爆炸创伤性脑损伤相关精神障碍的 药物治疗进展
Advances in Pharmacological Treatment of Mental Disorders Associated with Blast-Induced Traumatic Brain Injury
DOI: 10.12677/acm.2026.163812, PDF,    科研立项经费支持
作者: 马锦萱, 王 鸿, 范小琳, 李 亮, 高俊宏*：兵器工业卫生研究所生物效应技术研究室，陕西 西安
关键词: 爆炸创伤性脑损伤；精神障碍；治疗药物；Blast-Induced Traumatic Brain Injury； Mental Disorders； Therapeutic Drugs
摘要: 爆炸冲击波性脑损伤(bTBI)是战时最常见的脑损伤类型，常导致人格改变、情绪困扰及认知功能下降等精神健康问题，不仅干扰病情的准确评估，还降低患者的治疗依从性。目前bTBI相关精神障碍的治疗仍以对症为主，因此亟需关注其预防和治疗策略。本文旨在综述bTBI所致精神障碍的治疗药物最新进展，以期为临床诊断和治疗提供参考和指导。
Abstract: Blast-induced traumatic brain injury (bTBI) is the most common type of brain injury during wartime, often leading to mental health issues such as personality changes, emotional distress, and cognitive decline. These complications not only interfere with accurate assessment of the condition but also reduce patients’ treatment compliance. Current therapeutic approaches for bTBI-related mental disorders remain primarily symptom-based, highlighting an urgent need to focus on prevention and treatment strategies. This article aims to review the latest advances in pharmacological treatments for mental disorders caused by bTBI, with the goal of providing reference and guidance for clinical diagnosis and management.
文章引用：马锦萱, 王鸿, 范小琳, 李亮, 高俊宏. 爆炸创伤性脑损伤相关精神障碍的 药物治疗进展[J]. 临床医学进展, 2026, 16(3): 467-472. https://doi.org/10.12677/acm.2026.163812

参考文献

[1] Baker, T.L., Agoston, D.V., Brady, R.D., Major, B., McDonald, S.J., Mychasiuk, R., et al. (2021) Targeting the Cerebrovascular System: Next-Generation Biomarkers and Treatment for Mild Traumatic Brain Injury. The Neuroscientist, 28, 594-612. [Google Scholar] [CrossRef] [PubMed]
[2] Das, M., Mohapatra, S. and Mohapatra, S.S. (2012) New Perspectives on Central and Peripheral Immune Responses to Acute Traumatic Brain Injury. Journal of Neuroinflammation, 9, Article No. 236. [Google Scholar] [CrossRef] [PubMed]
[3] 罗兰兰, 柴艳, 江荣才, 等. 脑创伤康复期抑郁障碍的特征及治疗[J]. 天津医药, 2013, 41(8): 812-813.
[4] 陶平宇, 祝一虹. 回院认知功能训练对脑外伤所致精神障碍出院患者认知障碍的疗效观察[J]. 护理与康复, 2017, 16(10): 1092-1093.
[5] 董强利, 叶兰仙, 张玉堂. 创伤后应激障碍的影响因素及心理危机干预[J]. 精神医学杂志, 2012, 25(1): 72-74.
[6] 梁喜安. 重型颅脑损伤后精神障碍的发生率、表现形式及影响因素分析[J]. 中外医学研究, 2015, 13(14): 53-55.
[7] Jackson, W.T. and Starling, A.J. (2019) Concussion Evaluation and Management. Medical Clinics of North America, 103, 251-261. [Google Scholar] [CrossRef] [PubMed]
[8] Brouard, J.T., Schweimer, J.V., Houlton, R., Burnham, K.E., Quérée, P. and Sharp, T. (2015) Pharmacological Evidence for 5-HT6 Receptor Modulation of 5-HT Neuron Firing in Vivo. ACS Chemical Neuroscience, 6, 1241-1247. [Google Scholar] [CrossRef] [PubMed]
[9] Fan, X., Wang, H., Lv, X., Wang, Q., Yu, B., Li, X., et al. (2025) The pCREB/BDNF Pathway in the Hippocampus Is Involved in the Therapeutic Effect of Selective 5-HT Reuptake Inhibitors in Adult Male Rats Exposed to Blast Traumatic Brain Injury. Brain Sciences, 15, Article No. 236. [Google Scholar] [CrossRef] [PubMed]
[10] Berretta, A., Tzeng, Y. and Clarkson, A.N. (2014) Post-Stroke Recovery: The Role of Activity-Dependent Release of Brain-Derived Neurotrophic Factor. Expert Review of Neurotherapeutics, 14, 1335-1344. [Google Scholar] [CrossRef] [PubMed]
[11] Sofroniew, M.V., Howe, C.L. and Mobley, W.C. (2001) Nerve Growth Factor Signaling, Neuroprotection, and Neural Repair. Annual Review of Neuroscience, 24, 1217-1281. [Google Scholar] [CrossRef] [PubMed]
[12] Pereira, C.A., Rodrigues, F.L., Ruginsk, S.G., Zanotto, C.Z., Rodrigues, J.A., Duarte, D.A., et al. (2017) Chronic Treatment with Fluoxetine Modulates Vascular Adrenergic Responses by Inhibition of Pre-and Post-Synaptic Mechanisms. European Journal of Pharmacology, 800, 70-80. [Google Scholar] [CrossRef] [PubMed]
[13] Zanos, P., Moaddel, R., Morris, P.J., Riggs, L.M., Highland, J.N., Georgiou, P., et al. (2018) Ketamine and Ketamine Metabolite Pharmacology: Insights into Therapeutic Mechanisms. Pharmacological Reviews, 70, 621-660. [Google Scholar] [CrossRef] [PubMed]
[14] Zhang, X., Zhao, Y., Du, Y., Sun, H., Zhang, W., Wang, A., et al. (2021) Effect of Ketamine on Mood Dysfunction and Spatial Cognition Deficits in PTSD Mouse Models via HCN1-BDNF Signaling. Journal of Affective Disorders, 286, 248-258. [Google Scholar] [CrossRef] [PubMed]
[15] Riggs, L.M., Aracava, Y., Zanos, P., Fischell, J., Albuquerque, E.X., Pereira, E.F.R., et al. (2019) (2R,6R)-Hydroxynorketamine Rapidly Potentiates Hippocampal Glutamatergic Transmission through a Synapse-Specific Presynaptic Mechanism. Neuropsychopharmacology, 45, 426-436. [Google Scholar] [CrossRef] [PubMed]
[16] Zarate, C.A., Brutsche, N., Laje, G., Luckenbaugh, D.A., Venkata, S.L.V., Ramamoorthy, A., et al. (2012) Relationship of Ketamine’s Plasma Metabolites with Response, Diagnosis, and Side Effects in Major Depression. Biological Psychiatry, 72, 331-338. [Google Scholar] [CrossRef] [PubMed]
[17] Highland, J.N., Morris, P.J., Zanos, P., Lovett, J., Ghosh, S., Wang, A.Q., et al. (2018) Mouse, Rat, and Dog Bioavailability and Mouse Oral Antidepressant Efficacy of (2R,6R)-Hydroxynorketamine. Journal of Psychopharmacology, 33, 12-24. [Google Scholar] [CrossRef] [PubMed]
[18] Zanos, P. and Gould, T.D. (2018) Mechanisms of Ketamine Action as an Antidepressant. Molecular Psychiatry, 23, 801-811. [Google Scholar] [CrossRef] [PubMed]
[19] Diering, G.H. and Huganir, R.L. (2018) The AMPA Receptor Code of Synaptic Plasticity. Neuron, 100, 314-329. [Google Scholar] [CrossRef] [PubMed]
[20] Guo, R., Li, H., Li, X., Xue, Z., Sun, Y., Ma, D., et al. (2018) Downregulation of Neuroligin1 Ameliorates Postoperative Pain through Inhibiting Neuroligin1/Postsynaptic Density 95-Mediated Synaptic Targeting of Α-Amino-3-Hydroxy-5-Methyl-4-Isoxazole Propionate Receptor Glua1 Subunits in Rat Dorsal Horns. Molecular Pain, 14, 174-186. [Google Scholar] [CrossRef] [PubMed]
[21] Zhou, M., Liu, Z., Yu, J., Li, S., Tang, M., Zeng, L., et al. (2018) Quantitative Proteomic Analysis Reveals Synaptic Dysfunction in the Amygdala of Rats Susceptible to Chronic Mild Stress. Neuroscience, 376, 24-39. [Google Scholar] [CrossRef] [PubMed]
[22] Zanos, P., Highland, J.N., Stewart, B.W., Georgiou, P., Jenne, C.E., Lovett, J., et al. (2019) (2R,6R)-Hydroxynorketamine Exerts mGlu2 Receptor-Dependent Antidepressant Actions. Proceedings of the National Academy of Sciences, 116, 6441-6450. [Google Scholar] [CrossRef] [PubMed]
[23] Garcia, G.P., Perez, G.M., Gasperi, R.D., Sosa, M.A.G., Otero-Pagan, A., Abutarboush, R., et al. (2023) (2R,6R)-Hydroxynorketamine Treatment of Rats Exposed to Repetitive Low-Level Blast Injury. Neurotrauma Reports, 4, 197-217. [Google Scholar] [CrossRef] [PubMed]
[24] 刘荣辉, 张博, 李宁, 等. 通窍活血汤联合小剂量氯丙嗪治疗颅脑额叶损伤后精神躁狂发作的临床研究[J]. 辽宁中医杂志, 2014, 41(12): 2602-2603.
[25] Lee, H., Lee, Y., Chung, C., Park, S., Shin, H.J., Joe, E., et al. (2024) The Antipsychotic Chlorpromazine Reduces Neuroinflammation by Inhibiting Microglial Voltage‐Gated Potassium Channels. Glia, 73, 210-227. [Google Scholar] [CrossRef] [PubMed]
[26] Wu, J., Li, A., Li, Y., Li, X., Zhang, Q., Song, W., et al. (2016) Chlorpromazine Inhibits Mitochondrial Apoptotic Pathway via Increasing Expression of Tissue Factor. The International Journal of Biochemistry & Cell Biology, 70, 82-91. [Google Scholar] [CrossRef] [PubMed]
[27] Li, H., Zhang, Y., Zhou, L., Han, F., Wang, M., Xue, M., et al. (2014) Chlorpromazine Confers Neuroprotection against Brain Ischemia by Activating BKCa Channel. European Journal of Pharmacology, 735, 38-43. [Google Scholar] [CrossRef] [PubMed]
[28] Leonhardt, R. and Berger, R.G. (2014) Nootkatone. In: Schrader, J. and Bohlmann, J., Eds., Advances in Biochemical Engineering/Biotechnology, Springer International Publishing, 391-404. [Google Scholar] [CrossRef] [PubMed]
[29] He, B., Xu, F., Xiao, F., Yan, T., Wu, B., Bi, K., et al. (2017) Neuroprotective Effects of Nootkatone from Alpiniae Oxyphyllae Fructus against Amyloid-β-Induced Cognitive Impairment. Metabolic Brain Disease, 33, 251-259. [Google Scholar] [CrossRef] [PubMed]
[30] Park, J., Park, J., Leem, Y., Kim, D. and Kim, H. (2021) NQO1 Mediates the Anti-Inflammatory Effects of Nootkatone in Lipopolysaccharide-Induced Neuroinflammation by Modulating the AMPK Signaling Pathway. Free Radical Biology and Medicine, 164, 354-368. [Google Scholar] [CrossRef] [PubMed]
[31] 王凯新, 王三旺, 翟庆龄, 等. 诺卡酮对抑郁样行为和海马中PKA/CREB/BDNF信号通路的影响[J]. 安徽医科大学学报, 2022, 57(5): 725-730.
[32] 范小琳, 王鸿, 王琪, 等. 诺卡酮对轻度脑爆震伤大鼠抑郁样行为的缓解作用及其机制[J]. 解放军医学杂志, 2024, 49(6): 694-700.
[33] Yan, T., Li, F., Xiong, W., Wu, B., Xiao, F., He, B., et al. (2020) Nootkatone Improves Anxiety‐ and Depression‐Like Behavior by Targeting Hyperammonemia‐Induced Oxidative Stress in D‐Galactosamine Model of Liver Injury. Environmental Toxicology, 36, 694-706. [Google Scholar] [CrossRef] [PubMed]
[34] Park, J., Leem, Y., Park, J., Kim, S. and Kim, H. (2023) Astrocytic Nrf2 Mediates the Neuroprotective and Anti-Inflammatory Effects of Nootkatone in an MPTP-Induced Parkinson’s Disease Mouse Model. Antioxidants, 12, Article No. 1999. [Google Scholar] [CrossRef] [PubMed]

为你推荐