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陆军军医大学(第三军医大学)军事预防医学系军队劳动卫生学教研室,教育部电磁辐射医学防护重点实验室,重庆
高鹏,E-mail:gaopeng999666@126.com
收稿:2026-06-02,
修回:2026-09-03,
录用:2026-09-04,
纸质出版:2026-10-30
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张文娟,邓平,王徽,等.头颈部高压脉冲电流暴露致小鼠急性神经行为异常且伴随海马可逆性损伤及转录组改变[J].陆军军医大学学报,2026,48(20):2849-2861.DOI:10.16016/j.2097-0927.202606007.
Zhang W J,Deng P,Wang H,et al.Acute neurobehavioral abnormalities induced by high-voltage pulsed current exposure to the head and neck in mice accompanied by reversible hippocampal injury and transcriptomic alterations[J].J Army Med Univ,2026,48(20):2849-2861.DOI:10.16016/j.2097-0927.202606007.
张文娟,邓平,王徽,等.头颈部高压脉冲电流暴露致小鼠急性神经行为异常且伴随海马可逆性损伤及转录组改变[J].陆军军医大学学报,2026,48(20):2849-2861.DOI:10.16016/j.2097-0927.202606007. DOI:
Zhang W J,Deng P,Wang H,et al.Acute neurobehavioral abnormalities induced by high-voltage pulsed current exposure to the head and neck in mice accompanied by reversible hippocampal injury and transcriptomic alterations[J].J Army Med Univ,2026,48(20):2849-2861.DOI:10.16016/j.2097-0927.202606007. DOI:
目的
2
电击可引起神经系统功能异常,但不同暴露部位所致急性神经行为异常的差异尚不清楚。本研究旨在比较头颈部、胸腹部及背部短时高压脉冲电流暴露对小鼠神经行为的影响,并基于海马转录组学探讨头颈部暴露诱发异常反应的潜在机制,为电击致神经系统损伤的风险评估提供实验依据。
方法
2
6~8周龄SPF级雄性C57BL/6J小鼠,体质量约20 g,采用随机数字表法分为(
n
=10):对照组、头颈部暴露组、胸腹部暴露组和背部暴露组。暴露组小鼠于麻醉状态下接受相应部位高压脉冲电流暴露5 s,对照组给予同等时长声光刺激(其余操作与暴露组相同)。暴露结束后立即行惊厥评分和强直时间评估,麻醉苏醒2 h后进行步态分析。基于上述结果,对头颈部暴露组和对照组行旷场实验、明暗箱实验及高架十字迷宫实验,以评估自主活动与焦虑样行为。取海马行HE及尼氏染色以观察神经组织病理改变,并行海马神经递质组学检测及RNA-seq分析,测定神经递质含量、筛选差异表达基因。
结果
2
与对照组相比,头颈部暴露组、胸腹部暴露组和背部暴露组均出现不同程度惊厥反应及步态异常,其中头颈部暴露组10只小鼠中有4只达到3级,6只达到4级;胸腹部暴露组10只小鼠中,1只达到3级;背部暴露组10只小鼠中,1只达到3级,1只达到4级;且头颈部暴露组强直持续时间明显长于胸腹部暴露组和背部暴露组(
P
<
0.000 1)。头颈部高压脉冲电流暴露后,小鼠表现出短暂的焦虑样行为,具体表现为暴露后2.5 h、26.0 h和50.0 h进入开臂次数减少、开臂停留时间缩短,暴露后2.5 h和26.0 h旷场中心区停留时间减少、总运动距离降低、明箱探索次数减少及明箱停留时间减少(
P
<
0.05)。随着时间延长,上述行为学异常逐渐恢复,至74.0 h时与对照组小鼠相比差异无统计学意义。海马形态学观察结果显示,头颈部暴露组CA1区和DG区神经元间隙增宽、尼氏体凝集及核固缩细胞数量增多(
P
<
0.05)。神经递质组学结果显示,头颈部暴露组海马5-羟色胺和甲状腺激素水平明显升高(
P
<
0.05),其余与急性应激相关的神经递质,如肾上腺素、多巴胺、谷氨酸、乙酰胆碱及组胺等未见明显异常。RNA-seq分析共鉴定出差异表达基因186个,其中上调93个、下调93个,主要富集于黏着斑、细胞外基质-受体相互作用、cGMP-PKG和PI3K-Akt等信号通路。
结论
2
相较于胸腹部和背部,头颈部短时高压脉冲电流暴露更易引发急性神经行为异常。头颈部短时高压脉冲电流暴露可造成小鼠海马可逆性损伤,伴随组织结构与基因转录水平的异常改变,可作为电击致神经系统损伤风险评估的重要实验参考。
Objective
2
Electric shock may cause neurological dysfunction
but the differences in acute neurobehavioral abnormalities induced by exposure to different body regions remain unclear. This study aimed to compare the effects of brief high-voltage pulsed current (HVPC) exposure to the head and neck
chest and abdomen
and back on neurobehavior in mice
and to explore the potential mechanism underlying the abnormal responses induced by head/neck exposure based on hippocampal transcriptomics
so as to provide an experimental basis for risk assessment of electrical shock-induced neurological damage.
Methods
2
Male SPF C57BL/6J mice (6 to 8 week old
weighing approximately 20 g) were randomly divided into 4 groups (
n
=10): control group
head/neck exposure group
chest/belly exposure group and back exposure group. Mice in the exposure groups were subjected to HVPC exposure at corresponding body regions for 5 s under anesthesia
while those in the control group received acoustic and light stimulation for same duration (with all other procedures identical to those of exposure groups). Seizure scores and tonic duration were assessed immediately after exposure
and gait analysis was performed at 2 h after anesthesia recovery. Based on the above results
open-field test
light-dark box test and elevated plus maze test were conducted in the head/neck exposure group and the control group to evaluate spontaneous locomotor activity and anxiety-like behaviors. Hippocampal tissues were harvested for HE and Nissl staining to examine neuropathological changes. Hippocampal neurotransmitter profiling and RNA-seq analysis were performed to detect neurotransmitter concentrations and screen differentially expressed genes (DEGs).
Results
2
Compared with the control group
the 3 exposure groups exhibited varying degrees of seizure responses and gait abnormalities. In the head/neck exposure group
4 of 10 mice had seizure reaching grade 3 and 6 reaching grade 4; in the chest/belly exposure group
1 mouse reached seizure grade 3; in the back exposure group
1 mouse reached grade 3 and 1 reached grade 4. The tonic duration was significantly longer in the head/neck exposure group than the chest/belly and back exposure groups (
P
<
0.000 1). After head/neck HVPC exposure
the mice demonstrated transient anxiety-like behaviors
manifested as decreased open-arm entry frequency and reduced open-arm residence time at 2.5
26.0
and 50.0 h after exposure
decreased central zone residence time and total travel dista
nce in the open-field test
as well as decreased entry frequency and residence time in the light compartment of light-dark box test at 2.5 and 26.0 h after exposure (
P
<
0.05). These behavioral abnormalities gradually recovered over time
and no significant differences were observed relative to the control group at 74.0 h post-exposure. Morphological observation of the hippocampus found more widened neuronal gaps
condensed Nissl bodies and increased counts of karyopyknotic neurons in the CA1 and DG regions in the head/neck exposure group (
P
<
0.05). Neurotransmitter profiling showed significantly elevated hippocampal 5-hydroxytryptamine and thyroid hormone levels (
P
<
0.05)
whereas no remarkable alterations in other acute stress-related neurotransmitters
such as epinephrine
dopamine
glutamate
acetylcholine and histamine in the head/neck exposure group. RNA-seq analysis identified a total of 186 DEGs
including 93 upregulated and 93 downregulated
which were mainly enriched in signaling pathways such as focal adhesion
extracellular matrix-receptor interaction
cGMP-PKG
and PI3K-Akt.
Conclusion
2
Compared with brief HVPC exposure to the chest and abdomen and the back
exposure to the head and neck is more likely to induce acute neurobehavioral abnormalities. Such exposure can cause reversible hippocampal injury in mice
accompanied by abnormal changes in tissue structure and gene transcription levels
and may serve as an important experimental reference for the risk assessment of nervous system injury induced by electric shock.
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