Lee Kong Chian School of Medicine, Nanyang Technological University, 59 Nanyang Drive, Singapore 636921, Singapore.
Cognitive Neuroimaging Centre, Nanyang Technological University, 59 Nanyang Drive, Singapore 636921, Singapore.
Int J Mol Sci. 2021 Jan 19;22(2):951. doi: 10.3390/ijms22020951.
Traumatic brain injury (TBI) modelled by lateral fluid percussion-induction (LFPI) in rats is a widely used experimental rodent model to explore and understand the underlying cellular and molecular alterations in the brain caused by TBI in humans. Current improvements in imaging with positron emission tomography (PET) have made it possible to map certain features of TBI-induced cellular and molecular changes equally in humans and animals. The PET imaging technique is an apt supplement to nanotheranostic-based treatment alternatives that are emerging to tackle TBI. The present study aims to investigate whether the two radioligands, [C]PBR28 and [F]flumazenil, are able to accurately quantify in vivo molecular-cellular changes in a rodent TBI-model for two different biochemical targets of the processes. In addition, it serves to observe any palpable variations associated with primary and secondary injury sites, and in the affected versus the contralateral hemispheres. As [C]PBR28 is a radioligand of the 18 kD translocator protein, the up-regulation of which is coupled to the level of neuroinflammation in the brain, and [F]flumazenil is a radioligand for GABA-benzodiazepine receptors, whose level mirrors interneuronal activity and eventually cell death, the use of the two radioligands may reveal two critical features of TBI. An up-regulation in the [C]PBR28 uptake triggered by the LFP in the injured (right) hemisphere was noted on day 14, while the uptake of [F]flumazenil was down-regulated on day 14. When comparing the left (contralateral) and right (LFPI) hemispheres, the differences between the two in neuroinflammation were obvious. Our results demonstrate a potential way to measure the molecular alterations in a rodent-based TBI model using PET imaging with [C]PBR28 and [F]flumazenil. These radioligands are promising options that can be eventually used in exploring the complex in vivo pharmacokinetics and delivery mechanisms of nanoparticles in TBI treatment.
创伤性脑损伤（TBI）通过侧方液体冲击诱导（LFPI）在大鼠中建模，是一种广泛用于探索和理解人类 TBI 引起的大脑中细胞和分子变化的基础的实验性啮齿动物模型。正电子发射断层扫描（PET）成像技术的当前改进使得能够在人类和动物中同样描绘 TBI 诱导的细胞和分子变化的某些特征。PET 成像技术是一种很好的补充，适用于新兴的纳米治疗选择，以解决 TBI 问题。本研究旨在探讨两种放射性配体[C]PBR28 和 [F]氟马西尼是否能够准确地定量活体分子细胞变化在两种不同生化靶点的啮齿动物 TBI 模型中。此外，它还可以观察到与原发性和继发性损伤部位以及受影响对侧半球相关的任何明显变化。由于 [C]PBR28 是 18 kD 转位蛋白的放射性配体，其上调与大脑中的神经炎症水平有关，而 [F]氟马西尼是 GABA-苯二氮䓬受体的放射性配体，其水平反映了中间神经元的活性，最终反映了细胞死亡，因此两种放射性配体的使用可能揭示 TBI 的两个关键特征。在受伤（右侧）半球中，LFP 触发的 [C]PBR28 摄取上调在第 14 天被注意到，而 [F]氟马西尼的摄取在第 14 天被下调。当比较左（对侧）和右（LFPI）半球时，两者之间的神经炎症差异明显。我们的结果表明，使用 [C]PBR28 和 [F]氟马西尼进行 PET 成像，是一种测量基于啮齿动物的 TBI 模型中分子变化的潜在方法。这些放射性配体是很有前途的选择，最终可以用于探索 TBI 治疗中纳米粒子的复杂体内药代动力学和传递机制。
