Abstract TP275: Effect of Transcranial Laser and Thrombolytic Combination Therapy on Clinical Function and ATP Production in Small Clot Embolized Rabbits

Abstract

Background and Purpose: Transcranial laser therapy (TLT) and tissue plasminogen activator (tPA) improve behavior when administered following clot-induced strokes. tPA increases cerebral reperfusion and blood flow and TLT also enhances cerebral blood flow and activates mitochondrial function. We hypothesize that a combination therapy may be more effective than individual therapies and that efficacy may be mediated by enhancing mitochondrial function. Therefore, the goal of the present study is to evaluate the effect of combined TLT and tPA therapy on behavioral outcome and cellular ATP content using the rabbit small clot embolic stroke model (RSCEM). Methods: The study was conducted randomized and blinded. Male New Zealand white rabbits were embolized by injecting a suspension of small blood clots into brain via a carotid catheter. Using the RSCEM, we studied the effects of continuous wave TLT (7.5 mW/cm2, 2 minutes) alone or in combination with standardized intravenous (IV) tPA (3.3mg/kg) applied 1 hour post-embolization on 3 endpoints: 1) behavioral function measured 2 days [effective stroke dose (P50 in mg) producing neurological deficits in 50% of embolized rabbits], 2) intracerebral hemorrhage (ICH) rate, and 3) cortical adenosine-5'-triphosphate (ATP) content was measured 6 hours following embolization. Results: TLT and tPA significantly (p<0.05) increased P50 values by 95% (p=0.026) and 56% (p=0.026) over control, respectively. TLT-tPA increased P50 by 136% over control (p=0.0038 compared to control). Treatment did not affect ICH incidence. Embolization reduced cortical ATP content by 39%; decreases that were attenuated by both TLT and tPA treatment (p<0.05). TLT-tPA further enhanced cortical ATP levels 22% above that measured in naïve control. Conclusion: TLT and tPA both effectively and safely improve behavioral outcome in embolized rabbits and attenuate stroke-induced ATP deficits; TLT-tPA did not offer additional clinical benefit, but the TLT-tPA combination produced a synergistic effect on ATP levels. The study suggests that tPA-induced reperfusion in combination with TLT neuroprotection therapy may optimally protect viable cells in the cortex measured using ATP levels as a marker.