缺血性腦中風導致腦部傷害且破壞腦神經血管構造因而造成腦部水腫產生。
過去研究發現褪黑激素是一種強而有效之自然抗氧化劑與自由基截取劑。近年來有許多研究指出褪黑激素於急性缺血性腦中風有強而有效的神經保護作用。在本研究中，利用ICR小白鼠進行持續性中大腦動脈電燒結紮手術模擬中風，並以褪黑激素治療，評估其神經保護特性與其血腦屏障功能。實驗中，老鼠在模擬完中風後給予5 mg/kg的褪黑激素治療。老鼠存活24小時之後，應用影像軟體處理系統計算Nissl染色腦切片之栓塞大小並評估栓塞後個別神經運動感覺功能，腦血流以及使用1% 伊凡斯藍(Evans blue)的染劑注入老鼠體內來觀察血腦屏障功能。除此之外，利用西方點漬法觀察基質金屬蛋白酶第九型(MMP-9)、水通道蛋白第四型(Aquaporin-4)以及緊密聯合(Tight -junction)蛋白的表現量。實驗結果表示，在中大腦動脈栓塞24小時老鼠給予每公斤五毫克的褪黑激素治療後與PEG-saline實驗控制組比較，腦梗塞和水腫的體積有些微下降。而藉由伊凡斯藍的染劑之結果觀察，發現到褪黑激素治療組老鼠的血腦屏障的完整性比PEG-saline控制組來的好，顯示出褪黑激素加強了血腦屏障的功能。在蛋白質的表現中也看到了在褪黑激素治療後，基質金屬蛋白酶第九型的表達量有下降趨勢;而和緊密聯合有關的蛋白在受傷後的確比正常情況低，但給予治療的老鼠表達量較高的完整性。相反地，水通道蛋白第四型有較低的表達量，顯示出褪黑激素似乎有細胞型水腫發生的情形。本研究證實褪黑激素是對於腦部損傷後有著保護作用，其機制為保護血腦屏障之完整性藉而達到降低血管型腦水腫發生的情形。

Cerebral ischemia stroke can cause damage to the neurovascular unit and formation of brain edema. Melatonin (N-aceyl-5-methoxytryptamine) is a well-known, potent free radical scavenger and an antioxidant. Therefore, a series of experiments with delayed treatment of melatonin have been employed to examine whether exogenous melatonin offers neuroprotective action against middle cerebral artery occlusion (MCAo). In this study, adult male ICR mice were subjected to MCA ligation. Melatonin (5 mg/kg) or vehicle were given before MCA ligation. Brains were sectioned and stained using Nissl stain. Then, software was used to calculate infarction size, brain edema and cell count. 1% Evans Blue was injected after MCA ligation to observe the integrity of blood- brain barrier (BBB). We used neurobehavioral outcome measures to evaluate the ability of motor and sense. The protein expression of aquaporin-4 (AQP-4), Matrix metalloproteinases-9 (MMP-9) and Tight junction protein were determined by Western blotting at 24 hours of ligation. Treatment with melatonin reduced the infarction size and brain swelling after middle cerebral artery ligation. Our results indicate that the administration of melatonin reduced the size of cortical and infarction and brain edema after ischemia. Treatment with melatonin can protect the compromised structure of BBB after MCAO. The decrease of expression of aquaporin-4 may be associated with brain edema after treatment with melatonin. Our studies suggest that melatonin-treated animals not only have reduced brain damage but also decreased brain vasogenic edema after ischemia.

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