最近研究證實攫取自由基有益於治療人類缺血性腦中風（New EnglJ Med 2006 ; 354 : 588 一600 ）。缺血性腦中風之術後出血（hemorrhagic transformation ）為一種嚴重神經 併發症。發展安全有效神經保護治劑，來降低術後出血，對於腦中風治療相當重要。我 們實驗室已建立局部缺血性腦中風後出血之實驗模式，我們想以此模式評估褪黑激素降 低腦中風復出血的程度。 先前我們已証實褪黑激素能保護腦中風後灰質與白質，亦能改善腦神經電氣功 能與神經功能（Lee EJ et al : J Pineal Res 2004 ; 36 ( 1 ) : 33 一42 and J Pineal Res . 2005 ; 38 ( 1 ) : 42 一52 ）。最近我們實驗室又証實褪黑激素能有效降低中風後血腦障礙的氣化與硝 化傷害，並能保有其穿透性（Lee EJ et al : J Pineal Res 2006 ; 41 : 1 75 一1 82 ）。 在本計劃中，我們將釐清褪黑激素於實驗動物腦中風作用機轉；包含降低中風後 MMPs 之向上調節、腦水腫及腦中風後出血與神經保護作用等。另外，我們將探討褪黑 激素在本實驗模式下，降低傷害的可能機轉。這些實驗結果，期盼使用褪黑激素治療臨床上缺血性腦中風出血的病息有所幫助。
Free radical scavenger has recently proven to be beneficial for ischemic stroke in human beings (New Engl J Med 2006; 354:588-600). Unpredictable hemorrhagic transformation, however, comes with reperfusion and represents a severe neurological complication after cerebral ischemia-reperfusion. Neuroprotection aimed at decreasing the extent of hemorrhagic transformation is, therefore, crucial in the context of stroke therapy. We have already developed a model of focal cerebral ischemia in our Lab with delayed hemorrhagic transformation. The beneficial effects of melatonin with regards to decreasing hemorrhagic transformation therapy will be evaluated in the model. We have previously shown that melatonin protects against ischemic grey and white matter damage and improves electrophysiological and functional outcome in models of cerebral ischemia-reperfusion in mice and rats, respectively (Lee et al: J Pineal Res 2004; 36(1):33-42 and J Pineal Res. 2005;38(1):42-52). More recently, we have also shown that melatonin has the ability to decrease post-ischemic oxidative/nitrosative damage to the ischemic neurovascular units and improved the preservation of BBB permeability at an early phase following transient focal ischemia in our Lab. (J Pineal Res 2006; In the grant, we will further clarify the possible mechanisms of action of melatonin, involving a decrease in post-ischemic up-regulation of metalloproteinase and, thus, brain edema and hemorrhagic transformation, which may further justify neuroprotective actions observed with melatonin in experimental stroke model. In addition, we will pursue the putative mechanisms of action by which melatonin reduce the damage due to reperfusion-induced hemorrhagic transformation in the model. These results may be of help for clinical application of melatonin in the field of reperfusion-relevant hemorrhagic transformation stroke patients.
