摘要或動機

超音波應用於臨床已行之有年，而以穿透式超音波打入腦部的想法也已提出，本實驗目的即為測試低強度間歇性超音波達到腦部受傷後治療的可能。本實驗採用星狀細胞培養模式來探討，首先以腫瘤壞死因子α(Tumor Necrosis Factor-α, TNF-α)模擬中風缺氧的狀態，並利用低強度間歇性超音波刺激星狀細胞，然後檢測其培養液中一氧化氮(nitric oxide, NO)的濃度變化，以及大腦衍生神經營養因子(Brain-derived Neurotrophic Factor, BDNF)、神經膠質衍生神經營養因子(Glial-derived Neurotrophic Factor, GDNF)之mRNA 表現的情形。由實驗結果顯示，在TNF-α存在狀況下則能使NO 濃度上升，施打低強度間歇性超音波可促使NO 增加，並提升上述BDNF、GDNF 兩種蛋白質之mRNA 表現，BDNF 可幫助支持神經元生存，促使新神經元和突觸的發展及分化；GDNF 可有效提昇許多類型神經元生存率；而適當之NO 濃度可以調節神經傳遞物質釋放和腦血流，乃至於影響到記憶的產生。我們初步的結果也顯示在TNF-α存在下，超音波可以增加BDNF 及GDNF 蛋白之產生，因此本研究成果顯示低強度間歇性超音波可提供有利於神經元的環境。The ultrasound technology has been widely applied in the clinical practice for many years, such as monitoring of fetus, lithotripsy, rehabilitation after fracture, as well as the ultrasound stimulation of brain tissue, etc. The purpose of this study is to investigate the therapeutic effect of low intensity pulsed ultrasound (LIPUS) on the injured brain. In this study, we adopted the in vitro model of astrocyte cultures. The tumor necrosis factor- α (TNF-α) was used to simulate the condition of ischemic stroke. We used LIPUS to stimulate the cultured astrocytes, then we ssessed the concentration of nitric oride (NO) in the culture medium. We also assessed the expression of messenger RNA (mRNA) of both brain-derived neurotrophic factor (BDNF) and glial cell-derived neurotrophic factor (GDNF). The results showed that NO increased after the addition of TNF- α. In addition, treatment of LIPUS increased the expression of NO, as well as the mRNA of both BDNF and GDNF. The BDNF is able to support the survival of neuron, as well as stimulate differentiation of neurons and synapses. GDNF can also increase the survival of various kinds of neurons. Furthermore, NO may regulate the secretion of neurotransmitters, increase the blood flow in the brain, as well as enhance the processing of memory. Our preliminary results also demonstrated that both BDNF and GDNF protein increased in response to LIPUS in the presence of TNF-α. Therefore, treatment with LIPUS implicated an environment favoring the protection of neurons.