Mild traumatic brain injury (mTBI)-induced post-traumatic headache (PTH) is a pressing public health concern and leading cause of disability worldwide. Although PTH is often accompanied by neurological disorders, the exact underlying mechanism remains largely unknown. Identifying potential biomarkers may prompt the diagnosis and development of effective treatments for mTBI-induced PTH. In this study, a mouse model of mTBI-induced PTH was established to investigate its effects on cerebral structure and function during short-term recovery. Results indicated that mice with mTBI-induced PTH exhibited balance deficits during the early post-injury stage. Metabolic kinetics revealed that variations in neurotransmitters were most prominent in the cerebellum, temporal lobe/cortex, and hippocampal regions during the early stages of PTH. Additionally, variations in brain functional activities and connectivity were further detected in the early stage of PTH, particularly in the cerebellum and temporal cortex, suggesting that these regions play central roles in the mechanism underlying PTH. Moreover, our results suggested that GABA and glutamate may serve as potential diagnostic or prognostic biomarkers for PTH. Future studies should explore the specific neural circuits involved in the regulation of PTH by the cerebellum and temporal cortex, with these two regions potentially utilized as targets for non-invasive stimulation in future clinical treatment.
轻度创伤性脑损伤(mTBI)引起的创伤后头痛(PTH)是一个紧迫的公共卫生问题，仍然是世界范围内致残的主要原因。创伤后头痛通常伴有神经系统疾病，然而，在很大程度上其确切的潜在机制仍然是未知的。识别潜在的生物标志物可以促进mTBI诱导的创伤后头痛的诊断和开发有效的治疗方法。该研究建立了mTBI诱导的创伤后头痛小鼠模型，并采用一系列技术研究mTBI在短时间恢复期内对大脑结构和功能的影响。结果表明，mTBI诱导的创伤后头痛在损伤后早期表现出平衡缺陷。代谢动力学研究显示，创伤后头痛早期神经递质的变化在小脑、颞叶皮层和海马区域最为突出。此外，在创伤后头痛早期，在大脑中进一步检测到功能活动和连通性的变化，特别是在小脑和颞叶皮层。上述结果表明，小脑和颞叶皮层在创伤后头痛机制的研究中起核心作用。此外，结果还表明，GABA和谷氨酸可能作为创伤后头痛的潜在诊断或预后生物标志物。未来的研究应探讨小脑和颞叶皮层参与创伤后头痛调节的特定神经回路，这两个区域可作为未来临床治疗中无创刺激治疗技术的靶点。.
Keywords: Cerebellum; Metabolic kinetics; Mild traumatic brain injury (mTBI); Post-traumatic headache (PTH); fMRI.