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中华神经创伤外科电子杂志 ›› 2025, Vol. 11 ›› Issue (03) : 137 -143. doi: 10.3877/cma.j.issn.2095-9141.2025.03.001

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靶向创伤性颅脑损伤神经炎症的药物治疗研究进展
刘羽阳, 封亚平()   
  1. 650032 昆明,解放军联勤保障部队第九二〇医院神经外科
  • 收稿日期:2024-03-15 出版日期:2025-06-15
  • 通信作者: 封亚平

Research progress in drug therapy targeting neuroinflammation in traumatic brain injury

Yuyang Liu, Yaping Feng()   

  1. Department of Neurosurgery, 920th Hospital of Joint Logistics Support Force, Kunming 650032, China
  • Received:2024-03-15 Published:2025-06-15
  • Corresponding author: Yaping Feng
引用本文:

刘羽阳, 封亚平. 靶向创伤性颅脑损伤神经炎症的药物治疗研究进展[J/OL]. 中华神经创伤外科电子杂志, 2025, 11(03): 137-143.

Yuyang Liu, Yaping Feng. Research progress in drug therapy targeting neuroinflammation in traumatic brain injury[J/OL]. Chinese Journal of Neurotraumatic Surgery(Electronic Edition), 2025, 11(03): 137-143.

创伤性颅脑损伤(TBI)是导致年轻人残疾和死亡的主要原因之一,可造成身体、心理和认知功能的急性或永久性损害。目前TBI的治疗以手术减压和对症支持治疗为主,尚缺乏针对病理机制的有效干预手段。近年来研究证实神经炎症在TBI的病理生理过程中发挥着关键作用,而靶向神经炎症的策略有望为TBI的治疗开辟新路径。本文主要讨论TBI神经炎症药物治疗的研究进展,以期为后续研究提供参考。

Traumatic brain injury (TBI) is one of the leading causes of disability and death among young people, resulting in acute or permanent damage to physical, psychological, and cognitive functions. Currently, the treatment for TBI primarily involves surgical decompression and symptomatic supportive care, with a lack of effective interventions targeting the underlying pathological mechanisms. Recent studies have confirmed that neuroinflammation plays a crucial role in the pathophysiological process of TBI, and strategies targeting neuroinflammation hold promise for providing new pathways for TBI. This review aims to discuss the progress in drug therapies targeting neuroinflammation in TBI, with the goal of providing reference for future research.

[1]
Jassam YN, Izzy S, Whalen M, et al. Neuroimmunology of traumatic brain injury: time for a paradigm shift[J]. Neuron, 2017, 95(6): 1246-1265. DOI: 10.1016/j.neuron.2017.07.010.
[2]
Bergold PJ. Treatment of traumatic brain injury with anti-inflammatory drugs[J]. Exp Neurol, 2016, 275(Pt 3): 367-380. DOI: 10.1016/j.expneurol.2015.05.024.
[3]
Haan BJ, Blackmon SN, Cobb AM, et al. Corticosteroids in critically ill patients: a narrative review[J]. Pharmacotherapy, 2024, 44(7): 581-602. DOI: 10.1002/phar.2944.
[4]
El-Saber Batiha G, Al-Gareeb AI, Saad HM, et al. COVID-19 and corticosteroids: a narrative review[J]. Inflammopharmacology, 2022, 30(4): 1189-1205. DOI: 10.1007/s10787-022-00987-z.
[5]
Kalra S, Malik R, Singh G, et al. Pathogenesis and management of traumatic brain injury(TBI): role of neuroinflammation and anti-inflammatory drugs[J]. Inflammopharmacology, 2022, 30(4): 1153-1166. DOI: 10.1007/s10787-022-01017-8.
[6]
Visser J, van Boxel-Dezaire A, Methorst D, et al. Differential regulation of interleukin-10(IL-10) and IL-12 by glucocorticoids in vitro[J]. Blood, 1998, 91(11): 4255-4264.
[7]
Girgis H, Palmier B, Croci N, et al. Effects of selective and non-selective cyclooxygenase inhibition against neurological deficit and brain oedema following closed head injury in mice[J]. Brain Res, 2013, 1491: 78-87. DOI: 10.1016/j.brainres.2012.10.049.
[8]
Wang J, Hou Y, Zhang L, et al. Estrogen attenuates traumatic brain injury by inhibiting the activation of microglia and astrocyte-mediated neuroinflammatory responses[J]. Mol Neurobiol, 2021, 58(3): 1052-1061. DOI: 10.1007/s12035-020-02171-2.
[9]
Farahani F, Khaksari M, Amiresmaili S, et al. Possible involvement of female sex steroid hormones in intracellular signal transduction mediated by cytokines following traumatic brain injury[J]. Brain Res Bull, 2022, 178: 108-119. DOI: 10.1016/j.brainresbull.2021.11.013.
[10]
Chen G, Shi J, Jin W, et al. Progesterone administration modulates TLRs/NF-kappaB signaling pathway in rat brain after cortical contusion[J]. Ann Clin Lab Sci, 2008, 38(1): 65-74.
[11]
Sen AP, Gulati A. Use of magnesium in traumatic brain injury[J]. Neurotherapeutics, 2010, 7(1): 91-99. DOI: 10.1016/j.nurt.2009.10.014.
[12]
Li W, Bai YA, Li YJ, et al. Magnesium sulfate for acute traumatic brain injury[J]. J Craniofac Surg, 2015, 26(2): 393-398. DOI: 10.1097/scs.0000000000001339.
[13]
Wang R, He M, Xu J. Initial serum magnesium level is associated with mortality risk in traumatic brain injury patients[J]. Nutrients, 2022, 14(19): 4174. DOI: 10.3390/nu14194174.
[14]
Scrimgeour AG, Carrigan CT, Condlin ML, et al. Dietary zinc modulates matrix metalloproteinases in traumatic brain injury[J]. J Neurotrauma, 2018, 35(20): 2495-2506. DOI: 10.1089/neu.2017.5614.
[15]
Hellmich HL, Eidson KA, Capra BA, et al. Injured fluoro-jade-positive hippocampal neurons contain high levels of zinc after traumatic brain injury[J]. Brain Res, 2007, 1127(1): 119-126. DOI: 10.1016/j.brainres.2006.09.094.
[16]
中国血脂管理指南修订联合专家委员会.中国血脂管理指南(2023年)[J].中国循环杂志, 2023, 38(3): 237-271. DOI: 10.3969/j.issn.1000-3614.2023.03.001.
[17]
Wible EF, Laskowitz DT. Statins in traumatic brain injury[J]. Neurotherapeutics, 2010, 7(1): 62-73. DOI: 10.1016/j.nurt.2009.11.003.
[18]
吴蕾,张少兰,李浩诣,等.他汀类药物对创伤性颅脑损伤患者病死率及神经功能预后影响的荟萃分析[J].中华医学杂志, 2022, 102(11): 813-820. DOI: 10.3760/cma.j.cn112137-20210626-01449.
[19]
Xu X, Gao W, Cheng S, et al. Anti-inflammatory and immunomodulatory mechanisms of atorvastatin in a murine model of traumatic brain injury[J]. J Neuroinflammation, 2017, 14(1): 167. DOI: 10.1186/s12974-017-0934-2.
[20]
中华医学会创伤学分会创伤感染学组,中华医学会急诊医学分会创伤学组.创伤后抗菌药物预防性使用专家共识[J].中华创伤杂志, 2016, 32(10): 865-869. DOI: 10.3760/cma.j.issn.1001-8050.2016.10.001.
[21]
Meythaler J, Fath J, Fuerst D, et al. Safety and feasibility of minocycline in treatment of acute traumatic brain injury[J]. Brain Inj, 2019, 33(5): 679-689. DOI: 10.1080/02699052.2019.1566968.
[22]
Bergold PJ, Furhang R, Lawless S. Treating traumatic brain injury with minocycline[J]. Neurotherapeutics, 2023, 20(6): 1546-1564. DOI: 10.1007/s13311-023-01426-9.
[23]
Sangobowale M, Nikulina E, Bergold PJ. Minocycline plus N-acetylcysteine protect oligodendrocytes when first dosed 12 hours after closed head injury in mice[J]. Neurosci Lett, 2018, 682: 16-20. DOI: 10.1016/j.neulet.2018.06.010.
[24]
中华医学会儿科学分会临床药理学组,国家儿童健康与疾病临床医学研究中心,中华医学会儿科学分会呼吸学组合理用药协作组,等.儿童常见呼吸系统疾病免疫调节剂合理使用专家共识(2024年版)[J].中国实用儿科杂志, 2024, 39(11): 801-809. DOI: 10.19538/j.ek2024110601.
[25]
Kilbaugh TJ, Bhandare S, Lorom DH, et al. Cyclosporin A preserves mitochondrial function after traumatic brain injury in the immature rat and piglet[J]. J Neurotrauma, 2011, 28(5): 763-774. DOI: 10.1089/neu.2010.1635.
[26]
Hansson MJ, Elmér E. Cyclosporine as therapy for traumatic brain injury[J]. Neurotherapeutics, 2023, 20(6): 1482-1495. DOI: 10.1007/s13311-023-01414-z.
[27]
Brines ML, Ghezzi P, Keenan S, et al. Erythropoietin crosses the blood-brain barrier to protect against experimental brain injury[J]. Proc Natl Acad Sci USA, 2000, 97(19): 10526-10531. DOI: 10.1073/pnas.97.19.10526.
[28]
Peng W, Xing Z, Yang J, et al. The efficacy of erythropoietin in treating experimental traumatic brain injury: a systematic review of controlled trials in animal models[J]. J Neurosurg, 2014, 121(3): 653-664. DOI: 10.3171/2014.6.Jns132577.
[29]
国家心血管病专家委员会心血管代谢医学专业委员会. Omega-3脂肪酸在心血管疾病防治中的作用中国专家共识[J].中国循环杂志, 2023, 38(2): 116-130. DOI: 10.3969/j.issn.1000-3614.2023.02.002.
[30]
Chen X, Chen C, Fan S, et al. Omega-3 polyunsaturated fatty acid attenuates the inflammatory response by modulating microglia polarization through SIRT1-mediated deacetylation of the HMGB1/NF-κB pathway following experimental traumatic brain injury[J]. J Neuroinflammation, 2018, 15(1): 116. DOI: 10.1186/s12974-018-1151-3.
[31]
陈伟. 2016《维生素制剂临床应用专家共识》解读及再喂养综合征的防治[J].中华老年医学杂志, 2017, 36(3): 242-244. DOI: 10.3760/cma.j.issn.0254-9026.2017.03.004.
[32]
Lee JM, Jeong SW, Kim MY, et al. The effect of vitamin D supplementation in patients with acute traumatic brain injury[J]. World Neurosurg, 2019, 126: e1421-e1426. DOI: 10.1016/j.wneu.2019.02.244.
[33]
Tang H, Hua F, Wang J, et al. Progesterone and vitamin D combination therapy modulates inflammatory response after traumatic brain injury[J]. Brain Inj, 2015, 29(10): 1165-1174. DOI: 10.3109/02699052.2015.1035330.
[34]
Barbre AB, Hoane MR. Magnesium and riboflavin combination therapy following cortical contusion injury in the rat[J]. Brain Res Bull, 2006, 69(6): 639-646. DOI: 10.1016/j.brainresbull.2006.03.009.
[35]
Smith AC, Holden RC, Rasmussen SM, et al. Effects of nicotinamide on spatial memory and inflammation after juvenile traumatic brain injury[J]. Behav Brain Res, 2019, 364: 123-132. DOI: 10.1016/j.bbr.2019.02.024.
[36]
Chen W, Man X, Zhang Y, et al. Medial prefrontal cortex oxytocin mitigates epilepsy and cognitive impairments induced by traumatic brain injury through reducing neuroinflammation in mice[J]. Sci Rep, 2023, 13(1): 5214. DOI: 10.1038/s41598-023-32351-8.
[37]
Mairesse J, Zinni M, Pansiot J, et al. Oxytocin receptor agonist reduces perinatal brain damage by targeting microglia[J]. Glia, 2019, 67(2): 345-359. DOI: 10.1002/glia.23546.
[38]
Osier N, McGreevy E, Pham L, et al. Melatonin as a therapy for traumatic brain injury: a review of published evidence[J]. Int J Mol Sci, 2018, 19(5): 1539. DOI: 10.3390/ijms19051539.
[39]
Wang J, Jiang C, Zhang K, et al. Melatonin receptor activation provides cerebral protection after traumatic brain injury by mitigating oxidative stress and inflammation via the Nrf2 signaling pathway[J]. Free Radic Biol Med, 2019, 131: 345-355. DOI: 10.1016/j.freeradbiomed.2018.12.014.
[40]
Ding K, Wang H, Xu J, et al. Melatonin stimulates antioxidant enzymes and reduces oxidative stress in experimental traumatic brain injury: the Nrf2-ARE signaling pathway as a potential mechanism[J]. Free Radic Biol Med, 2014, 73: 1-11. DOI: 10.1016/j.freeradbiomed.2014.04.031.
[41]
Yang SH, Gangidine M, Pritts TA, et al. Interleukin 6 mediates neuroinflammation and motor coordination deficits after mild traumatic brain injury and brief hypoxia in mice[J]. Shock, 2013, 40(6): 471-475. DOI: 10.1097/shk.0000000000000037.
[42]
Clark IA, Vissel B. Broader insights into understanding tumor necrosis factor and neurodegenerative disease pathogenesis infer new therapeutic approaches[J]. J Alzheimers Dis, 2021, 79(3): 931-948. DOI: 10.3233/jad-201186.
[43]
Okuma Y, Wake H, Teshigawara K, et al. Anti-high mobility group box 1 antibody therapy may prevent cognitive dysfunction after traumatic brain injury[J]. World Neurosurg, 2019, 122: e864-e871. DOI: 10.1016/j.wneu.2018.10.164.
[44]
张泽瀚,陶丙岩,张鼎,等.体外细胞模型实验探讨钠钾氯同向转运体对血脑屏障渗透性的调控机制[J].解放军医学院学报, 2022, 43(5): 586-594. DOI: 10.3969/j.issn.2095-5227.2022.05.017.
[45]
Liu X, Zhao Z, Ji R, et al. Inhibition of P2X7 receptors improves outcomes after traumatic brain injury in rats[J]. Purinergic Signal, 2017, 13(4): 529-544. DOI: 10.1007/s11302-017-9579-y.
[46]
陶丙岩,刘羽阳,裴洁,等.嘌呤能离子通道型受体7对小鼠创伤性脑损伤后神经炎症及脑水肿的影响[J].解放军医学院学报, 2023, 44(4): 359-364. DOI: 10.3969/j.issn.2095-5227.2023.04.008.
[47]
Wallisch JS, Simon DW, Bayır H, et al. Cerebrospinal fluid NLRP3 is increased after severe traumatic brain injury in infants and children[J]. Neurocrit Care, 2017, 27(1): 44-50. DOI: 10.1007/s12028-017-0378-7.
[48]
Ismael S, Nasoohi S, Ishrat T. MCC950, the selective inhibitor of nucleotide oligomerization domain-like receptor protein-3 inflammasome, protects mice against traumatic brain injury[J]. J Neurotrauma, 2018, 35(11): 1294-1303. DOI: 10.1089/neu.2017.5344.
[49]
Zhang LM, Xin Y, Wu ZY, et al. STING mediates neuroinflammatory response by activating NLRP3-related pyroptosis in severe traumatic brain injury[J]. J Neurochem, 2022, 162(5): 444-462. DOI: 10.1111/jnc.15678.
[50]
Ge X, Li W, Huang S, et al. The pathological role of NLRs and AIM2 inflammasome-mediated pyroptosis in damaged blood-brain barrier after traumatic brain injury[J]. Brain Res, 2018, 1697: 10-20. DOI: 10.1016/j.brainres.2018.06.008.
[51]
Yang X, Chen L, Pu J, et al. Guideline of clinical neurorestorative treatment for brain trauma (2022 China version)[J]. J Neurorestoratology, 2022, 10(2): 100005. DOI: 10.1016/j.jnrt.2022.100005.
[52]
Caplan HW, Prabhakara KS, Toledano Furman NE, et al. Combination therapy with Treg and mesenchymal stromal cells enhances potency and attenuation of inflammation after traumatic brain injury compared to monotherapy[J]. Stem Cells, 2021, 39(3): 358-370. DOI: 10.1002/stem.3320
[53]
Wen L, Wang YD, Shen DF, et al. Exosomes derived from bone marrow mesenchymal stem cells inhibit neuroinflammation after traumatic brain injury[J]. Neural Regen Res, 2022, 17(12): 2717-2724. DOI: 10.4103/1673-5374.339489.
[54]
Zhong L, Wang J, Wang P, et al. Neural stem cell-derived exosomes and regeneration: cell-free therapeutic strategies for traumatic brain injury[J]. Stem Cell Res Ther, 2023, 14(1): 198. DOI: 10.1186/s13287-023-03409-1.
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