Abstract
Traumatic brain injury (TBI) ultimately leads to a reduction in the cerebral metabolic rate for oxygen due to ischemia. Previously, we showed that 2 ppm i.v. of drag-reducing polymers (DRP) improve hemodynamic and oxygen delivery to tissue in a rat model of mild-to-moderate TBI. Here we evaluated sex-specific and dose-dependent effects of DRP on microvascular CBF (mvCBF) and tissue oxygenation in rats after moderate TBI. In vivo two-photon laser scanning microscopy over the rat parietal cortex was used to monitor the effects of DRP on microvascular perfusion, tissue oxygenation, and blood-brain barrier (BBB) permeability. Lateral fluid-percussion TBI (1.5 ATA, 100 ms) was induced after baseline imaging and followed by 4 h of monitoring. DRP was injected at 1, 2, or 4 ppm within 30 min after TBI. Differences between groups were determined using a two-way ANOVA analysis for multiple comparisons and post hoc testing using the Mann-Whitney U test. Moderate TBI progressively decreased mvCBF, leading to tissue hypoxia and BBB degradation 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 and tissue oxygenation while protecting BBB in a dose-dependent manner without significant difference between males and females (p < 0.01). TBI resulted in an increase in intracranial pressure (20.1 ± 3.2 mmHg, p < 0.05), microcirculatory redistribution to non-nutritive microvascular shunt flow, and stagnation of capillary flow, all of which were dose-dependently mitigated by DRP. DRP at 4 ppm was most effective, with a non-significant trend to better outcomes in female rats.
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Supported by NIH R01NS112808.
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Bragin, D.E., Bragina, O.A., Kameneva, M.V., Trofimov, A.O., Nemoto, E.M. (2023). Sex-Specific and Dose-Dependent Effects of Drag-Reducing Polymers on Microcirculation and Tissue Oxygenation in Rats After Traumatic Brain Injury. In: Scholkmann, F., LaManna, J., Wolf, U. (eds) Oxygen Transport to Tissue XLIV. ISOTT 2022. Advances in Experimental Medicine and Biology, vol 1438. Springer, Cham. https://doi.org/10.1007/978-3-031-42003-0_13
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DOI: https://doi.org/10.1007/978-3-031-42003-0_13
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