NIBA-TBI: Neuro-Imaging and biofluid-based Biomarker Assessments as translational pathophysiological outcome measures in TBI

目前，颅脑损伤的临床前研究和动物模型的实验性治疗试验 模型中，最常用的结果终点是病变体积/大小、神经细胞保存 和行为功能结果测量(如Morris水迷宫、旋转木马)。而这些 措施显然是有用的--它们缺乏告知潜在差异的能力 与人脑外伤相关的病理生理机制。这些因素可能导致了 从动物模型疗效到临床缺乏新的脑损伤疗法的翻译成功 试验效果。与神经创伤的翻译结果项目的愿景一致 (TOP-NT)(UG3/UH3)RFA，在这里，我们精心组建了一个多学科团队，并提出 评价两种相辅相成的基于病理机制的脑外伤预后指标--(I)生物体液 生物标记物评估，以及(Ii)MRI-神经成像生物标记物评估。这些评估是选择的 因为它们都是高度定量的，可以很容易地过渡到临床脑损伤研究和 未来的治疗试验。我们的中心假设如下：在临床前多部位 多创伤性脑损伤动物模型的建立、基于生物流体的生物标志物和基于MRI的定量神经成像 生物标记物评估可以发展成有用的转换结果衡量标准，这有助于 介绍一系列临床脑损伤的病理机制亚型，包括轴突损伤， 挫伤/组织坏死、突触连续性丧失、白质损伤、微血管 损伤/脑出血和神经炎症。我们还编制了一份《临床脑损伤》 翻译咨询“小组，协助我们将我们的研究成果转化为临床研究。

Currently, preclinical TBI research and testing of experimental therapeutic in animal models of TBI models, the most commonly used outcome endpoints are lesion volume/size, neuronal cell preservation and behavioral functional outcome measures (such as Morris water maze, rotarod). While these measures are clearly useful – they lack the ability to inform on the underlying distinct pathophysiological mechanisms relevant in human TBI. These factors might have contributed to the lack of translational success for new TBI therapeutics from animal models efficacy to clinical trial efficacy. Consistent with the vision of the Translational Outcomes Project in Neurotrauma (TOP- NT) (UG3/UH3) RFA, here we carefully assembled a multidisciplinary team and proposed to evaluate two complementary pathological mechanism-based TBI outcome measures – (i) biofluid biomarker assessment, and (ii) MRI-neuroimaging biomarker assessment. These assessments are chosen because they are both highly quantitative and can readily transition into clinical TBI studies and future therapeutic trials. Our central hypothesis is as follows: In preclinical multi-site multi-TBI animal model setting, biofluid-based biomarker and quantitative MRI-based neuroimaging biomarker assessment can be developed into useful translational outcome measures that can help address a range of clinical TBI pathological mechanistic subphenotypes including axonal injury, contusion/tissue necrosis, loss of synaptic continuity, white matter injury, microvascular injury/brain hemorrhage and neuroinflammation. We have also put together a “Clinical TBI Translational Advisory” panel to assist us with translating our findings into clinical studies.