Ramanantsoa Nelina, Fleiss Bobbi, Bouslama Myriam, Matrot Boris, Schwendimann Leslie, Cohen-Salmon Charles, Gressens Pierre, Gallego Jorge
Inserm U676, Hopital Robert Debre, 48 Blvd Serurier, 75019, Paris, France.
Transl Stroke Res. 2013 Apr;4(2):258-77. doi: 10.1007/s12975-012-0233-2. Epub 2012 Dec 21.
The consequences of perinatal brain injury include immeasurable anguish for families and substantial ongoing costs for care and support of effected children. Factors associated with perinatal brain injury in the preterm infant include inflammation and infection, and with increasing gestational age, a higher proportion is related to hypoxic-ischemic events, such as stroke and placental abruption. Over the past decade, we have acquired new insights in the mechanisms underpinning injury and many new tools to monitor outcome in perinatal brain injury in our experimental models. By embracing these new technologies, we can expedite the screening of novel therapies. This is critical as despite enormous efforts of the research community, hypothermia is the only viable neurotherapeutic, and this procedure is limited to term birth and postcardiac arrest hypoxic-ischemic events. Importantly, experimental and preliminary data in humans also indicate a considerable therapeutic potential for melatonin against perinatal brain injury. However, even if this suggested potential is proven, the complexity of the human condition means we are likely to need additional neuroprotective and regenerative strategies. Thus, within this review, we will outline what we consider the key stages of preclinical testing and development for a neuroprotectant or regenerative neurotherapy for perinatal brain injury. We will also highlight examples of novel small animal physiological and behavioral testing that gives small animal preclinical models greater clinical relevance. We hope these new tools and an integrated bench to cribside strategic plan will facilitate the fulfillment of our overarching goal, improving the long-term brain health and quality of life for infants suffering perinatal brain injury.
围产期脑损伤的后果包括给家庭带来难以估量的痛苦，以及为照顾和支持受影响儿童产生持续的巨额费用。与早产儿围产期脑损伤相关的因素包括炎症和感染，随着胎龄增加，更高比例的损伤与缺氧缺血事件有关，如中风和胎盘早剥。在过去十年中，我们对损伤背后的机制有了新的认识，并且在实验模型中有了许多监测围产期脑损伤结果的新工具。通过采用这些新技术，我们可以加快新型疗法的筛选。这至关重要，因为尽管研究界付出了巨大努力，但低温疗法是唯一可行的神经治疗方法，而且该方法仅限于足月儿出生和心脏骤停后缺氧缺血事件。重要的是，人体实验和初步数据也表明褪黑素对围产期脑损伤具有相当大的治疗潜力。然而，即使这一潜在疗效得到证实，人类病情的复杂性意味着我们可能还需要其他神经保护和再生策略。因此，在本综述中，我们将概述我们认为针对围产期脑损伤的神经保护剂或再生神经疗法进行临床前测试和开发的关键阶段。我们还将重点介绍新颖的小动物生理和行为测试示例，这些测试使小动物临床前模型具有更大的临床相关性。我们希望这些新工具和一个从实验室到床边的综合战略计划将有助于实现我们的总体目标，即改善患有围产期脑损伤婴儿的长期脑健康和生活质量。
