title: Pretreatment with light-emitting diode therapy reduces ischemic brain injury in mice through endothelial nitric oxide synthase-dependent mechanisms.
abstract: 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.
authors.affiliation: Department of Rehabilitation Medicine, School of Medicine, Pusan National University, Yangsan, Gyeongnam 50612, Republic of Korea; Research Institute for Convergence of Biomedical Science and Technology, Pusan National University Yangsan Hospital, Yangsan, Gyeongnam 50612, Republic of Korea.
authors.forename: Hae In
authors.initials: HI
authors.lastname: Lee
authors.affiliation: Department of Korean Medical Science, School of Korean Medicine, Pusan National University, Yangsan, Gyeongnam 50612, Republic of Korea; Graduate Training Program of Korean Medicine for Healthy-Aging, Pusan National University, Yangsan, Gyeongnam 50612, Republic of Korea; Korean Medical Science Research Center for Healthy-Aging, Pusan National University, Yangsan, Gyeongnam 50612, Republic of Korea.
authors.forename: Sae-Won
authors.initials: SW
authors.lastname: Lee
authors.affiliation: Korean Medical Science Research Center for Healthy-Aging, Pusan National University, Yangsan, Gyeongnam 50612, Republic of Korea.
authors.forename: So Young
authors.initials: SY
authors.lastname: Kim
authors.affiliation: Medical Research Center of Color Seven, Seoul 06719, Republic of Korea.
authors.forename: Nam Gyun
authors.initials: NG
authors.lastname: Kim
authors.affiliation: Medical Research Center of Color Seven, Seoul 06719, Republic of Korea.
authors.forename: Kyoung-Jun
authors.initials: KJ
authors.lastname: Park
authors.affiliation: Department of Korean Medical Science, School of Korean Medicine, Pusan National University, Yangsan, Gyeongnam 50612, Republic of Korea; Graduate Training Program of Korean Medicine for Healthy-Aging, Pusan National University, Yangsan, Gyeongnam 50612, Republic of Korea; Korean Medical Science Research Center for Healthy-Aging, Pusan National University, Yangsan, Gyeongnam 50612, Republic of Korea.
authors.forename: Byung Tae
authors.initials: BT
authors.lastname: Choi
authors.affiliation: Department of Rehabilitation Medicine, School of Medicine, Pusan National University, Yangsan, Gyeongnam 50612, Republic of Korea; Research Institute for Convergence of Biomedical Science and Technology, Pusan National University Yangsan Hospital, Yangsan, Gyeongnam 50612, Republic of Korea. Electronic address: rmshin01@gmail.com.
authors.forename: Yong-Il
authors.initials: YI
authors.lastname: Shin
authors.affiliation: Department of Korean Medical Science, School of Korean Medicine, Pusan National University, Yangsan, Gyeongnam 50612, Republic of Korea; Graduate Training Program of Korean Medicine for Healthy-Aging, Pusan National University, Yangsan, Gyeongnam 50612, Republic of Korea; Korean Medical Science Research Center for Healthy-Aging, Pusan National University, Yangsan, Gyeongnam 50612, Republic of Korea. Electronic address: julie@pusan.ac.kr.
authors.forename: Hwa Kyoung
authors.initials: HK
authors.lastname: Shin
mesh_terms: D000818:Animals; D001930:Brain Injuries / Q000201:enzymology* / Q000209:etiology / Q000628:therapy*; D002545:Brain Ischemia / Q000150:complications / Q000175:diagnosis / Q000201:enzymology* / Q000628:therapy*; D008027:Light; D008029:Lighting / Q000295:instrumentation / Q000379:methods; D008297:Male; D051379:Mice; D008810:Mice, Inbred C57BL; D052250:Nitric Oxide Synthase Type III / Q000378:metabolism*; D010789:Phototherapy / Q000295:instrumentation* / Q000379:methods; D011300:Preoperative Care / Q000379:methods; D011829:Radiation Dosage; D012666:Semiconductors; D016896:Treatment Outcome
chemical_list: D052250:Nitric Oxide Synthase Type III; C496315:Nos3 protein, mouse
keywords: Cerebral blood flow; Endothelial nitric oxide synthase; Focal cerebral ischemia; Vascular dysfunction; eNOS-deficient mice