Abstract WMP118: Sex-specific And Dose-dependent Effects Of Drag-reducing Polymers On Post-traumatic Ischemia In Rats After Traumatic Brain Injury Of Different Severity

Abstract

Introduction: Previously, we showed that drag-reducing polymers (DRP) improve hemodynamics in rat models of brain injury (TBI). Here we examined the dose- and sex-dependent DRP effects on post-TBI ischemia. Methods: In-vivo 2-photon microscopy over the rat parietal cortex was used to monitor the effect of DRP on microvascular perfusion and tissue oxygenation (NADH) and blood-brain barrier permeability. Lateral fluid-percussion TBI (1.5 ATA-moderate or 2.5 ATA-severe, 100 ms) was induced after baseline imaging and followed by 4 hours of monitoring. DRP injected at 1, 2, or 4 ppm. Data analysis was done by GraphPad Prism 7. Results: Moderate TBI progressively decreased microvascular circulation and hypoxia in the pericontusion zone (p<0.05). The i.v. injection of DRP increased near-wall flow velocity and flow rate in arterioles, leading to an increase in the number of erythrocytes entering capillaries, enhancing capillary perfusion in a dose-dependent manner without distinguishable difference between males and females (p<0.01). The severe TBI resulted in 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. Tissue hypoxia was more prominent, especially in male rats; the pericontusion zone was 25±5.2% larger than after moderate TBI (p<0.01). Both were reverted by DRP in a dose-related manner with better efficiency in females (p<0.01). After severe TBI, BBB degradation was faster and more prominent. DRP was more efficient in attenuating the progression of permeability increase in moderate TBI (p<0.05). Conclusion: DRP at 4 ppm was most efficient, with a better effect on female rats. Supported by NIH/NINDS R01NS112808