Rheological effects of drag-reducing polymers improve cerebral blood flow and oxygenation after traumatic brain injury in rats

Abstract

Cerebral ischemia has been clearly demonstrated after traumatic brain injury (TBI); however, neuroprotective therapies have not focused on improvement of the cerebral microcirculation. Blood soluble drag-reducing polymers (DRP), prepared from high molecular weight polyethylene oxide, target impaired microvascular perfusion by altering the rheological properties of blood and, until our recent reports, has not been applied to the brain. We hypothesized that DRP improve cerebral microcirculation and oxygenation after TBI. DRP were studied in healthy and traumatized rat brains and compared to saline controls. Using in-vivo two-photon laser scanning microscopy over the parietal cortex, we showed that after TBI, nanomolar concentrations of intravascular DRP significantly enhanced microvascular perfusion and tissue oxygenation in peri-contusional areas, preserved blood-brain barrier integrity and protected neurons. The mechanisms of DRP effects were attributable to reduction of the near-vessel wall cell-free layer which increased near-wall blood flow velocity, microcirculatory volume flow, and number of erythrocytes entering capillaries, thereby reducing capillary stasis and tissue hypoxia as reflected by a reduction in NADH. Our results indicate that early reduction in CBF after TBI is mainly due to ischemia; however, metabolic depression of contused tissue could be also involved.

Resuscitation Fluid with Drag Reducing Polymer Enhances Cerebral Microcirculation and Tissue Oxygenation After Traumatic Brain Injury Complicated by Hemorrhagic Shock

“…In the peri-contusion area after TBI, microvascular CBF, measured by in-vivo 2PLSM showed a reduction in capillary flow velocity to 0.59 ± 0.03 mm/s from 0.77± 0.05 mm/s and about ~25% reduction in the number of functioning capillaries due to microthrombosis leading to tissue hypoxia, reflected by a ~25% increase in NADH autofluorescence (Fig. 1; P < 0.05 from baseline) which agrees with our previous observations [5]. …”

“…Based on our data and previous studies [5,8], the mechanisms of restoring mvCBF by DRP-RF include increasing the arteriolar blood volume flow via the increase of flow velocity by reduction of flow separations and vortices at vessel bifurcations and decreasing pressure loss across the arterial network due to the viscoelastic properties of DRP. This leads to a rise in the pre-capillary blood pressure thus enhancing capillary perfusion, countering capillary stasis, increasing the density of functioning capillaries and the number of RBC passing through capillaries to improve tissue oxygenation.…”

“…Most of the procedures used in these studies we described previously [5]. Protocol #200640 was approved by the Institutional Animal Care and Use Committee of the University of New Mexico and the studies were conducted according the NIH Guide for the Care and Use of Laboratory Animals.…”

“…Images (512 × 512 pixels, 0.15 um/pixel in the x- and y-axes) or line scans were acquired using Prairie View software. Red blood cell flow velocity was measured in microvessels ranging from 3-50 µm diameter up to 500 µm below the surface of the parietal cortex, as described previously [5]. Tissue hypoxia was assessed by measurement of NADH autofluorescence.…”

Platelet‐derived extracellular vesicles released after trauma promote hemostasis and contribute to DVT in mice

“…It remains unexplored how the response of activated platelets and PEVs alters the dynamics of blood flow following injury. The rheology of blood flow following injury and hemorrhage has been previously investigated, 44 and preservation of the cell-free layer has been shown to be critical for glycocalyx and endothelial integrity. 45 Although the role of tissue factor bearing tumor microparticles has been previously implicated in cancer associated VTE, the potential contribution of PEVs to thrombosis following injury was previously unexplored.…”