Department of Neurosurgery, Shanghai Jiao Tong University School of Medicine, Shanghai, China.
J Neurotrauma. 2011 Dec;28(12):2513-21. doi: 10.1089/neu.2011.1958. Epub 2011 Nov 2.
Previous studies revealed that curcumin is neuroprotective in diseases of the central nervous system such as cerebral ischemia and traumatic brain injury. However, the effect of curcumin on intracerebral hemorrhage remains unclear. We, therefore, investigated the pre-clinical effect of curcumin treatment on neurological outcomes following intracerebral hemorrhage, using a mouse model. Intracerebral hemorrhage was induced by autologous blood injection into the right basal ganglia. Curcumin (150 mg/kg) was administered 15 min after intracerebral hemorrhage. Grid walk and neurological scores were evaluated at 1, 3, 7, and 14 days post-injury. Mice were killed at 24 h or 28 days following injury, for histological examination. Evans Blue and water content in the ipsilateral and contralateral hemispheres were measured to evaluate the extent of blood-brain barrier disruption and brain edema. Zonula occludens-1 was detected by immunostaining. In situ zymography was used to measure the localization and focal enzymatic activity of matrix metalloproteinase. Our results demonstrated that curcumin reduced brain edema, measured by alleviated water content and Evans Blue leakage at 24 h (p<0.05). Lateral ventricle measurements indicated that curcumin reduced brain tissue loss in the ipsilateral hemisphere (p<0.05). The same dose of curcumin also significantly attenuated neurological deficits at 1 and 3 days of intracerebral hemorrhage (p<0.05). Immunostaining showed that tight junction continuity around the hematoma was better sustained in curcumin-treated mice than in vehicle-treated mice. At 24 h, the number of matrix metalloproteinase-positive cells was significantly reduced by curcumin (p<0.05). Our study suggests that curcumin ameliorates intracerebral hemorrhage damage by preventing matrix metalloproteinase-mediated blood-brain barrier damage and brain edema, which might provide therapeutic potential for intracerebral hemorrhage.
先前的研究表明姜黄素在脑缺血和创伤性脑损伤等中枢神经系统疾病中具有神经保护作用。然而，姜黄素对脑出血的影响尚不清楚。因此，我们使用小鼠模型研究了姜黄素治疗对脑出血后神经功能的临床前影响。通过向右侧基底核注射自体血液来诱导脑出血。脑出血后 15 分钟给予姜黄素（150mg/kg）。在损伤后 1、3、7 和 14 天评估网格行走和神经评分。在损伤后 24 小时或 28 天处死小鼠，进行组织学检查。通过免疫染色检测闭合蛋白-1。通过 Evans Blue 和同侧和对侧半球的水含量来评估血脑屏障破坏和脑水肿的程度。通过原位酶谱测定来测量基质金属蛋白酶的定位和局部酶活性。我们的结果表明，姜黄素通过减轻 24 小时时的水含量和 Evans Blue 渗漏来减轻脑水肿（p<0.05）。侧脑室测量表明，姜黄素减轻了同侧半球的脑组织损失（p<0.05）。相同剂量的姜黄素也显著减轻了脑出血后 1 天和 3 天的神经功能缺损（p<0.05）。免疫染色显示，姜黄素处理的小鼠血肿周围的紧密连接连续性比载体处理的小鼠更好。在 24 小时时，姜黄素显著减少了基质金属蛋白酶阳性细胞的数量（p<0.05）。我们的研究表明，姜黄素通过防止基质金属蛋白酶介导的血脑屏障损伤和脑水肿来改善脑出血损伤，这可能为脑出血提供治疗潜力。
