氨酸能投射到外侧隔来缓解小鼠焦虑样行为。摩尔精神病学。28625-638（2023）。。

PubMed

PubMed

Google Scholar

谷歌学者

Vogrinc, D. et al. Genetic variability of incretin receptors affects the occurrence of neurodegenerative diseases and their characteristics. Heliyon. 10, e39157 (2024).CAS

Vogrinc，D。等人。肠促胰岛素受体的遗传变异影响神经退行性疾病的发生及其特征。海伦。10，e39157（2024）。中科院

PubMed

PubMed

PubMed Central

公共医学中心

Google Scholar

谷歌学者

La, Y. et al. Quantitative proteomic analysis reveals key proteins involved in Testicular Development of yaks. Int. J. Mol. Sci. 25, 8433 (2024).CAS

定量蛋白质组学分析揭示了牦牛睾丸发育的关键蛋白质。Int.J.Mol.Sci。258433（2024）。中科院

PubMed

PubMed

PubMed Central

公共医学中心

Google Scholar

谷歌学者

Sathoria, P. et al. Asprosin regulates male reproduction in teleosts: an in vitro study in Channa punctata. J. Endocrinol. 263, e240146 (2024).CAS

Sathoria，P。等人。Asprosin调节硬骨鱼的雄性生殖：一项在斑点蟾蜍中的体外研究。J、 内分泌。263，e240146（2024）。中科院

PubMed

PubMed

Google Scholar

谷歌学者

Gao, X. et al. Low-temperature-induced disruption of reproductive axis and sperm vitality via stress axis in Monopterus albus. Gen. Comp. Endocrinol. 359, 114617 (2024).CAS

Gao，X。等人。低温通过应激轴诱导黄鳝生殖轴和精子活力的破坏。总公司。内分泌。359114617（2024）。中科院

PubMed

PubMed

Google Scholar

谷歌学者

Mangini, L. et al. Galactokinase 1 is the source of elevated galactose-1pho -sphate and cerebrosides are modestly reduced in a mouse model of classic galactosemia. JIMD Rep. 65, 280–294 (2024).PubMed

Mangini，L。等人。半乳糖激酶1是半乳糖-1磷酸升高的来源，在经典半乳糖血症的小鼠模型中，脑苷脂适度减少。JIMD Rep.65280–294（2024）。PubMed出版社

PubMed Central

公共医学中心

Google Scholar

谷歌学者

Qiu, Y. et al. Liriodendrin stimulates proliferation and milk protein synthesis of mammary epithelial cells via the PI3K-DDX18 signaling. In vitro cellular & developmental biology. Animal 60, 949–958 (2024).CAS

Qiu，Y。等人。鹅掌楸素通过PI3K-DDX18信号传导刺激乳腺上皮细胞的增殖和乳蛋白合成。体外细胞与发育生物学。动物60949-958（2024）。中科院

Google Scholar

谷歌学者

Zhou, J. et al. Integrating whole-genome resequencing and RNA sequencing data reveals selective sweeps and differentially expressed genes related to nervous system changes in Luxi Gamecocks. Genes 14, 584 (2023).CAS

Zhou，J.等人整合了全基因组重测序和RNA测序数据，揭示了选择性扫描和与鲁西斗鸡神经系统变化相关的差异表达基因。基因14584（2023）。中科院

PubMed

PubMed

PubMed Central

公共医学中心

Google Scholar

谷歌学者

Gu, Y. et al. Up-regulation of RACGAP1 promotes progressions of hepatocellular carcinoma regulated by GABPA via PI3K/AKT pathway. Oxid. Med. Cell Longev. 2022, 3034150 (2022).Yang, X. et al. Overexpression of rac GTPase activating protein 1 contributes to proliferation of cancer cells by reducing hippo signaling to promote cytokinesis.

Gu，Y。等。RACGAP1的上调通过PI3K/AKT途径促进GABPA调节的肝细胞癌的进展。氧化剂。医学Cell Longev。。Yang，X。等人。rac GTPase激活蛋白1的过表达通过减少hippo信号传导促进胞质分裂来促进癌细胞的增殖。

Gastroenterology 155, 1233–1249e22 (2018).Zhao, W. M. & Fang, G. MgcRacGAP controls the assembly of the contractile ring and the initiation of cytokinesis. Proc. Natl. Acad. Sci. U.S.A. 102, 13158–13163 (2005).ADS .

胃肠病学1551233-1249e22（2018）。Zhao，W.M。＆Fang，G。MgcRacGAP控制收缩环的组装和胞质分裂的开始。程序。纳特尔。阿卡德。科学。U、 S.A.10213158–13163（2005）。广告。

CAS

中科院

PubMed

PubMed

PubMed Central

公共医学中心

Google Scholar

谷歌学者

Yamazaki, D., Kurisu, S. & Takenawa, T. Involvement of Rac and rho signaling in cancer cell motility in 3D substrates. Oncogene 28, 1570–1583 (2009).CAS

Yamazaki，D.，Kurisu，S。＆Takenawa，T。Rac和rho信号传导参与3D底物中癌细胞的运动。癌基因281570-1583（2009）。中科院

PubMed

PubMed

Google Scholar

谷歌学者

Soto-Heredero, G. et al. Glycolysis - a key player in the inflammatory response. FEBS J. 287, 3350–3369 (2020).CAS

Soto Herdero，G。等人。糖酵解-炎症反应的关键参与者。FEBS J.2873350–3369（2020）。中科院

PubMed

PubMed

PubMed Central

公共医学中心

Google Scholar

谷歌学者

Kanehisa, M. & Goto, S. KEGG: kyoto encyclopedia of genes and genomes. Nucleic Acids Res. 28, 27–30 (2000).CAS

Kanehisa，M。＆Goto，S。KEGG：京都基因与基因组百科全书。核酸研究28,27-30（2000）。中科院

PubMed

PubMed

PubMed Central

公共医学中心

Google Scholar

谷歌学者

Kanehisa, M. Toward understanding the origin and evolution of cellular organisms. Protein Sci. 28, 1947–1951 (2019).CAS

Kanehisa，M。了解细胞生物的起源和进化。蛋白质科学。281947-1951（2019）。中科院

PubMed

PubMed

PubMed Central

公共医学中心

Google Scholar

谷歌学者

Kanehisa, M., Furumichi, M., Sato, Y., Kawashima, M. & Ishiguro-Watanabe, M. KEGG for taxonomy-based analysis of pathways and genomes. Nucleic Acids Res. 51, D587–D592 (2023).CAS

Kanehisa，M.，Furumichi，M.，Sato，Y.，Kawashima，M。＆Ishiguro Watanabe，M。KEGG用于基于分类学的途径和基因组分析。核酸研究51，D587–D592（2023）。中科院

PubMed

PubMed

Google Scholar

谷歌学者

Guo, N. et al. PI3K/AKT signaling pathway: molecular mechanisms and therapeutic potential in depression. Pharmacol. Res. 206, 107300 (2024).CAS

。药理学。第206、107300（2024）号决议。中科院

PubMed

PubMed

Google Scholar

谷歌学者

Chu, E. et al. Dysregulated phosphoinositide 3-kinase signaling in microglia: shaping chronic neuroinflammation. J. Neuroinflamm. 18, 276 (2021).CAS

Chu，E.等人。小胶质细胞中磷酸肌醇3-激酶信号失调：塑造慢性神经炎症。J、 神经炎症。18276（2021）。中科院

Google Scholar

谷歌学者

Hsu, C. et al. 2-Ethylhexyl diphenyl phosphate aggravates colitis-induced neuroinflammation and behavioral abnormalities by inhibiting the PI3K-AKT-NF-κB and Wnt/GSK3β signaling pathways. Ecotoxicol. Environ. Saf. 286, 117173 (2024).CAS

Hsu，C。等人。2-乙基己基二苯基磷酸酯通过抑制PI3K-AKT-NF-κB和Wnt/GSK3β信号通路加重结肠炎诱导的神经炎症和行为异常。生态毒性。环境。南非。2861117173（2024）。中科院

PubMed

PubMed

Google Scholar

谷歌学者

Feldner, A. et al. Loss of Mpdz impairs ependymal cell integrity leading to perinatal-onset hydrocephalus in mice. EMBO Mol. Med. 9, 890–905 (2017).CAS

Feldner，A。等人，Mpdz的缺失会损害室管膜细胞的完整性，从而导致小鼠围产期发作性脑积水。EMBO Mol.Med.9890–905（2017）。中科院

PubMed

PubMed

PubMed Central

公共医学中心

Google Scholar

谷歌学者

González, A. et al. Glucose metabolism and AD: evidence for a potential diabetes type 3. Alzheimer’s Res. Therapy. 14, 1–11 (2022).

González，A.等人，《葡萄糖代谢和AD：潜在的3型糖尿病的证据》。阿尔茨海默病治疗。14，1-11（2022）。

Google Scholar

谷歌学者

Mason, S. Lactate shuttles in neuroenergetics-homeostasis, allostasis and beyond. Front. Neurosci. 11, 43 (2017).ADS

Mason，S。Lactate穿梭于神经能量稳态，同种异体稳态和其他领域。正面。神经科学。11,43（2017）。广告

PubMed

PubMed

PubMed Central

公共医学中心

Google Scholar

谷歌学者

Higginbotham, L. et al. Integrated proteomics reveals brain-based cerebrospinal fluid biomarkers in asymptomatic and symptomatic Alzheimer’s disease. Sci. Adv. 6, eaaz9360 (2020).Johnson, E. C. B. et al. Large-scale proteomic analysis of Alzheimer’s disease brain and cerebrospinal fluid reveals early changes in energy metabolism associated with microglia and astrocyte activation.

综合蛋白质组学揭示了无症状和有症状阿尔茨海默病中基于大脑的脑脊液生物标志物。科学。Adv.6，eaaz9360（2020）。Johnson，E.C.B.等人。阿尔茨海默病大脑和脑脊液的大规模蛋白质组学分析揭示了与小胶质细胞和星形胶质细胞活化相关的能量代谢的早期变化。

Nat. Med. 26, 769–780 (2020).CAS .

《自然医学》26769-780（2020）。。

PubMed

PubMed

PubMed Central

公共医学中心

Google Scholar

谷歌学者

Johnson, E. C. B. et al. Cerebrospinal fluid proteomics define the natural history of autosomal dominant Alzheimer’s disease. Nat. Med. 29, 1979–1988 (2023).CAS

Johnson，E.C.B.等人脑脊液蛋白质组学定义了常染色体显性阿尔茨海默病的自然史。《自然医学》291979-1988（2023）。中科院

PubMed

PubMed

PubMed Central

公共医学中心

Google Scholar

谷歌学者

Bai, D. et al. ALDOA maintains NLRP3 inflammasome activation by controlling AMPK activation. Autophagy 18, 1673–1693 (2022).CAS

Bai，D。等人，ALDOA通过控制AMPK活化来维持NLRP3炎性体活化。自噬181673-1693（2022）。中科院

PubMed

PubMed

Google Scholar

谷歌学者

Almeida, M. F. et al. Distinct and dementia-related synaptopathy in the hippocampus after military blast exposures. Brain Pathol. 31, e12936 (2021).Sawyer, T. W. et al. Primary blast causes delayed effects without cell death in shell-encased brain cell aggregates. J. Neurotrauma. 35, 174–186 (2018).PubMed .

Almeida，M.F.等人。军事爆炸暴露后海马中不同的和痴呆相关的突触病变。脑病理学。31，e12936（2021）。Sawyer，T.W。等人。原发性爆炸会导致延迟效应，而壳包裹的脑细胞聚集体不会导致细胞死亡。J、 神经创伤。35174-186（2018）。PubMed。

Google Scholar

谷歌学者

Murphy, E. K. et al. Explosive-driven double-blast exposure: molecular, histopathological, and behavioral consequences. Sci. Rep. 10, 17446 (2020).ADS

Murphy，E.K.等人，《爆炸驱动的双重爆炸暴露：分子，组织病理学和行为后果》。科学。代表1017446（2020）。广告

CAS

中科院

PubMed

PubMed

PubMed Central

公共医学中心

Google Scholar

谷歌学者

Download referencesFundingThis work was supported by the Natural Science Foundation of Shaanxi Province (Program No. 2023-JC-QN-0983, 2023-JC-YB-684). The funding agencies had no role in the design and conduct of the study; in the collection, analysis, and interpretation of the data; or in the preparation, review, or approval of the manuscript.Author informationAuthors and AffiliationsXi’an Key Laboratory of Toxicology and Biological Effects, Research Center for Toxicological and Biological Effects, Institute for Hygiene of Ordnance Industry, Xi’an, 710065, ChinaNing Ma, Hong Wang, Qing Lu, Xiaolin Fan, Liang Li, Qi Wang, Xiao Li, Boya Yu, Yuhao Zhang & Junhong GaoSchool of Public Health, Xi’an Jiaotong University Health Science Center, Xi’an, 710061, ChinaJinren LiuAuthorsNing MaView author publicationsYou can also search for this author in.

下载参考文献资助这项工作得到了陕西省自然科学基金（项目编号2023-JC-QN-09832023-JC-YB-684）的支持。资助机构在研究的设计和实施中没有任何作用；在数据的收集，分析和解释中；或在手稿的准备，审查或批准中。作者信息作者和单位西安兵器工业卫生研究所毒理学和生物效应研究中心西安毒理学和生物效应重点实验室，西安，710065，马宁，王红，陆青，范晓林，梁丽，王琦，小丽，余伯亚，张宇浩和高俊宏西安交通大学卫生科学中心公共卫生学院，西安，710061，刘金仁作者MaView作者出版物您也可以在中搜索这位作者。

PubMed Google ScholarHong WangView author publicationsYou can also search for this author in

PubMed Google ScholarHong WangView作者出版物您也可以在

PubMed Google ScholarQing LuView author publicationsYou can also search for this author in

PubMed Google ScholarQing LuView作者出版物您也可以在

PubMed Google ScholarJinren LiuView author publicationsYou can also search for this author in

PubMed Google ScholarJinren LiuView作者出版物您也可以在

PubMed Google ScholarXiaolin FanView author publicationsYou can also search for this author in

PubMed Google ScholarXiaolin FanView作者出版物您也可以在

PubMed Google ScholarLiang LiView author publicationsYou can also search for this author in

PubMed Google ScholarQi WangView author publicationsYou can also search for this author in

PubMed Google ScholarQi WangView作者出版物您也可以在

PubMed Google ScholarXiao LiView author publicationsYou can also search for this author in

PubMed Google ScholarXiao LiView作者出版物您也可以在

PubMed Google ScholarBoya YuView author publicationsYou can also search for this author in

PubMed Google ScholarBoya YuView作者出版物您也可以在

PubMed Google ScholarYuhao ZhangView author publicationsYou can also search for this author in

PubMed Google ScholarYuhao ZhangView作者出版物您也可以在

PubMed Google ScholarJunhong GaoView author publicationsYou can also search for this author in

PubMed谷歌学者JunHong GaoView作者出版物您也可以在

PubMed Google ScholarContributionsNM. Performed the study, Analyzed the data, Wrote the manuscript. HW. and JL. Proteome sequencing analysis. QL. and XF. Molecular indicators monitor and data collation. LL. and YZ. Behavioral experiments and data collation. QW., BY. and XL. Establishment of animal model.

PubMed谷歌学术贡献SNM。进行了研究，分析了数据，撰写了手稿。硬件。和JL。蛋白质组测序分析。QL.和XF。分子指标监测和数据整理。LL。和YZ。行为实验和数据整理。质量。，和XL。动物模型的建立。

JG. Designed and coordinated the study, Project administration.Corresponding authorCorrespondence to.

日本。设计并协调研究，项目管理。对应作者对应。

Junhong Gao.Ethics declarations

高俊红。道德宣言

Competing interests

相互竞争的利益

We have no conflicts of interest to declare.

我们没有利益冲突需要申报。

Ethics approval

道德认可

All methods were carried out in accordance with relevant guidelines and regulations. The protocols for all animal experiments were approved by the Animal Welfare Committee of Institute for Hygiene of Ordnance Industry, China.

所有方法均按照相关指南和规定进行。所有动物实验的方案均经中国兵器工业卫生研究所动物福利委员会批准。

Ethical Statement

道德声明

This study and included experimental procedures were approved by the institutional animal care and use committee of institute for hygiene of ordnance industry (approval no. IACUC202302). The study is reported in accordance with ARRIVE guidelines. All animal housing and experiments were conducted in strict accordance with the institutional guidelines for care and use of laboratory animals..

这项研究和包括的实验程序得到了军械工业卫生研究所机构动物护理和使用委员会的批准（批准号IACUC202302）。该研究是根据ARRIVE指南报告的。所有动物饲养和实验均严格按照实验动物护理和使用的机构指南进行。。

Additional informationPublisher’s noteSpringer Nature remains neutral with regard to jurisdictional claims in published maps and institutional affiliations.Electronic supplementary materialBelow is the link to the electronic supplementary material.Supplementary Material 1Supplementary Material 2Rights and permissions.

。电子补充材料流是指向电子补充材料的链接。补充材料1补充材料2权利和许可。

Open Access This article is licensed under a Creative Commons Attribution-NonCommercial-NoDerivatives 4.0 International License, which permits any non-commercial use, sharing, distribution and reproduction in any medium or format, as long as you give appropriate credit to the original author(s) and the source, provide a link to the Creative Commons licence, and indicate if you modified the licensed material.

开放获取本文是根据知识共享署名非商业性NoDerivatives 4.0国际许可证授权的，该许可证允许以任何媒介或格式进行任何非商业性使用，共享，分发和复制，只要您对原始作者和来源给予适当的信任，提供知识共享许可证的链接，并指出您是否修改了许可材料。

You do not have permission under this licence to share adapted material derived from this article or parts of it. The images or other third party material in this article are included in the article’s Creative Commons licence, unless indicated otherwise in a credit line to the material. If material is not included in the article’s Creative Commons licence and your intended use is not permitted by statutory regulation or exceeds the permitted use, you will need to obtain permission directly from the copyright holder.

根据本许可证，您无权共享源自本文或其部分的改编材料。本文中的图像或其他第三方材料包含在文章的知识共享许可证中，除非该材料的信用额度中另有说明。如果材料未包含在文章的知识共享许可证中，并且您的预期用途未被法律法规允许或超出允许的用途，则您需要直接获得版权所有者的许可。

To view a copy of this licence, visit http://creativecommons.org/licenses/by-nc-nd/4.0/..

要查看此许可证的副本，请访问http://creativecommons.org/licenses/by-nc-nd/4.0/..

Reprints and permissionsAbout this articleCite this articleMa, N., Wang, H., Lu, Q. et al. Temporal changes of neurobehavior in rats following varied blast magnitudes and screening of serum biomarkers in early stage of brain injury.

转载和许可本文引用本文Ma，N.，Wang，H.，Lu，Q。等人。不同冲击强度后大鼠神经行为的时间变化以及脑损伤早期血清生物标志物的筛选。

Sci Rep 14, 30023 (2024). https://doi.org/10.1038/s41598-024-81656-9Download citationReceived: 27 August 2024Accepted: 28 November 2024Published: 03 December 2024DOI: https://doi.org/10.1038/s41598-024-81656-9Share this articleAnyone you share the following link with will be able to read this content:Get shareable linkSorry, a shareable link is not currently available for this article.Copy to clipboard.

科学报告1430023（2024）。https://doi.org/10.1038/s41598-024-81656-9Downloadhttps://doi.org/10.1038/s41598-024-81656-9Share本文与您共享以下链接的任何人都可以阅读此内容：获取可共享链接对不起，本文目前没有可共享的链接。复制到剪贴板。

Provided by the Springer Nature SharedIt content-sharing initiative

由Springer Nature SharedIt内容共享计划提供

KeywordsBlast waveBrain injuryAnxiety-like behaviorProteomics.

关键词冲击波脑损伤和类似焦虑的行为蛋白质组学。