Taking a light approach to treating acute ischemic stroke patients: transcranial near-infrared laser therapy translational science

Abstract

Transcranial near-infrared laser therapy (NILT) has been investigated as a novel neuroprotective treatment for acute ischemic stroke (AIS), for approximately 10 years. Two clinical trials, NeuroThera Effectiveness and Safety Trial (NEST)-1 and NEST-2, have evaluated the use of NILT to promote clinical recovery in patients with AIS. This review covers preclinical, translational, and clinical studies documented during the period 1997-2010. The primary aim of this article is to detail the development profile of NILT to treat AIS. Secondly, insight into possible mechanisms involved in light therapy will be presented. Lastly, possible new directions that should be considered to improve the efficacy profile of NILT in AIS patients will be discussed. The use of NILT was advanced to clinical trials based upon extensive translational research using multiple species. NILT, which may promote functional and behavioral recovery via a mitochondrial mechanism and by enhancing cerebral blood flow, may eventually be established as an Food and Drug Administration (FDA)-approved treatment for stroke. The NEST-3 trial, which is the pivotal trial for FDA approval, should incorporate hypotheses derived from translational studies to ensure efficacy in patients. Future NILT studies should consider administration of a thrombolytic to enhance cerebral reperfusion alongside NILT neuroprotection.

Conflict of interest statement

Declaration of interest: This work was supported by a U01 Translational research grant NS060685 to Paul Lapchak.

Figures

Figure 1. Correlation between Power Density, Behavioral Improvement and Cortical ATP

Panel A provides data for a correlation between Energy Density and Cortical ATP content measured following embolic strokes. The curve is biphasic showing a steep slope up to 4.5 J/cm2, and a shallow slope thereafter. As extrapolated value of 2.86 J/cm2 was calculated for “normalization” of ATP content to 100% of control(37); Panel B shows the correlation between Energy density and Behavioral Improvement. The data shows that a threshold Energy Density above equal to or above 0.9 J/cm2 is required to produce a significant (*p<0.05) increase in P50 values (Clot dose or burden in brain measured in mg that produces abnormality in 50% of the population) following an embolic stroke (24, 46).

Figure 2. NILT Therapeutic Window Analysis in Rabbits Following Embolic Strokes

Therapeutic window for Continuous Wave (CW) NILT induced clinical improvement in small clot embolized rabbits. Data is shown as Clinical Improvement (% Increase) as a function of NILT treatment time (initiation post embolization). The beneficial effect of NILT is statistically significant (*p

Figure 3. NILT Development Profile to Treat Stroke

Complete development profile for NILT to treat AIS from concept to multiple Phase 3 clinical trials supported by translational research studies in multiple preclinical stroke models. RSCEM- Rabbit small clot embolic stroke model; RLCEM- Rabbit large clot embolic stroke model. Citations are in brackets.