Department of Neurosurgery, University of New Mexico School of Medicine, Albuquerque, NM, USA.
McGowan Institute for Regenerative Medicine, University of Pittsburgh, Pittsburgh, NM, USA.
Adv Exp Med Biol. 2020;1232:39-45. doi: 10.1007/978-3-030-34461-0_6.
Outcome after traumatic brain injury (TBI) is worsened by hemorrhagic shock (HS); however, the existing volume expansion approach with resuscitation fluids (RF) is controversial as it does not adequately alleviate impaired microvascular cerebral blood flow (mCBF). We previously reported that resuscitation fluid with drag reducing polymers (DRP-RF) improves CBF by rheological modulation of hemodynamics. Here, we evaluate the efficacy of DRP-RF, compared to lactated Ringers resuscitation fluid (LR-RF), in reducing cerebral microthrombosis and reperfusion mitochondrial oxidative stress after TBI complicated by HS. Fluid percussion TBI (1.5 ATA, 50 ms) was induced in rats and followed by controlled HS to a mean arterial pressure (MAP) of 40 mmHg. DRP-RF or LR-RF was infused to restore MAP to 60 mmHg for 1 h (pre-hospital period), followed by blood re-infusion to a MAP = 70 mmHg (hospital period). In vivo 2-photon laser scanning microscopy over the parietal cortex was used to monitor microvascular blood flow, nicotinamide adenine dinucleotide (NADH) for tissue oxygen supply and mitochondrial oxidative stress (superoxide by i.v. hydroethidine [HEt], 1 mg/kg) for 4 h after TBI/HS, followed by Dil vascular painting during perfusion-fixation. TBI/HS decreased mCBF resulting in capillary microthrombosis and tissue hypoxia. Microvascular CBF and tissue oxygenation were significantly improved in the DRP-RF compared to the LR-RF treated group (p < 0.05). Reperfusion-induced oxidative stress, reflected by HEt fluorescence, was 32 ± 6% higher in LR-RF vs. DRP-RF (p < 0.05). Post-mortem whole-brain visualization of DiI painted vessels revealed multiple microthromboses in both hemispheres that were 29 ± 3% less in DRP-RF vs. LR-RF group (p < 0.05). Resuscitation after TBI/HS using DRP-RF effectively restores mCBF, reduces hypoxia, microthrombosis formation, and mitochondrial oxidative stress compared to conventional volume expansion with LR-RF.
创伤性脑损伤（TBI）后的预后因出血性休克（HS）而恶化；然而，现有的用复苏液（RF）进行容量扩充的方法存在争议，因为它不能充分缓解受损的微血管脑血流（mCBF）。我们之前曾报道过，用减阻聚合物（DRP）制成的复苏液可通过血流动力学的流变调节来改善 CBF。在这里，我们评估了 DRP-RF 与乳酸林格氏液（LR-RF）相比，在减轻 TBI 合并 HS 后脑微血栓形成和再灌注线粒体氧化应激方面的疗效。在大鼠中诱导液体冲击性 TBI（1.5 ATA，50 ms），然后将其控制为平均动脉压（MAP）为 40 mmHg 的 HS。DRP-RF 或 LR-RF 用于将 MAP 恢复至 60 mmHg 1 小时（院前期），然后再将 MAP 恢复至 70 mmHg （医院期）。在 TBI/HS 后 4 小时，使用颅顶皮层的活体双光子激光扫描显微镜监测微血管血流、烟酰胺腺嘌呤二核苷酸（NADH）以供应组织氧和线粒体氧化应激（通过静脉内羟乙基噻吩[HEt]，1 mg/kg），然后在灌注固定期间进行 Dil 血管染色。TBI/HS 降低了 mCBF，导致毛细血管微血栓形成和组织缺氧。与 LR-RF 治疗组相比，DRP-RF 显著改善了微血管 CBF 和组织氧合（p < 0.05）。再灌注诱导的氧化应激，反映在 HEt 荧光中，在 LR-RF 中比在 DRP-RF 中高 32 ± 6%（p < 0.05）。DiI 染色血管的死后全脑可视化显示，两个半球均有多处微血栓形成，DRP-RF 组比 LR-RF 组少 29 ± 3%（p < 0.05）。与常规用 LR-RF 进行容量扩充相比，TBI/HS 后使用 DRP-RF 进行复苏可有效恢复 mCBF，减轻缺氧、微血栓形成形成和线粒体氧化应激。
