Institute for Stroke and Dementia Research (ISD) and Ludwig-Maximilians-University (LMU) Munich Medical Center, Munich, Germany.
First Teaching Hospital of the Tianjin University of Traditional Chinese Medicine, Tianjin, China.
J Neurotrauma. 2021 Feb 15;38(4):399-410. doi: 10.1089/neu.2020.7271. Epub 2020 Oct 30.
Vasogenic brain edema (VBE) formation remains an important factor determining the fate of patients with traumatic brain injury (TBI). The spatial and temporal development of VBE, however, remains poorly understood because of the lack of sufficiently sensitive measurement techniques. To close this knowledge gap, we directly visualized the full time course of vascular leakage after TBI by 2-photon microscopy (2-PM). Male C57BL/6 mice ( = 6/group, 6-8 weeks old) were assigned randomly to sham operation or brain trauma by controlled cortical impact. A cranial window was prepared, and tetramethylrhodamine-dextran (TMRM, MW 40,000 Da) was injected intravenously to visualize blood plasma 4 h, 24 h, 48 h, 72 h, or seven days after surgery or trauma. Three regions with increasing distance to the primary contusion were investigated up to a depth of 300 μm by 2-PM. No TMRM extravasation was detected in sham-operated mice, while already 4 h after TBI vascular leakage was significantly increased ( < 0.05 vs. sham) and reached its maximum at 48 h after injury. Vascular leakage was most pronounced in the vicinity of the contusion. The rate of extravasation showed a biphasic pattern, peaking 4 h and 48-72 h after trauma. Taken together, longitudinal quantification of vascular leakage after TBI demonstrates that VBE formation after TBI develops in a biphasic manner suggestive of acute and delayed mechanisms. Further studies using the currently developed dynamic imaging modalities are needed to investigate these mechanisms and potential therapeutic strategies in more detail.
血管源性脑水肿（VBE）的形成仍然是决定创伤性脑损伤（TBI）患者命运的重要因素。然而，由于缺乏足够敏感的测量技术，VBE 的时空发展仍然知之甚少。为了弥补这一知识空白，我们通过双光子显微镜（2-PM）直接可视化 TBI 后血管渗漏的完整时程。雄性 C57BL/6 小鼠（每组 = 6，6-8 周龄）随机分为假手术或脑外伤组。制备颅窗，静脉注射四甲基罗丹明-葡聚糖（TMRM，MW 40,000 Da），以在手术后或创伤后 4 小时、24 小时、48 小时、72 小时或 7 天可视化血浆。通过 2-PM 研究了距原发性挫伤区距离增加的三个区域，深度达 300μm。假手术组未检测到 TMRM 外渗，而 TBI 后 4 小时血管渗漏明显增加（<0.05 与假手术组相比），并在损伤后 48 小时达到最大值。血管渗漏在挫伤区附近最为明显。外渗率呈双峰模式，在创伤后 4 小时和 48-72 小时达到峰值。总之，TBI 后血管渗漏的纵向定量研究表明，TBI 后 VBE 的形成呈双相方式发展，提示存在急性和延迟机制。需要进一步使用当前开发的动态成像方式研究这些机制和潜在的治疗策略。
