Resuscitation with drag reducing polymers after traumatic brain injury with hemorrhagic shock reduces microthrombosis and oxidative stress

Abstract

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.