Han Qinghua, Brenes David, Bishop Kevin W, Pichon Trey J, Ling Melissa, McPheron Garrett D, White Nathan J, Pun Suzie H, Liu Jonathan T C, Sellers Drew L
Department of Bioengineering, University of Washington, Seattle, WA 98195, USA.
Department of Mechanical Engineering, University of Washington, Seattle, WA 98195, USA.
Sci Adv. 2025 Jul 18;11(29):eadw7425. doi: 10.1126/sciadv.adw7425.
Traumatic brain injury (TBI) often induces blood leakage into brain tissues, which causes further tissue loss after the initial injury. To mitigate this secondary injury, we hypothesized that delivery of a fibrin-binding hemostatic polymer, PolySTAT, would act as a molecular patch and ameliorate brain vessel damage following TBI. We developed a three-dimensional (3D) pathology and analysis workflow to quantify the effects of PolySTAT versus a control polymer, PolySCRM, on neurovascular networks and neural tissue in whole mouse brains. Using a panel of fluorescent probes, our 3D pathology pipeline revealed that PolySTAT treatment preserves neurovascular density and function, reduces hypoxia and blood extravasation, and reduces brain tissue loss after TBI. To further corroborate the 3D microscopy-based findings, gene expression analyses show that PolySTAT attenuates the expression of inflammation and reactive gliosis biomarkers. These findings support future translational investigation of intravenous PolySTAT as an early post-injury therapy to mitigate neural tissue loss after TBI.
创伤性脑损伤（TBI）常导致血液渗漏至脑组织中，这在初始损伤后会导致进一步的组织损失。为减轻这种继发性损伤，我们推测，递送一种纤维蛋白结合止血聚合物PolySTAT，将起到分子补片的作用，并改善TBI后的脑血管损伤。我们开发了一种三维（3D）病理学及分析流程，以量化PolySTAT与对照聚合物PolySCRM对整个小鼠大脑神经血管网络和神经组织的影响。使用一组荧光探针，我们的3D病理学流程显示，PolySTAT治疗可保留神经血管密度和功能，减少缺氧和血液外渗，并减少TBI后的脑组织损失。为进一步证实基于3D显微镜的研究结果，基因表达分析表明，PolySTAT可减弱炎症和反应性胶质增生生物标志物的表达。这些发现支持未来将静脉注射PolySTAT作为损伤后早期治疗方法，以减轻TBI后神经组织损失的转化研究。
