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

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.

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).

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<0.0001). 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 distance 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.

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.