(1534) Drag-Reducing Polymers in the Treatment of Severe Traumatic Brain Injury

Introduction: Traumatic brain injury ultimately leads to a reduction in cerebral metabolic rate for oxygen due to ischemia and/or metabolic depression. An increasing body of evidence suggests that cerebral blood flow differs between males and females in the intact and injured brain. Previously, we showed that two ppm of drag-reducing polymers (DRPs) in blood improve hemodynamic and oxygen delivery to tissue in a rat model of mild-to-moderate traumatic brain injury (TBI).

Aim: To evaluate sex-specific and dose-dependent effects of drag-reducing polymers on microcirculation and tissue oxygenation in rats after severe traumatic brain injury.

Methods: In-vivo two-photon laser scanning microscopy over the rat parietal cortex was used to monitor the effects of DRPs on microvascular perfusion, tissue oxygenation (NADH) and blood-brain barrier permeability. Brain and rectal temperatures, MAP, blood gases and electrolytes were monitored. Lateral fluid-percussion TBI (2.5 ATA, 100 ms) was induced after baseline imaging and followed by 4 hours of monitoring. DRPs were injected at 1, 2, or 4 ppm within 30 minutes after TBI induction. Data analysis was done by GraphPad Prism 7. Differences between groups were determined using a two-way ANOVA analysis for multiple comparisons and post hoc testing.

Results: The severe TBI resulted in an intracranial pressure increase (31±3.2 mmHg, p< 0.05), leading to microcirculation redistribution to non-nutritive microvascular shunt (MVS) flow and stagnation of capillary flow. Microcirculation impairment led to tissue hypoxia and blood-brain barrier (BBB) degradation, more prominent in male rats. DRPs, improved cerebral microcirculation, reduced intracranial hypertension, tissue hypoxia and BBB degradation in a dose-related manner with better efficiency in females (p < 0.01).

Conclusions: DRP at 4 ppm was most efficient, with better effects in female rats. Supported by NIH/NINDS R01NS112808.