Rheological effects of drag-reducing polymers improve cerebral blood flow and oxygenation after traumatic brain injury in rats
Rheological effects of drag-reducing polymers improve cerebral blood flow and oxygenation after traumatic brain injury in rats
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DOI：
10.1177/0271678x16684153
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发表时间：
2017-03-01
影响因子：
6.3
通讯作者：
Nemoto, Edwin M.
中科院分区：
文献类型：
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作者：
Bragin, Denis E.;Kameneva, Marina V.;Nemoto, Edwin M.
创伤性脑损伤（TBI）后明显存在脑缺血；然而，神经保护疗法并未侧重于改善大脑微循环。由高分子量聚乙烯氧化物制备的血溶性减阻聚合物（DRP），通过改变血液的流变特性来靶向受损的微血管灌注，直到我们最近的报道，还没有应用于大脑。我们假设DRP改善脑外伤后的大脑微循环和氧合。在健康和创伤大鼠大脑中研究DRP，并与生理盐水对照进行比较。通过在顶叶皮层上的活体双光子激光扫描显微镜，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，保持了血脑屏障的完整性和保护了神经元。DRP作用的机制是由于近血管壁无细胞层的减少，增加了近壁血流速度、微循环容积流量和进入毛细血管的红细胞数量，从而减少了毛细血管停滞和组织缺氧，体现在NADH的减少上。我们的研究结果表明，脑外伤后早期脑血流减少主要是由于缺血；然而，挫伤组织的代谢抑制也可能涉及。
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.