Abstract Body: Introduction: Variations in light exposure are associated with changes in inflammation. The risk of thrombotic events such as ischemic stroke have been found to oscillate with the day-light cycle.

Aim: To investigate the impact of altering the light spectrum on ischemic stroke brain injury.

Methods: Mice were exposed to ambient (mice-white, 300lux), red light (mice-red, 617nm) or blue light (mice-blue, 442 nm) with 12:12 hour light:dark cycle for 72 hours. After 72 hours of light exposure, male and female mice were subjected to transient middle cerebral artery occlusion. Stroke outcomes were assessed at 24 hours.

Results: Exposure to long wavelength red light resulted in a significant reduction in infarct volume following stroke (mice-red 38.8±17.6 mm3 vs. mice-white 73.3±15.0 mm3; p<0.01 vs mice-blue 72.9±27.9 mm3; p<0.001). Red light exposure significantly improved neurological function compared to white and blue light exposure based on a modified Neurological Score (p<0.05). Furthermore, red light significantly improved motor function as measured by a reduced latency to turn and fall on a rotarod (p<0.05). The change in thrombosis only occurred when mice were pre-exposed to red light. Furthermore, red light had no effect on thrombosis in blind Vsx2^orJ/J mice. Red light exposure reduced platelet deposition in the brain while neutrophil levels were similar between light exposure groups. However, neutrophil extracellular traps (NETs) were significantly reduced (p<0.05) after ischemic stroke brain injury in mice exposued to red light. As platelets are known to activate neutrophils during ischemic stroke, we assessed the effect of red light on platelet function. Red light exposure reduced platelet aggregation (p=.02) and activation (p=.02). RNA-seq analysis demonstrated little transcriptomic changes between light exposed mice. However, red light exposure altered the platelet metabolome, suggesting red light altered platelet metabolism to effect platelet function. To examine if red light reduced platelet-dependent NET formation, releasate from activated platelets were incubated with neutrophils. Releasate from red light exposure platelets resulted in reduced NET formation (p=.03).

Conclusion: Exposure to long wavelength red light reduced ischemic stroke burden through a reduction in platelet-dependent NET formation. Light exposure modulation is a promising alternative for prophylaxis and treatment from ischemic stroke brain injury.