实验性血栓栓塞性中风后米诺环素的性别无关神经保护作用
Sex-independent neuroprotection with minocycline after experimental thromboembolic stroke.
作者信息
Hoda Md Nasrul, Li Weiguo, Ahmad Ajmal, Ogbi Safia, Zemskova Marina A, Johnson Maribeth H, Ergul Adviye, Hill William D, Hess David C, Sazonova Irina Y
机构信息
Department of Neurology, Georgia Health Sciences University, Augusta, GA, USA.
出版信息
Exp Transl Stroke Med. 2011 Dec 16;3(1):16. doi: 10.1186/2040-7378-3-16.
BACKGROUND
Minocycline provides neurovascular protection reducing acute cerebral injury. However, it is unclear whether minocycline is effective in females. We tested minocycline in both sexes and aged animals using a novel embolic stroke model in mice that closely mimics acute thromboembolic stroke in humans.
METHODS
Five groups of mice were subjected to thromboembolic stroke: adult males, aged males, adult females, aged females, and adult ovariectomized females. They were treated with phosphate saline (vehicle) or minocycline (6 mg/kg) immediately after stroke onset. Behavioral outcomes, infarct volumes and cerebral blood flow were assessed. The effect of minocycline on expression and activity of MMP-9 was analyzed.
RESULTS
The model resulted in reproducible infarct in the experimental groups. As expected, adult females were significantly more resistant to cerebral ischemic injury than males. This advantage was abolished by aging and ovariectomy. Minocycline significantly reduced the infarct volume (P < 0.0001) and also improved neurologic score (P < 0.0001) in all groups. Moreover, minocycline treatment significantly reduced mortality at 24 hours post stroke (P = 0.037) for aged mice (25% versus 54%). Stroke up-regulated MMP-9 level in the brain, and acute minocycline treatment reduced its expression in both genders (P < 0.0001).
CONCLUSION
In a thromboembolic stroke model minocycline is neuroprotective irrespective of mouse sex and age.
背景
米诺环素具有神经血管保护作用，可减轻急性脑损伤。然而，米诺环素对雌性动物是否有效尚不清楚。我们在雄性和雌性以及老年小鼠中使用一种新型的栓塞性中风模型（该模型紧密模拟人类急性血栓栓塞性中风）对米诺环素进行了测试。
方法
将五组小鼠进行血栓栓塞性中风造模：成年雄性、老年雄性、成年雌性、老年雌性以及成年去卵巢雌性。中风发作后立即用磷酸盐缓冲液（载体）或米诺环素（6毫克/千克）对它们进行治疗。评估行为学结果、梗死体积和脑血流量。分析米诺环素对基质金属蛋白酶-9（MMP-9）表达和活性的影响。
结果
该模型在实验组中导致了可重复的梗死。正如预期的那样，成年雌性对脑缺血损伤的抵抗力明显强于雄性。衰老和去卵巢消除了这一优势。米诺环素显著减小了所有组的梗死体积（P<0.0001），并改善了神经学评分（P<0.0001）。此外，米诺环素治疗显著降低了老年小鼠中风后24小时的死亡率（P = 0.037）（25%对54%）。中风使大脑中MMP-9水平上调，急性米诺环素治疗降低了其在两性中的表达（P<0.0001）。
结论
在血栓栓塞性中风模型中，无论小鼠的性别和年龄如何，米诺环素都具有神经保护作用。
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