Therapeutic targets and limits of minocycline neuroprotection in experimental ischemic stroke.
Therapeutic targets and limits of minocycline neuroprotection in experimental ischemic stroke.
复制标题
DOI：
10.1186/1471-2202-10-126
复制
发表时间：
2009-10-06
期刊：
影响因子：
2.4
通讯作者：
Borlongan CV
中科院分区：
文献类型：
--
作者：
Matsukawa N;Yasuhara T;Hara K;Xu L;Maki M;Yu G;Kaneko Y;Ojika K;Hess DC;Borlongan CV
米诺环素是具有抗炎和抗凋亡特性的第二代四环素，已被证明可促进实验性卒中的治疗益处。然而，同样令人信服的证据表明，该药物在许多神经系统疾病模型中产生可变甚至有害的影响。米诺环素神经保护机制的评估应该阐明该药在急性卒中中的临床价值。在这里，我们表明，米诺环素衰减在体外（氧葡萄糖剥夺）和在体内（大脑中动脉闭塞）实验诱导的缺血性赤字，通过直接抑制神经元细胞死亡，涉及抗凋亡Bcl-2/细胞色素c途径。米诺环素的这种抗凋亡作用在神经元中可见，但在星形胶质细胞中不明显。我们的数据进一步表明，神经保护是剂量依赖性的，因为只有低剂量的米诺环素抑制神经元细胞死亡级联在急性中风阶段，而高剂量加重缺血性损伤。本研究建议我们的社区谨慎使用微创静脉注射低剂量米诺环素，以提供安全的脑卒中神经保护。
Minocycline, a second-generation tetracycline with anti-inflammatory and anti-apoptotic properties, has been shown to promote therapeutic benefits in experimental stroke. However, equally compelling evidence demonstrates that the drug exerts variable and even detrimental effects in many neurological disease models. Assessment of the mechanism underlying minocycline neuroprotection should clarify the drug's clinical value in acute stroke setting. Here, we demonstrate that minocycline attenuates both in vitro (oxygen glucose deprivation) and in vivo (middle cerebral artery occlusion) experimentally induced ischemic deficits by direct inhibition of apoptotic-like neuronal cell death involving the anti-apoptotic Bcl-2/cytochrome c pathway. Such anti-apoptotic effect of minocycline is seen in neurons, but not apparent in astrocytes. Our data further indicate that the neuroprotection is dose-dependent, in that only low dose minocycline inhibits neuronal cell death cascades at the acute stroke phase, whereas the high dose exacerbates the ischemic injury. The present study advises our community to proceed with caution to use the minimally invasive intravenous delivery of low dose minocycline in order to afford neuroprotection that is safe for stroke.
登录
查看更多内容
影响因子：
82.9
作者：
Chen, M;Ona, VO;Friedlander, RM
通讯作者：
Friedlander, RM
影响因子：
3.3
作者：
Flynn, G;Maru, S;Male, D
通讯作者：
Male, D
影响因子：
8.3
作者：
BEDERSON, JB;PITTS, LH;BARTKOWSKI, H
通讯作者：
BARTKOWSKI, H
影响因子：
3.4
作者：
Hunter, CL;Quintero, EM;Granholm, AC
通讯作者：
Granholm, AC
影响因子：
4.2
作者：
Klegeris, A;McGeer, PL
通讯作者：
McGeer, PL