A Multi-Model Pipeline for Translational Intracerebral Haemorrhage Research.
A Multi-Model Pipeline for Translational Intracerebral Haemorrhage Research.
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DOI：
10.1007/s12975-020-00830-z
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发表时间：
2020-12
影响因子：
6.9
通讯作者：
Kasher PR
中科院分区：
文献类型：
--
作者：
Withers SE;Parry-Jones AR;Allan SM;Kasher PR
除了急性和慢性血压降低，我们没有特定的药物来预防脑出血（ICH）或改善出血后的结局。其中一个原因可能与当前ICH临床前模型相关的特定限制有关，导致未能转化为临床。目前，转化型ICH研究的“药物开发管道”似乎出现了故障，需要紧急解决。在这里，我们回顾了最常用的ICH临床前模型，并讨论了它们在转化研究中的优点和缺点。我们建议，为了增加我们成功识别ICH新疗法的机会，使用一种以上模型物种/系统的双向、2管或3管方法可能有助于确认关键的临床前观察结果。此外，我们强调，死后/离体ICH患者材料是一种珍贵且未充分利用的资源，在考虑进行进一步临床研究之前，可以在实验结果的验证中发挥重要作用。临床前和临床ICH研究小组之间的多学科合作对于确保这种方法在未来取得成功至关重要。
Apart from acute and chronic blood pressure lowering, we have no specific medications to prevent intracerebral haemorrhage (ICH) or improve outcomes once bleeding has occurred. One reason for this may be related to particular limitations associated with the current pre-clinical models of ICH, leading to a failure to translate into the clinic. It would seem that a breakdown in the ‘drug development pipeline’ currently exists for translational ICH research which needs to be urgently addressed. Here, we review the most commonly used pre-clinical models of ICH and discuss their advantages and disadvantages in the context of translational studies. We propose that to increase our chances of successfully identifying new therapeutics for ICH, a bi-directional, 2- or 3-pronged approach using more than one model species/system could be useful for confirming key pre-clinical observations. Furthermore, we highlight that post-mortem/ex-vivo ICH patient material is a precious and underused resource which could play an essential role in the verification of experimental results prior to consideration for further clinical investigation. Embracing multidisciplinary collaboration between pre-clinical and clinical ICH research groups will be essential to ensure the success of this type of approach in the future.
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