Bragin Denis E, Kameneva Marina V, Bragina Olga A, Thomson Susan, Statom Gloria L, Lara Devon A, Yang Yirong, Nemoto Edwin M
1 Department of Neurosurgery, School of Medicine, University of New Mexico, Albuquerque, NM, USA.
2 McGowan Institute for Regenerative Medicine, University of Pittsburgh, Pittsburgh, PA, USA.
J Cereb Blood Flow Metab. 2017 Mar;37(3):762-775. doi: 10.1177/0271678X16684153. Epub 2016 Dec 22.
Cerebral ischemia has been clearly demonstrated after traumatic brain injury (TBI); however, neuroprotective therapies have not focused on improvement of the cerebral microcirculation. Blood soluble drag-reducing polymers (DRP), prepared from high molecular weight polyethylene oxide, target impaired microvascular perfusion by altering the rheological properties of blood and, until our recent reports, has not been applied to the brain. We hypothesized that DRP improve cerebral microcirculation and oxygenation after TBI. DRP were studied in healthy and traumatized rat brains and compared to saline controls. Using in-vivo two-photon laser scanning microscopy over the parietal cortex, we showed that after TBI, nanomolar concentrations of intravascular DRP significantly enhanced microvascular perfusion and tissue oxygenation in peri-contusional areas, preserved blood-brain barrier integrity and protected neurons. The mechanisms of DRP effects were attributable to reduction of the near-vessel wall cell-free layer which increased near-wall blood flow velocity, microcirculatory volume flow, and number of erythrocytes entering capillaries, thereby reducing capillary stasis and tissue hypoxia as reflected by a reduction in NADH. Our results indicate that early reduction in CBF after TBI is mainly due to ischemia; however, metabolic depression of contused tissue could be also involved.
创伤性脑损伤（TBI）后已明确证实存在脑缺血；然而，神经保护疗法尚未聚焦于改善脑微循环。由高分子量聚环氧乙烷制备的血液可溶性减阻聚合物（DRP），通过改变血液的流变学特性来靶向受损的微血管灌注，并且直到我们最近的报告之前，尚未应用于脑部。我们假设DRP可改善TBI后的脑微循环和氧合。在健康和创伤大鼠脑中研究了DRP，并与生理盐水对照组进行比较。通过在顶叶皮质进行体内双光子激光扫描显微镜检查，我们发现TBI后，纳摩尔浓度的血管内DRP显著增强了挫伤周围区域的微血管灌注和组织氧合，维持了血脑屏障的完整性并保护了神经元。DRP作用的机制归因于血管壁附近无细胞层的减少，这增加了近壁血流速度、微循环容积流量以及进入毛细血管的红细胞数量，从而减少了毛细血管淤滞和组织缺氧，这可通过NADH的减少反映出来。我们的结果表明，TBI后早期脑血流量减少主要是由于缺血；然而，挫伤组织的代谢抑制也可能起作用。
