Dose-finding study of phototherapy on stroke outcome in a rabbit model of ischemic stroke

Abstract

GoalWhile transcranial laser therapy (TLT) has been shown to improve clinical outcome in a preclinical model of ischemic stroke, optimal timing and dosing has yet to be tested adequately. The purpose of this study was to assess clinical stroke outcome in the Rabbit Small Clot Embolic Model (RSCEM) with dose escalating TLT. MethodsWe utilized the rabbit small clot embolic stroke model (RSCEM) using dose-escalating regimens. Behavioral analysis was conducted at 24h post-embolization, allowing for the determination of the effective stroke dose (ES50) or clot amount (mg) that produces neurological deficits in 50% of a group of rabbits. Using the RSCEM, a treatment is considered beneficial if it significantly increases the ES50 compared with the control group. FindingsA significant behavioral benefit was seen at triple TLT of 111mW treatment of 2min at 2h post-embolization (6.47±1.06, n=17; p=0.03), compared with the previously used regimen (3.09±0.51, n=15). ConclusionTLT results in significant behavioral improvement when administered 2h post-embolization. Studies are warranted to evaluate this therapy in combination with thrombolysis.