Improvement of Impaired Cerebral Microcirculation Using Rheological Modulation by Drag-Reducing Polymers

Abstract

Nanomolar intravascular concentrations of drag-reducing polymers (DRP) have been shown to improve hemodynamics and survival in animal models of ischemic myocardium and limb, but the effects of DRP on the cerebral microcirculation have not yet been studied. We recently demonstrated that DRP enhance microvascular flow in normal rat brain and hypothesized that it would restore impaired microvascular perfusion and improve outcomes after focal ischemia and traumatic brain injury (TBI). We studied the effects of DRP (high molecular weight polyethylene oxide, 4,000 kDa, i.v. at 2 µg/mL of blood) on microcirculation of the rat brain: 1) after permanent middle cerebral artery occlusion (pMCAO); and 2) after TBI induced by fluid percussion. Using in-vivo two-photon laser scanning microscopy (2PLSM) over the parietal cortex of anesthetized rats we showed that both pMCAO and TBI resulted in progressive decrease in microvascular circulation, leading to tissue hypoxia (NADH increase) and increased blood brain barrier (BBB) degradation. DRP, injected post insult, increased blood volume flow in arterioles and red blood cell (RBC) flow velocity in capillaries mitigating capillary stasis, tissue hypoxia and BBB degradation, which improved neuronal survival (Fluoro-Jade B, 24 hours) and neurologic outcome (Rotarod, 1 week). Improved microvascular perfusion by DRP may be effective in the treatment of ischemic stroke and TBI.

Cerebral Microvascular Injury: A Potentially Treatable Endophenotype of Traumatic Brain Injury-Induced Neurodegeneration

“…Injury-induced decreases in CBF and microvascular circulation can result in microthrombus formation (Schwarzmaier et al, 2016) and tissue hypoxia (Bragin et al, 2016). Compared with sham animals, animals exposed to CCI had a greater incidence of stationary leukocyte-platelet aggregates in parenchymal capillaries (Schwarzmaier et al, 2016).…”