Division of Bioinformation and Therapeutic Systems, National Defense Medical College Research Institute, Tokorozawa, Saitama, Japan.
Defence Research and Development Canada, Suffield Research Centre, Medicine Hat, Alberta, Canada.
J Neurotrauma. 2024 Aug;41(15-16):e2039-e2053. doi: 10.1089/neu.2023.0572. Epub 2024 May 8.
In the past decade, signature clinical neuropathology of blast-induced traumatic brain injury has been under intense debate, but interface astroglial scarring (IAS) seems to be convincing. In this study, we examined whether IAS could be replicated in the rat brain exposed to a laser-induced shock wave(s) (LISW[s]), a tool that can produce a pure shock wave (primary mechanism) without dynamic pressure (tertiary mechanism). Under certain conditions, we observed astroglial scarring in the subpial glial plate (SGP), gray-white matter junctions (GM-WM), ventricular wall (VW), and regions surrounding cortical blood vessels, accurately reproducing clinical IAS. We also observed shock wave impulse-dependent meningeal damage (dural microhemorrhage) by transcranial near-infrared (NIR) reflectance imaging. Importantly, there were significant correlations between the degree of dural microhemorrhage and the extent of astroglial scarring more than 7 days post-exposure, suggesting an association of meningeal damage with astroglial scarring. The results demonstrated that the primary mechanism alone caused the IAS and meningeal damage, both of which are attributable to acoustic impedance mismatching at multi-layered tissue boundaries. The time course of glial fibrillary acidic protein (GFAP) immunoreactivity depended not only on the LISW conditions but also on the regions. In the SGP, significant increases in GFAP immunoreactivity were observed at 3 days post-exposure, whereas in the GM-WM and VW, GFAP immunoreactivity was not significantly increased before 28 days post-exposure, suggesting different pathological mechanisms. With the high-impulse single exposure or the multiple exposure (low impulse), fibrotic reaction or fibrotic scar formation was observed, in addition to astroglial scarring, in the cortical surface region. Although there are some limitations, this seems to be the first report on the shock-wave-induced IAS rodent model. The model may be useful to explore potential therapeutic approaches for IAS.
在过去的十年中，爆炸引起的创伤性脑损伤的特征性临床神经病理学一直存在激烈的争论，但界面星形胶质瘢痕（IAS）似乎令人信服。在这项研究中，我们研究了激光诱导冲击波（LISW）暴露的大鼠脑中是否可以复制 IAS，这种工具可以产生纯冲击波（主要机制）而没有动压（三级机制）。在某些条件下，我们观察到在软脑膜下胶质层（SGP）、灰质-白质交界处（GM-WM）、脑室壁（VW）和皮质血管周围区域出现星形胶质瘢痕，准确地再现了临床 IAS。我们还通过颅穿透近红外（NIR）反射成像观察到冲击波脉冲依赖性脑膜损伤（硬脑膜微出血）。重要的是，暴露后 7 天以上，脑膜微出血的程度与星形胶质瘢痕的程度之间存在显著相关性，表明脑膜损伤与星形胶质瘢痕有关。结果表明，仅主要机制就会导致 IAS 和脑膜损伤，这两者都是由于多层组织边界的声阻抗不匹配引起的。胶质纤维酸性蛋白（GFAP）免疫反应的时间进程不仅取决于 LISW 条件，还取决于区域。在 SGP 中，暴露后 3 天观察到 GFAP 免疫反应显著增加，而在 GM-WM 和 VW 中，暴露后 28 天前 GFAP 免疫反应没有明显增加，这表明存在不同的病理机制。高脉冲单次暴露或多次（低脉冲）暴露除了星形胶质瘢痕外，在皮质表面区域还观察到纤维反应或纤维瘢痕形成。虽然存在一些限制，但这似乎是第一个关于冲击波诱导的 IAS 啮齿动物模型的报告。该模型可能有助于探索 IAS 的潜在治疗方法。
