Neurophysiology Laboratory, Neurosurgical Service, Department of Surgery, National Cheng Kung University Medical Center and Medical School, Tainan, Taiwan.
Crit Care Med. 2011 May;39(5):1130-7. doi: 10.1097/CCM.0b013e31820a9442.
We have previously shown that cinnamophilin ([8R, 8'S]-4, 4'-dihydroxy-3, 3'-dimethoxy-7-oxo-8, 8'-neolignan) exhibited potent antioxidant, radical-scavenging, and anti-inflammatory actions and reduced acute ischemic brain damage, even when it was given up to 6 hrs postinsult. Here, we characterized the long-lasting neuroprotection of cinnamophilin against gray and white matter damage and its beneficial effects on electrophysiological and functional outcomes in a model of stroke.
Prospective laboratory animal study.
Research laboratory in a university teaching hospital.
Adult male Sprague-Dawley rats (240-290 g).
Under controlled conditions of normoxia, normocarbia, and normothermia, spontaneously breathing, halothane-anesthetized (1.0-1.5%) rats were subjected to transient middle cerebral artery occlusion for 90 mins. Cinnamophilin (80 mg/kg) or vehicle was given intravenously at reperfusion onset.
Physiological parameters, including arterial blood gases and cortical blood perfusion, somatosensory-evoked potentials, and neurobehavioral outcomes, were serially examined. Animals were euthanized at 7 days or 21 days postinsult. Gray matter and white matter (axonal and myelin) damage were then evaluated by quantitative histopathology and immunohistochemistry against phosphorylated component-H neurofilaments and myelin basic protein, respectively. After the follow-up period of 7 and 21 days, our results showed that cinnamophilin significantly decreased gray matter damage by 31.6% and 34.9% (p < .05, respectively) without notable adverse effects. Additionally, cinnamophilin effectively reduced axonal and myelin damage by 46.3-68.6% (p < .05) and 25.2-28.1% (p < .05), respectively. Furthermore, cinnamophilin not only improved the ipsilateral field potentials (p < .05, respectively), but also reduced the severity of contralateral electrophysiological diaschisis (p < .05). Consequently, cinnamophilin improved sensorimotor outcomes up to 21 days postinsult (p < .05, respectively).
Administration with cinnamophilin provides long-lasting neuroprotection against gray and white matter damage and improves functional and electrophysiological outcomes after ischemic stroke. The results suggest a need for further studies to characterize the potential of cinnamophilin in the field of ischemic stroke.
我们之前已经证明，肉桂醇（[8R，8'S]-4,4'-二羟基-3,3'-二甲氧基-7-氧代-8,8'-新木脂素）具有强大的抗氧化、自由基清除和抗炎作用，并能减轻急性缺血性脑损伤，甚至在损伤后 6 小时给予该物质仍有效果。在这里，我们研究了肉桂醇对灰白质损伤的长期神经保护作用及其对中风模型中电生理和功能结果的有益影响。
前瞻性实验室动物研究。
大学教学医院的研究实验室。
成年雄性 Sprague-Dawley 大鼠（240-290g）。
在正常氧、正常碳酸和正常体温条件下，使用异氟烷（1.0-1.5%）麻醉的、自主呼吸的大鼠，进行 90 分钟的短暂性大脑中动脉闭塞。肉桂醇（80mg/kg）或载体在再灌注开始时静脉给予。
连续检查生理参数，包括动脉血气和皮质血流、体感诱发电位和神经行为结果。动物在损伤后 7 天或 21 天被安乐死。然后通过定量组织病理学和针对磷酸化元件-H 神经丝和髓鞘碱性蛋白的免疫组织化学，分别评估灰白质和白质（轴突和髓鞘）损伤。在 7 天和 21 天的随访期后，我们的结果表明，肉桂醇可使灰白质损伤分别减少 31.6%和 34.9%（p<.05），且无明显不良反应。此外，肉桂醇还可有效减少 46.3-68.6%（p<.05）和 25.2-28.1%（p<.05）的轴突和髓鞘损伤。此外，肉桂醇不仅改善了同侧场电位（p<.05），还减轻了对侧电生理失神经支配的严重程度（p<.05）。因此，肉桂醇可改善损伤后 21 天的感觉运动结果（p<.05）。
肉桂醇的给药可提供长期的灰白质损伤神经保护作用，并改善缺血性中风后的功能和电生理结果。这些结果表明需要进一步研究来确定肉桂醇在缺血性中风领域的潜力。
