Abstract TP291: Near-Infrared II Photobiomodulation Protects Against Stroke via Endothelial Nitric Oxide Phosphorylation

Abstract

Since endothelial dysfunction is implicated in stroke pathogenesis and is featured with suppressed endothelial nitric oxide (NO) synthase (eNOS) and NO deficiency, restoring endothelial NO represents a promising approach to treating stroke injury. We have shown that near-infrared II (NIR-II) laser treatment enhances the phosphorylation of eNOS at serine 1176 (S1176) and augments NO production. Here, we further determine the beneficial effect of NIR-II laser on stroke injury. Wild-type (WT) C57BL/6J and unphosphorylatable eNOS mutant mice with S1176A mutation (S1176A) were treated by NIR-II laser (1064 nm) at an irradiance of 50 mW/cm2 (5 min daily for 4 days) prior to the middle cerebral artery occlusion (MCAO, 30 min) by a filament. The ischemic and reperfusion (30 min) values of cerebral blood flow (CBF) were confirmed by laser Doppler flowmetry. Neurological deficit and infarct volume was evaluated 48 h after reperfusion. One- and two-way ANOVAs and the Kruskal-Wallis followed by Dunn's tests were used for statistical evaluation. The NIR-II laser-pretreated WT mice demonstrated significantly increased CBF reperfusion and decreased infarct volume compared with untreated mice. The neurologic scoring showed less severe deficits in the laser-treated mice than in the non-treated mice (1.1 vs. 1.8). To determine the involvement of S1176-dependent eNOS phosphorylation in NIR-II effects, we further treated S1176A mice. MCAO followed by reperfusion resulted in decreased CBF and an increased infarct volume in S1176A mice compared to WT mice. The infarct volume was significantly larger in laser-treated S1176A compared to laser-treated WT mice. Neurological deficit in S1176A mice showed no improvement with the laser pretreatment (2.3 vs. 2.6) and was significantly more severe in the laser-treated S1176A compared to the laser-treated WT mice. In conclusion, pretreatment with a 1064 nm laser at 50 mW/cm2 improved stroke outcomes via S1176 eNOS phosphorylation. NIR-II photobiomodulation offers a non-invasive and low-risk treatment for stroke. This new modality using a physical parameter could lead to the development of innovative therapies to prevent and treat a wide array of cerebrovascular diseases.