Pre-conditioning with transcranial low-level light therapy reduces neuroinflammation and protects blood-brain barrier after focal cerebral ischemia in mice

Article type: Research Article

Authors: Lee, Hae In^a | Park, Jung Hwa^b | Park, Min Young^b | Kim, Nam Gyun^c | Park, Kyoung-Jun^c | Choi, Byung Tae^{b; d; e} | Shin, Yong-II^{a; f; 1; *} | Shin, Hwa Kyoung^{b; d; e; 1; *}

Affiliations: [a] Department of Rehabilitation Medicine, School of Medicine, Pusan National University, Yangsan, Gyeongnam, Republic of Korea | [b] Department of Korean Medical Science, School of Korean Medicine, Pusan National University, Yangsan, Gyeongnam, Republic of Korea | [c] Medical Research Center of Color Seven, Seoul, Republic of Korea | [d] Division of Meridian and Structural Medicine, School of Korean Medicine, Pusan National University, Yangsan, Gyeongnam, Republic of Korea | [e] Korean Medical Science Research Center for Healthy-Aging, Pusan National University, Yangsan, Gyeongnam, Republic of Korea | [f] Research Institute for Convergence of Biomedical Science and Technology, Pusan National UniversityYangsan Hospital, Yangsan, Gyeongnam, Republic of Korea

Correspondence: [*] Corresponding author: Hwa Kyoung Shin, Ph.D. and Yong-II Shin, M.D., Ph.D. Department of Korean Medical Science, School of Korean Medicine, Pusan National University, Yangsan, Gyeongnam 626-870, Republic of Korea and Department of Rehabilitation Medicine, School of Medicine, Pusan National University, Yangsan, Gyeongnam 626-870, Republic of Korea. Tel.: +82 51 510 8476; Fax: +82 51 510 8437; E-mails: [email protected]; [email protected].

Note: [1] These authors contributed equally to this work.

Abstract: Purpose: Transcranial low-level light therapy (LLLT) has gained interest as a non-invasive, inexpensive and safe method of modulating neurological and psychological functions in recent years. This study was designed to examine the preventive effects of LLLT via visible light source against cerebral ischemia at the behavioral, structural and neurochemical levels. Methods: The mice received LLLT twice a day for 2 days prior to photothrombotic cortical ischemia. Results: LLLT significantly reduced infarct size and edema and improved neurological and motor function 24 h after ischemic injury. In addition, LLLT markedly inhibited Iba-1- and GFAP-positive cells, which was accompanied by a reduction in the expression of inflammatory mediators and inhibition of MAPK activation and NF-κB translocation in the ischemic cortex. Concomitantly, LLLT significantly attenuated leukocyte accumulation and infiltration into the infarct perifocal region. LLLT also prevented BBB disruption after ischemic events, as indicated by a reduction of Evans blue leakage and water content. These findings were corroborated by immunofluorescence staining of the tight junction-related proteins in the ischemic cortex in response to LLLT. Conclusions: Non-invasive intervention of LLLT in ischemic brain injury may provide a significant functional benefit with an underlying mechanism possibly being suppression of neuroinflammation and reduction of BBB disruption.

Keywords: Low-level light therapy, focal cerebral ischemia, blood-brain barrier, neuroinflammation

DOI: 10.3233/RNN-150559

Journal: Restorative Neurology and Neuroscience, vol. 34, no. 2, pp. 201-214, 2016