Abstract W P93: Drag-Reducing Polymer Improves Microcirculation and Outcome after Permanent Middle Cerebral Artery Occlusion in Rats

Abstract

Introduction: Current treatments for ischemia after stroke have not focused directly on the physiological effects of restoring or improving cerebral microvascular perfusion. Nanomolar concentrations of drag-reducing polymers (DRP) have been shown to improve hemodynamics and survival in animal models of the ischemic myocardium and peripheral circulation. We recently demonstrated that DRP improved microvascular perfusion in normal and traumatized rat brain. We hypothesized that DRP restores microvascular perfusion after focal ischemia and improves neurologic recovery in the rat. Methods: The suture permanent middle cerebral artery occlusion (MCAO) model in the rat was used. DRP was injected i.v. 90 minutes after MCAO. Controls were injected with an equal volume of saline. Using in vivo 2-photon laser scanning microscopy over the parietal cortex, we studied the acute effects of DRP on microvascular blood flow velocity, tissue oxygenation (NADH) and blood brain barrier (BBB) permeability for 5 hr after MCAO. Doppler cortical flow, rectal and cranial temperatures, arterial pressure, blood gases and electrolytes were monitored. Cerebral infarction was evaluated by triphenyltetrazolium chloride (TTC) staining 24 hr after MCAO and motor function by Rotarod at one week. Results: MCAO resulted in a progressive decrease in microvascular flow in the penumbra of the parietal cortex with hypoxia and increased BBB permeability during 5 hr monitored. DRP partially restored microvascular flow compared to control (21±6.7%, Mean ± SEM, p<0.05, n=4) and reduced the progression of ischemia and BBB permeability by 14±4.6 and 18±6.5%, respectively (p<0.05). Infarction volume was reduced by 24±8.1% in DRP treated rats (n=2, p<0.05). The Rotarod tests showed that one week after MCAO, DRP treated rats performed better than saline treated rats with times of 75.6±16.0% and 47.3±16.0%, respectively, as percent of normal rats. Conclusions: DRP restores cerebral microvascular flow after MCAO reducing tissue hypoxia and BBB damage. The improvement in flow is reflected by a reduction in infarct size 24 hours after MCAO and by improved motor neurological recovery at one week after MCAO. DRP can be a new effective therapy for ischemic stroke targeting microvascular perfusion.