Low‐level light emitting diode (LED) therapy suppresses inflammasome‐mediated brain damage in experimental ischemic stroke

• Published in: Journal of biophotonics Vol. 10; no. 11; pp. 1502 - 1513
• Main Authors: Lee, Hae In, Lee, Sae‐Won, Kim, Nam Gyun, Park, Kyoung‐Jun, Choi, Byung Tae, Shin, Yong‐Il, Shin, Hwa Kyoung
• Format: Journal Article
• Language: English
• Published: Weinheim WILEY‐VCH Verlag 01.11.2017; Wiley Subscription Services, Inc
• Subjects: Animals; Brain - metabolism; Brain - pathology; Brain - radiation effects; Brain damage; Brain injury; Brain Ischemia - complications; Cell activation; Cell death; Cell Death - radiation effects; Cytokines; Disease Models, Animal; Focal cerebral ischemia; Head injuries; Infiltration; Inflammasomes; Inflammasomes - metabolism; Inflammation; Interleukin 1; Interleukin 18; Ischemia; Levels; Light emitting diodes; Low-Level Light Therapy; MAP kinase; Mice; Microglia; Mitogen-Activated Protein Kinases - metabolism; neuroprotection; NF-κB protein; NLRP3; photostimulation; Rodents; Signaling; Stroke; Stroke - complications; Stroke - metabolism; Stroke - radiotherapy; Therapeutic applications; Therapy; TLR2; TLR2 protein; Toll-Like Receptor 2 - metabolism; Toll-like receptors; Focal cerebral ischemia; NLRP3; photostimulation; neuroprotection; TLR2
• ISSN: 1864-063X; 1864-0648
• DOI: 10.1002/jbio.201600244

Use of photostimulation including low‐level light emitting diode (LED) therapy has broadened greatly in recent years because it is compact, portable, and easy to use. Here, the effects of photostimulation by LED (610 nm) therapy on ischemic brain damage was investigated in mice in which treatment started after a stroke in a clinically relevant setting. The mice underwent LED therapy (20 min) twice a day for 3 days, commencing at 4 hours post‐ischemia. LED therapy group generated a significantly smaller infarct size and improvements in neurological function based on neurologic test score. LED therapy profoundly reduced neuroinflammatory responses including neutrophil infiltration and microglia activation in the ischemic cortex. LED therapy also decreased cell death and attenuated the NLRP3 inflammasome, in accordance with down‐regulation of pro‐inflammatory cytokines IL‐1β and IL‐18 in the ischemic brain. Moreover, the mice with post‐ischemic LED therapy showed suppressed TLR‐2 levels, MAPK signaling and NF‐kB activation. These findings suggest that by suppressing the inflammasome, LED therapy can attenuate neuroinflammatory responses and tissue damage following ischemic stroke. Therapeutic interventions targeting the inflammasome via photostimulation with LED may be a novel approach to ameliorate brain injury following ischemic stroke. Effect of post‐ischemic low‐level light emitting diode therapy (LED‐T) on infarct reduction was mediated by inflammasome suppression. This study identified a novel therapeutic mechanism in cases of ischemic damage that relies on suppressing neuroinflammation after the insult itself. Post‐ischemic low‐level light emitting diode (LED) therapy (LED‐T; 610 nm, 2 J/cm2) suppressed neuroinflammation and neural cell death in the ischemic cortex via TLR2‐mediated activation and the NLRP3 inflammasome, and that this activation was in turn mediated through MAPK and NF‐kB pathways. Notably, neurological scores were improved after LED therapy. Our findings suggest that therapeutic interventions targeting the inflammasome with LED would be beneficial to ameliorate brain injury following ischemic stroke. Effect of post‐ischemic low‐level light emitting diode therapy (LED‐T) on infarct reduction was mediated by inflammasome suppression.