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研究生:洪國峯
研究生(外文):Kuo-Feng Hung
論文名稱:於大鼠模式中探討重複創傷性腦損傷之神經行為變化
論文名稱(外文):The Studies of Neurobehavioral Changes after Repetitive Traumatic Brain Injury in Rats
指導教授:楊維中楊維中引用關係
指導教授(外文):Wei-Chung Yang
口試委員:謝宗勳王家儀李怡萱
口試委員(外文):Tsung-Hsun HsiehJia-Yi WangI-Chuan Li
口試日期:2017-01-18
學位類別:碩士
校院名稱:臺北醫學大學
系所名稱:臨床藥物基因體學暨蛋白質體學碩士學位學程
學門:醫藥衛生學門
學類:醫學學類
論文種類:學術論文
論文出版年:2017
畢業學年度:105
語文別:中文
論文頁數:58
中文關鍵詞:腦創傷動物模型動物行為測試
外文關鍵詞:traumatic brain injuryanimal modelanimal behavior test
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創傷性腦損傷(Traumatic brain injury)在世界各地都是一項重要的公共衛生議題,尤其輕度腦損傷(Mild Traumatic brain injury, mTBI )患者,佔神經外傷人數高達80%,而其中又以重複輕度腦損傷(Repetitive mild traumatic brain injury, rmTBI)為主,研究指出有些患者腦部會產生過度磷酸化的tau蛋白、散佈型的星狀細胞及小神經膠質細胞增生和慢性神經元退化等慢性創傷腦病變(chronic traumatic encephalopathy, CTE)症狀,造成壽命減短及神經退化疾病的發生率上升,但是長久以來還是沒有客觀的診斷標準,進而造成無法有效診斷與治療。本實驗使用9週齡雄性Sprague-Dawley(SD)大鼠,隨機分成兩組,分別為控制組(僅吸入和撞擊組相同氣麻量)以及不同撞擊重量之重複輕度腦損傷組(給予重複相同程度的撞擊力道) (Repetitive mild traumatic brain injury)。之後藉由六項包括運動、感覺行為及認知測試,評估大鼠受傷程度與行為認知功能受損的關聯性,在結果上可以看到在不同嚴重程度的大鼠動物模型中發現,受傷越嚴重的動物對於平衡能力、神經學分數以及認知功能上的表現也越差。由於臨床收案,需要長時間的觀察與測試,才能明顯看出是否有行為及認知功能退化,本研究以實驗動物模型分析重複腦創傷後其受傷程度及行為、認知功能的關聯性。希望可以藉由建立好的動物模型來模擬人類腦部受傷後的情形,並且試著找出有效的診斷標的,進而提早預防以及治療。
Traumatic brain injury all over the world is an important public health issue, especially mild traumatic brain injury (mTBI). It is up to 80% in neurotrauma, especially repetitive mild traumatic brain injury (rmTBI) and another problem is chronic traumatic encephalopathy (CTE). Researchers pointed out that hyperphosphorylation of the tau protein, spreading astrocyte and microglial cell hyperplasia and chronic neuron degeneration etc. in some rmTBI patients the brain, that might reduce the lifespan and increase the neuron degenerative disease rate; however, diagnosis is still lacking and current treatment is also not very effective. In this studies, we used nine-week-old male Sprague-Dawley (SD) rats, which were randomly divided into two groups, as the control group (only Gas anesthesia treated) and the treatment group (rmTBI) by weight drop impact. Six tests were carried out for behavioral and cognitive tests to assess the degree of injury associated with the degradation of the behavioral and cognitive functions. In results, the gradations in impact pressure produced progressive degrees of injury severity in the balance function, neurological score as well as cognitive function. The test model of a rmTBI animal, which mimics the repetitive TBI patient’s injured conditions, may allow to follow the long-term observations and to develop an effective diagnosis, prevention, and treatment of behavioral and cognitive dysfunction.
中文摘要 1
Abstract 3
第一章 研究背景 4
壹、重複創傷性腦損傷 4
一、 創傷性腦損傷簡介 4
二、 重複創傷性腦損傷 4
貳、創傷性腦損傷動物模型 6
一、 液柱撞擊損傷(fluid percussion injury, FPI) 6
二、 可控制皮質撞擊損傷(controlled cortical Impact, CCI) 6
三、 爆炸損傷(blast injury) 7
四、落錘撞擊損傷(weight drop impact, WDI)動物模型 7
第二章 研究動機與目的 10
第三章 實驗材料與方法 11
壹、實驗材料 11
一、 動物實驗流程 11
二、 實驗動物 14
三、 重複創傷性腦損傷動物模型材料 15
貳、實驗方法 17
一、 重複創傷性腦損傷模型 17
二、 神經行為評估量表 20
三、 平衡木測試 22
四、 貼紙移除試驗 23
五、 新奇事物認知測試 24
六、 統計分析 25
第四章 實驗結果 26
壹、不同嚴重程度的大鼠體重變化 26
貳、不同嚴重程度的大鼠神經行為評估量表 26
參、不同嚴重程度的大鼠平衡木測試 26
肆、不同嚴重程度的大鼠貼紙移除試驗 26
伍、不同嚴重程度的大鼠新奇事物認知測試 27
第五章 討論 38
第六章 結論 42
第七章 未來研究方向 43
第八章 參考文獻 44
[1] H. Alaranta, S. Koskinen, L. Leppanen, H. Palomaki, Nationwide epidemiology of hospitalized patients with first-time traumatic brain injury with special reference to prevention, Wien Med Wochenschr, 150 (2000) 444-448.
[2] F. Tagliaferri, C. Compagnone, M. Korsic, F. Servadei, J. Kraus, A systematic review of brain injury epidemiology in Europe, Acta Neurochir (Wien), 148 (2006) 255-268; discussion 268.
[3] J.H. Yi, A.S. Hazell, Excitotoxic mechanisms and the role of astrocytic glutamate transporters in traumatic brain injury, Neurochem Int, 48 (2006) 394-403.
[4] M.C. Morganti-Kossmann, M. Rancan, P.F. Stahel, T. Kossmann, Inflammatory response in acute traumatic brain injury: a double-edged sword, Curr Opin Crit Care, 8 (2002) 101-105.
[5] O. Farkas, J.T. Povlishock, Cellular and subcellular change evoked by diffuse traumatic brain injury: a complex web of change extending far beyond focal damage, Prog Brain Res, 161 (2007) 43-59.
[6] P.M. Lenzlinger, M.C. Morganti-Kossmann, H.L. Laurer, T.K. McIntosh, The duality of the inflammatory response to traumatic brain injury, Mol Neurobiol, 24 (2001) 169-181.
[7] N. Marklund, L. Hillered, Animal modelling of traumatic brain injury in preclinical drug development: where do we go from here?, British Journal of Pharmacology, 164 (2011).
[8] J. Ghajar, Traumatic brain injury, The Lancet, 356 (2000) 923-929.
[9] J.A. Langlois, W. Rutland-Brown, M.M. Wald, The epidemiology and impact of traumatic brain injury: a brief overview, J Head Trauma Rehabil, 21 (2006) 375-378.
[10] J.F. Kraus, P. Nourjah, The epidemiology of mild, uncomplicated brain injury, J Trauma, 28 (1988) 1637-1643.
[11] T. Tanaka, Y. Takano, S. Tanaka, N. Hironaka, K. Kobayashi, T. Hanakawa, K. Watanabe, M. Honda, Transcranial direct-current stimulation increases extracellular dopamine levels in the rat striatum, Front Syst Neurosci, 7 (2013) 6.
[12] K.G. Harmon, J.A. Drezner, M. Gammons, K.M. Guskiewicz, M. Halstead, S.A. Herring, J.S. Kutcher, A. Pana, M. Putukian, W.O. Roberts, American Medical Society for Sports Medicine position statement: concussion in sport, Br J Sports Med, 47 (2013) 15-26.
[13] C.C. Giza, J.S. Kutcher, S. Ashwal, J. Barth, T.S. Getchius, G.A. Gioia, G.S. Gronseth, K. Guskiewicz, S. Mandel, G. Manley, D.B. McKeag, D.J. Thurman, R. Zafonte, Summary of evidence-based guideline update: evaluation and management of concussion in sports: report of the Guideline Development Subcommittee of the American Academy of Neurology, Neurology, 80 (2013) 2250-2257.
[14] P. McCrory, W.H. Meeuwisse, M. Aubry, B. Cantu, J. Dvorak, R.J. Echemendia, L. Engebretsen, K. Johnston, J.S. Kutcher, M. Raftery, A. Sills, B.W. Benson, G.A. Davis, R.G. Ellenbogen, K. Guskiewicz, S.A. Herring, G.L. Iverson, B.D. Jordan, J. Kissick, M. McCrea, A.S. McIntosh, D. Maddocks, M. Makdissi, L. Purcell, M. Putukian, K. Schneider, C.H. Tator, M. Turner, Consensus statement on concussion in sport: the 4th International Conference on Concussion in Sport held in Zurich, November 2012, Br J Sports Med, 47 (2013) 250-258.
[15] K. Eakin, Y. Li, Y.H. Chiang, B.J. Hoffer, H. Rosenheim, N.H. Greig, J.P. Miller, Exendin-4 ameliorates traumatic brain injury-induced cognitive impairment in rats, PLoS One, 8 (2013) e82016.
[16] B.E. Masel, D.S. DeWitt, Traumatic brain injury: a disease process, not an event, J Neurotrauma, 27 (2010) 1529-1540.
[17] M. Angoa-Perez, M.J. Kane, D.I. Briggs, N. Herrera-Mundo, D.C. Viano, D.M. Kuhn, Animal models of sports-related head injury: bridging the gap between pre-clinical research and clinical reality, J Neurochem, 129 (2014) 916-931.
[18] G.W. Hergenroeder, J.B. Redell, A.N. Moore, P.K. Dash, Biomarkers in the clinical diagnosis and management of traumatic brain injury, Mol Diagn Ther, 12 (2008) 345-358.
[19] C.E. Dixon, B.G. Lyeth, J.T. Povlishock, R.L. Findling, R.J. Hamm, A. Marmarou, H.F. Young, R.L. Hayes, A fluid percussion model of experimental brain injury in the rat, J Neurosurg, 67 (1987) 110-119.
[20] C.E. Dixon, G.L. Clifton, J.W. Lighthall, A.A. Yaghmai, R.L. Hayes, A controlled cortical impact model of traumatic brain injury in the rat, J Neurosci Methods, 39 (1991) 253-262.
[21] J.W. Lighthall, Controlled cortical impact: a new experimental brain injury model, J Neurotrauma, 5 (1988) 1-15.
[22] A. Marmarou, M.A. Foda, W. van den Brink, J. Campbell, H. Kita, K. Demetriadou, A new model of diffuse brain injury in rats. Part I: Pathophysiology and biomechanics, J Neurosurg, 80 (1994) 291-300.
[23] I. Cernak, J. Savic, Z. Malicevic, G. Zunic, P. Radosevic, I. Ivanovic, L. Davidovic, Involvement of the central nervous system in the general response to pulmonary blast injury, J Trauma, 40 (1996) S100-104.
[24] L.Y. Leung, P.J. VandeVord, A.L. Dal Cengio, C. Bir, K.H. Yang, A.I. King, Blast related neurotrauma: a review of cellular injury, Mol Cell Biomech, 5 (2008) 155-168.
[25] Y. Xiong, A. Mahmood, M. Chopp, Animal models of traumatic brain injury, Nat Rev Neurosci, 14 (2013) 128-142.
[26] P. Sengupta, The Laboratory Rat: Relating Its Age With Human''s, Int J Prev Med, 4 (2013) 624-630.
[27] A.N. Bolton, BS, K.E. Saatman, Regional Neurodegeneration and Gliosis Are Amplified by Mild Traumatic Brain Injury Repeated at 24-Hour Intervals, DOI (2014).
[28] B. Liang, J. Fang, Postnatal Isoflurane Exposure Induces Cognitive Impairment and Abnormal Histone Acetylation of Glutamatergic Systems in the Hippocampus of Adolescent Rats, J Mol Neurosci, DOI 10.1007/s12031-016-0756-1(2016).
[29] V. Baumans, P.F. Brain, H. Brugere, P. Clausing, T. Jeneskog, G. Perretta, Pain and distress in laboratory rodents and lagomorphs, DOI (1994).
[30] S.F. Chen, C.W. Hsu, W.H. Huang, J.Y. Wang, Post-injury baicalein improves histological and functional outcomes and reduces inflammatory cytokines after experimental traumatic brain injury, Br J Pharmacol, 155 (2008) 1279-1296.
[31] J.Y. Wang, Y.N. Huang, C.C. Chiu, D. Tweedie, W. Luo, C.G. Pick, S.Y. Chou, Y. Luo, B.J. Hoffer, N.H. Greig, J.Y. Wang, Pomalidomide mitigates neuronal loss, neuroinflammation, and behavioral impairments induced by traumatic brain injury in rat, J Neuroinflammation, 13 (2016) 168.
[32] T.M. Barth, T.A. Jones, T. Schallert, Functional subdivisions of the rat somatic sensorimotor cortex, Behav Brain Res, 39 (1990) 73-95.
[33] L.Y. Yang, N.H. Greig, Y.N. Huang, T.H. Hsieh, D. Tweedie, Q.S. Yu, B.J. Hoffer, Y. Luo, Y.C. Kao, J.Y. Wang, Post-traumatic administration of the p53 inactivator pifithrin-alpha oxygen analogue reduces hippocampal neuronal loss and improves cognitive deficits after experimental traumatic brain injury, Neurobiol Dis, 96 (2016) 216-226.
[34] C. Dillard, N. Ditchman, K. Nersessova, N. Foster, P. Wehman, M. West, B. Riedlinger, E. Monasterio, B. Shaw, J. Neblett, Post-concussion symptoms in mild traumatic brain injury: findings from a paediatric outpatient clinic, Disabil Rehabil, 39 (2017) 544-550.
[35] J. Bruns, Jr., W.A. Hauser, The epidemiology of traumatic brain injury: a review, Epilepsia, 44 Suppl 10 (2003) 2-10.
[36] A. Olsen, J.F. Brunner, K.A. Indredavik Evensen, T.G. Finnanger, A. Vik, T. Skandsen, N.I. Landro, A.K. Haberg, Altered Cognitive Control Activations after Moderate-to-Severe Traumatic Brain Injury and Their Relationship to Injury Severity and Everyday-Life Function, Cereb Cortex, 25 (2015) 2170-2180.
[37] C. Goddeyne, J. Nichols, C. Wu, T. Anderson, Repetitive mild traumatic brain injury induces ventriculomegaly and cortical thinning in juvenile rats, J Neurophysiol, 113 (2015) 3268-3280.
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