Minocycline markedly protects the neonatal brain against hypoxic-ischemic injury
Minocycline markedly protects the neonatal brain against hypoxic-ischemic injury
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DOI：
10.1002/ana.10242
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发表时间：
2002-07-01
影响因子：
11.2
通讯作者：
Holtzman, DM
中科院分区：
文献类型：
--
作者：
Arvin, KL;Han, BH;Holtzman, DM
围产期缺氧缺血性脑损伤是导致发病和死亡的主要原因。目前，还没有有效的治疗方法来保护人类新生儿大脑免受这种类型的损伤。米诺环素是一种半合成四环素，已被证明在某些成人缺血性损伤/中风和神经退行性疾病模型中具有神经保护作用。然而，米诺环素的神经保护作用尚未评估后，侮辱新生儿的大脑。我们现在报告米诺环素给药之前或之后立即缺氧缺血性损伤基本上阻断新生儿缺氧缺血性脑损伤的啮齿动物模型的组织损伤。米诺环素治疗可防止活化的半胱天冬酶-3（一种已知的细胞凋亡效应物）的形成，以及钙蛋白酶裂解底物（一种兴奋性毒性/坏死性细胞死亡的标志物）的出现。据我们所知，这是第一个报告的系统治疗，可以管理后，缺氧缺血性损伤，这提供了强大的，几乎完全的神经保护发育中的大脑。我们的数据表明，米诺环素或相关的神经保护四环素可能是一个候选人，考虑在人类临床试验中，以保护发育中的大脑免受缺氧缺血性损伤。
Hypoxic-ischemic brain injury in the perinatal period is a major cause of morbidity and mortality. Presently, there are no proven effective therapies with which to safeguard the human neonatal brain against this type of injury. Minocycline, a semisynthetic tetracycline, has been shown to be neuroprotective in certain adult ischemic injury/stroke and neurodegenerative disease models. However, minocycline's neuroprotective effects have not been assessed after insults to the neonatal brain. We now report that minocycline administered either immediately before or immediately after a hypoxic-ischemic insult substantially blocks tissue damage in a rodent model of neonatal hypoxic-ischemic brain injury. Minocycline treatment prevents the formation of activated caspase-3, a known effector of apoptosis, as well as the appearance of a calpain cleaved substrate, a marker of excitotoxic/necrotic cell death. To our knowledge, this is the first report of a systemic treatment that can be administered after a hypoxic-ischemic insult, which provides robust, nearly complete neuroprotection to the developing brain. Our data suggest that minocycline or a related neuroprotective tetracycline may be a candidate to consider in human clinical trials to protect the developing brain against hypoxic-ischemic-induced damage.