頭部創傷研究動物模式之建立及神經滋養因子治療之療效

回顧Jennett and Frankowski在1990年所發布之統計顯示嚴重之頭部外傷每年約有10,000,000人次(200-300/100,000)，他們可能喪失工作能力或需要社會之巨大醫藥資源之付出。台灣在每年之前十大死亡原因當中，意外傷害在近數年來一直是站在第四位，其中交通事故傷害佔有一半之機率，而交通事故之一半事頭部外傷。臨床上常可看見嚴重頭部創傷的病患因腦浮腫及其續發病變而死亡，過去的許多研究與臨床發現也證實頭部創傷後可因腦血管擴張充血、腦血流量的改變及自我調節功能的喪失造成續發性的病變。然而創傷後連續性的腦血流及血管病變的偵測研究並不多，更不明瞭何種機轉造成血管擴張充血及腦血流增加。有關頭部創傷後的腦血流及動力學研究在人身上的報告較少，更缺乏受創後最初藥物治療的資料。本計畫的第一個目的即是利用本部已成熟之腦缺血研究技術及缺血性大白鼠動物模式之建立，加上最近創傷模式穩定實驗結果。了解頭部創傷後腦血管之變化。經由對照創傷三組的相互比較結果，將可得知頭部創傷後的腦血管變化在藥物治療之效用。最近在新的研就報告顯示移植人類胚胎幹細胞株可以改善中風動物的運動功能，且移植細胞的數目與運動功能的改善成正比；本國的研究發現，神經幹細胞是一個很好移植用的細胞來源，他們可以保護神經細胞及改善神經功能障礙，在腦中風傷害有修補之作用。本研究計畫是在驗證是否羊水神經幹細胞及基因治療對頭部外傷造成之腦損傷亦有修補之作用：利用TTC及免疫化學染色方法分析實驗動物腦部的受傷體積及比較實驗動物在給予神經幹細胞與基因治療後對腦受傷恢復之影響。

關鍵字

頭部外傷；神經幹細胞；神經保護作用

並列摘要

From the Head and Spinal cord injury research held in the First International symposium of the Epidemiology of head and Spinal Cord Injury, an incidence of severe head injuries is 200-300/100,000 per year for the total world population of 5.4 billion(Jennett and frankowski,1990). This is an enormous global burden with regard to both loss of manpower and cost. We went to test the potential pathophysiological roles of traumatic ischemia in brain infusion. Acute brain ischemic is usually caused by thromboembolic occlusion of a cerebral artery [58]. Thrombolytic treatment for ischemic is directed to recanalize the occluded cerebral artery to reperfuse the ischemic brain areas. Intravenous or intra-arterial administration of tissue plasminogen activator (tPA) for treatment of acute ischemic stroke has recently been reported.. It suggests that cerebral microvascular permeability might be increased after high-dose tPA treatment. We found that intravenous infusion of 5 and 7.5 mg/kg tPA significantly reduced the cerebral infarction caused by ischemia/reperfusion but 10 mg/kg aggravated it. Increasing evidence suggests that oxidative stress can increase the occurrence of edema, cytokine expression, MMP activation, and apoptosis. It is well known that a loss of vascular integrity results from the degradation of the basal lamina and extracellular matrix.these findings demonstrate the detrimental effect of PUFA such as AA and DHA in post-ischemic progression and brain injury after cerebral I/R is associated with augmentation of cerebral I/R-induced alterations, including oxidative changes. Lastly,stem cell and gene therapy treated group. Rate will be subjected to a lateral fluid percussive brain injury（~5 atm）. TTC will be examined at the light microscopic levels. The results of this proposed experiment should be able to clarify the roles of ischemia in traumatic brain swelling and the effect of stem cell with genes therapy infusion in preventing the secondary vasogenic edema. The preliminary result showed the restoration of brain of neurostem cell and some degree of function recovery,We used immunochemical stain to evaluate the change of volume of trauma and effect of neurostem cell and gene therapy

並列關鍵字

Head Injury ； Neural stem cells ； Neuroprotections

參考文獻

1. Murat E, Gurer G, Gursoy-Ozdemir Y, Karatas H, Dalkara T: A new model of transient focal cerebral ischemia for inducing selevtive neuronal necrosis. Brain Res Bull. 2008 Dec 5.(in press)

2. Amantea D, Nappi G, Bernardi G, Bagetta G, Corasaniti MT:Post-ischemic brain damage:pathophysiology and role of inflammatory mediators. FEBS 276(1):13-26,2009

3. Schilling M, Besselmann M, Leonhard C, Mueller M, Ringelstein EB & Kiefer R (2003) Microglial activation precedes and predominates over macrophage infiltration in transient focal cerebral ischemia: a study in green fluorescent protein transgenic bone marrow chimeric mice. Exp Neurol 183, 25–33. Links

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5. Lindsberg PJ, Carpén O, Paetau A, Karjalainen-Lindsberg ML & Kaste M (1996) Endothelial ICAM-1 expression associated with inflammatory cell response in human ischemic stroke. Circulation 94, 939–945.

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頭部創傷研究動物模式之建立及神經滋養因子治療之療效

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