Pretreatment with light-emitting diode therapy reduces ischemic brain injury in mice through endothelial nitric oxide synthase-dependent mechanisms

• Published in: Biochemical and biophysical research communications Vol. 486; no. 4; pp. 945 - 950
• Main Authors: Lee, Hae In, Lee, Sae-Won, Kim, So Young, Kim, Nam Gyun, Park, Kyoung-Jun, Choi, Byung Tae, Shin, Yong-Il, Shin, Hwa Kyoung
• Format: Journal Article
• Language: English
• Published: United States Elsevier Inc 13.05.2017
• Subjects: Animals; Brain Injuries - enzymology; Brain Injuries - etiology; Brain Injuries - therapy; Brain Ischemia - complications; Brain Ischemia - diagnosis; Brain Ischemia - enzymology; Brain Ischemia - therapy; Cerebral blood flow; Endothelial nitric oxide synthase; eNOS-deficient mice; Focal cerebral ischemia; Light; Lighting - instrumentation; Lighting - methods; Male; Mice; Mice, Inbred C57BL; Nitric Oxide Synthase Type III - metabolism; Phototherapy - instrumentation; Phototherapy - methods; Preoperative Care - methods; Radiation Dosage; Semiconductors; Treatment Outcome; Vascular dysfunction; Focal cerebral ischemia; Endothelial nitric oxide synthase; Vascular dysfunction; eNOS-deficient mice; Cerebral blood flow
• ISSN: 0006-291X; 1090-2104
• DOI: 10.1016/j.bbrc.2017.03.131

Photostimulation with low-level light emitting diode therapy (LED-T) modulates neurological and psychological functions. The purpose of this study was to evaluate the effects of LED-T pretreatment on the mouse brain after ischemia/reperfusion and to investigate the underlying mechanisms. Ischemia/reperfusion brain injury was induced by middle cerebral artery occlusion. The mice received LED-T twice a day for 2 days prior to cerebral ischemia. After reperfusion, the LED-T group showed significantly smaller infarct and edema volumes, fewer behavioral deficits compared to injured mice that did not receive LED-T and significantly higher cerebral blood flow compared to the vehicle group. We observed lower levels of endothelial nitric oxide synthase (eNOS) phosphorylation in the injured mouse brains, but significantly higher eNOS phosphorylation in LED-T-pretreated mice. The enhanced phospho-eNOS was inhibited by LY294002, indicating that the effects of LED-T on the ischemic brain could be attributed to the upregulation of eNOS phosphorylation through the phosphoinositide 3-kinase (PI3K)/Akt pathway. Moreover, no reductions in infarct or edema volume were observed in LED-T-pretreated eNOS-deficient (eNOS–/–) mice. Collectively, we found that pretreatment with LED-T reduced the amount of ischemia-induced brain damage. Importantly, we revealed that these effects were mediated by the stimulation of eNOS phosphorylation via the PI3K/Akt pathway. •Mice pretreated with LED-T had less brain damage and fewer behavioral deficits after ischemic injury.•Mice pretreated with LED-T displayed higher cerebral blood flow after ischemia.•Mice pretreated with LED-T had higher eNOS phosphorylation through the PI3K/Akt pathway after focal cerebral ischemia.•LED-T pretreatment did not reduce brain damage in eNOS–/– mice.