PDF(4802 KB)
PDF(4802 KB)
PDF(4802 KB)
创伤性颅脑损伤中神经功能障碍与认知功能损伤的动态变化
邹成功* 冯浩 陈兵 唐辉 邵川 孙谋 杨荣 何家全
Research on the dynamic changes of neurological dysfunction and cognitive function impairment in traumatic brain injury
ZOU Cheng-gong* FENG Hao CHEN Bing TANG Hui SHAO Chuan SUN Mou YANG Rong HE Jia-quan
目的 探讨创伤性颅脑损伤（TBI）模型小鼠神经功能与认知功能的动态变化及其机制。 方法 60只12月龄Balb/c小鼠，分为对照组（10只）与TBI模型组（50只），根据模型构建时间将TBI模型小鼠分组为，模型1d组、3d组、7d组、14d组和28d组，共5个亚组，每组10只。实验第29天分别开展神经功能评分，跳台测试。测完后处死取材，用于免疫组织化学、炎性细胞因子含量、Western blotting检测。 结果 与对照组相比，模型组小鼠各个时期神经功能评分明显增加，在第7天达到峰值后降低。然而，各个时期，模型组小鼠跳台错误潜伏期低于对照组，跳台错误次数高于对照组，且没有明显变化。此外，与对照组相比，模型组小鼠各个阶段离子化钙结合适配分子1（IBA1）、趋化因子C-X3-C基元配体1（CX3CL1）、CX3C趋化因子受体1（CX3CR1）、NOD样受体热蛋白结构域相关蛋白3（NLRP3）、磷酸化核因子（p-NF）-κB表达明显增加，在第7天达到峰值，之后开始降低。与此同时，炎性细胞因子白细胞介素6（IL-6）与肿瘤坏死因子α（TNF-α）含量先升高达到峰值，随后开始降低。然而，与对照组相比，模型组小鼠各个时期β淀粉样蛋白（Aβ）、p-Tau蛋白表达持续增加。 结论 TBI致模型鼠小胶质细胞持续活化，与炎症反应一同先升高，再降低，导致小鼠神经功能评分到达峰值后降低。此外，炎症反应可能作为Aβ沉积与Tau蛋白磷酸化的启动子，导致小鼠认知功能损伤。
Objective To explore the dynamic changes and mechanisms of neurological and cognitive functions in mice with traumatic brain injury (TBI). Methods Totally 60 12-month-old Balb/c mice were divided into control group (10 in group) and TBI group (50 in group).TBT model mice were divided into 5 subgroups according to the time of model construction, including model 1 day, model 1 day, model 3 day, model 7 day, model 14 days and model 28 days group with 10 in each group. At the 29th day of the experiment, neurological scores and step down tests were carried out. After the test, the mice were sacrificed for brains which were detected by immunohistochemistry staining, inflammatory cytokine tests and Western blotting. Results Compared with the control group, the neurological scores of mice in TBI group increased, and then decreased after the 7th day when the scores reached the peak. However, the latency of step down errors was lower than control group, and the number of step down errors was higher than control group which had no changes. Compared with the control group, the expression of lonized calcium-binding adapter molecule 1(IBA1), chemokine C-X3-C-motif ligand1(CX3CL1), C-X3-C chemokine receptor 1(CX3CR1), NOD-like receptor thermal protein domain associated protein 3(NLRP3), and phosphorylation nuclear factor(p-NF)-κB in TBI group increased and reached to the peak at the 7th day, and then started to decrease. At the same time, the levels of inflammatory cytokines interleukin-6(IL-6) and tumor necrosis factor-α(TNF-α) first increased to the peak, and then began to decrease. However, compared with the control group, the expression of amyloid β(Aβ) protein and p-Tau protein in the model group continued to increase at all time. Conclusion The TBI model caused continuous activation of microglia along with inflammatory response, which first increased and then decreased, resultsing in neurological scores changes. In addition, the inflammatory response may act as a promoter of Aβ protein deposition and Tau protein phosphorylation, leading to cognitive impairment in mice.
创伤性颅脑损伤
Traumatic brain injury / Neurological dysfunction / Cognitive function / Inflammation / Western blotting / Mouse
[1] Zhang Y, Xue Q, Song XY, et al. The therapeutic effect and mechanism of chitosan encapsulated human umbilical cord mesenchymal stem cells on traumatic brain injury in rats ［J］. Acta Anatomica Sinica, 2021,52 (2): 205-209. （in Chinese）
张宇,薛茜,宋笑雨,等. 壳聚糖包载人脐带间充质干细胞对创伤性脑损伤大鼠的治疗作用及机制［J］. 解剖学报,2021,52(2):205-209.
［2］Zhang YB, Wang JQ, Chen LX, et al. The value of brain injury index in the prognosis evaluation of coma patients with severe brain injury ［J］.
Chinese Journal of New Clinical Medicine, 2017, 10 (2): 117-120. （in Chinese）
张艺滨, 王建群, 陈良鑫, 等. 脑损伤指数在重型颅脑损伤昏迷患者预后评估中的价值［J］.中国临床新医学, 2017, 10(2): 117-120.
［3］Kim WS, Lee K, Kim S, et al. Transcranial direct current stimulation for the treatment of motor impairment following traumatic brain injury［J］. J Neuroeng Rehabil, 2019, 16(1): 14.
［4］Ikram M, Park HY, Ali T, et al. Melatonin as a potential regulator of oxidative stress, and neuroinflammation: mechanisms and implications for the management of brain injury-induced neurodegeneration［J］. J Inflamm Res, 2021, 14:6251-6264.
［5］Jiang J, Dai C, Niu X, et al. Establishment of a precise novel brain trauma model in a large animal based on injury of the cerebral motor cortex［J］. J Neurosci Methods, 2018, 307: 95-105.
［6］ 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.
［7］Var SR, Shetty AV, Grande AW, et al. Microglia and macrophages in neuroprotection, neurogenesis, and emerging therapies for stroke［J］. Cells, 2021, 10(12): 3555.
［8］McKee CA, Lukens JR. Emerging roles for the immune system in traumatic brain injury［J］. Front Immunol, 2016, 7: 556.
［9］Li T, Huang HY, Wang H, et al. Restoration of brain angiotensin-converting enzyme 2 alleviates neurological deficits after severe traumatic brain injury via mitigation of pyroptosis and apoptosis［J］. J Neurotrauma, 2021, 39(5-6):423-434.
［10］Zhao J, Wang Y, Wang D, et al. MiR-124-3p attenuates brain microvascular endothelial cell injury in vitro by promoting autophagy［J］. Histol Histopathol, 2022, 37(2): 159-168.
［11］Doroshenko ER, Drohomyrecky PC, Gower A, et al. Peroxisome proliferator-activated receptor-δ deficiency in microglia results in exacerbated axonal injury and tissue loss in experimental autoimmune encephalomyelitis［J］. Front Immunol, 2021, 12: 570425.
［12］Basilico B,Ferrucci L,Ratano P,et al. Microglia control glutamatergic synapses in the adult mouse hippocampus［J］. Glia, 2022, 70(1): 173-195.
［13］Thelin EP,Tajsic T,Zeiler FA,et al. Monitoring the neuroinflammatory response following acute brain injury［J］. Front Neurol, 2017, 8: 351.
［14］Zhi X, Zhang Y, Sun S, et al. NLRP3 inflammasome activation by foot-and-mouth disease virus infection mainly induced by viral RNA and non-structural protein 2B［J］. RNA Biol, 2020, 17(3): 335-349.
［15］Lian F, Cao C, Deng F, et al. Propofol alleviates postoperative cognitive dysfunction by inhibiting inflammation via up-regulating miR-223-3p in aged rats［J］. Cytokine, 2021, 150: 155783.
［16］Balseanu AT, Grigore M, Pinosanu LR, et al. Electric stimulation of neurogenesis improves behavioral recovery after focal ischemia in aged rats［J］. Front Neurosci, 2020, 14: 732.
［17］Dhami M, Raj K, Singh S. Neuroprotective effect of fucoxanthin against intracerebroventricular streptozotocin (ICV-STZ) induced cognitive impairment in experimental rats［J］. Curr Alzheimer Res, 2021, 18(8): 623-637.
PDF(4802 KB)
/
| 〈 |
|
〉 |
