Near-Infrared II Photobiomodulation Preconditioning Ameliorates Stroke Injury via Phosphorylation of eNOS

Author:

Yokomizo Shinya12ORCID,Kopp Timo34ORCID,Roessing Malte34,Morita Atsuyo3,Lee Seeun56ORCID,Cho Suin56ORCID,Ogawa Emiyu7,Komai Eri3ORCID,Inoue Kazumasa2ORCID,Fukushi Masahiro2,Feil Susanne4ORCID,Kim Hyung-Hwan5ORCID,Bragin Denis E.89ORCID,Gerashchenko Dmitry10ORCID,Huang Paul L.3ORCID,Kashiwagi Satoshi1110ORCID,Atochin Dmitriy N.310ORCID

Affiliation:

1. Department of Neurology, MassGeneral Institute of Neurodegenerative Diseases (S.Y.), Massachusetts General Hospital and Harvard Medical School, Charlestown.

2. Department of Radiological Science, Tokyo Metropolitan University, Japan (S.Y., K.I., M.F.).

3. Cardiovascular Research Center, Department of Medicine (T.K., M.R., A.M., E.K., P.L.H., D.N.A.), Massachusetts General Hospital and Harvard Medical School, Charlestown.

4. Interfaculty Institute of Biochemistry, University of Tübingen, Germany (T.K., M.R., S.F.).

5. Stroke and Neurovascular Regulation Laboratory, Department of Radiology, Massachusetts General Hospital and Harvard Medical School, Charlestown (S.L., S.C., H.-H.K.).

6. School of Korean Medicine, Pusan National University, Yangsan, Republic of Korea (S.L., S.C.).

7. School of Allied Health Science, Kitasato University, Kanagawa, Japan (E.O.).

8. Lovelace Biomedical Research Institute, Albuquerque, NM (D.E.B.).

9. Department of Neurology, The University of New Mexico School of Medicine, Albuquerque, NM (D.E.B.).

10. Department of Psychiatry, Boston VA Medical Center West Roxbury, Veterans Affairs Boston Healthcare System and Harvard Medical School, MA (D.G., S.K., D.N.A.).

11. Gordon Center for Medical Imaging, Department of Radiology (S.K.), Massachusetts General Hospital and Harvard Medical School, Charlestown.

Abstract

BACKGROUND: The current management of patients with stroke with intravenous thrombolysis and endovascular thrombectomy is effective only when it is timely performed on an appropriately selected but minor fraction of patients. The development of novel adjunctive therapy is highly desired to reduce morbidity and mortality with stroke. Since endothelial dysfunction is implicated in the pathogenesis of stroke and is featured with suppressed endothelial nitric oxide synthase (eNOS) with concomitant nitric oxide deficiency, restoring endothelial nitric oxide represents a promising approach to treating stroke injury. METHODS: This is a preclinical proof-of-concept study to determine the therapeutic effect of transcranial treatment with a low-power near-infrared laser in a mouse model of ischemic stroke. The laser treatment was performed before the middle cerebral artery occlusion with a filament. To determine the involvement of eNOS phosphorylation, unphosphorylatable eNOS S1176A knock-in mice were used. Each measurement was analyzed by a 2-way ANOVA to assess the effect of the treatment on cerebral blood flow with laser Doppler flowmetry, eNOS phosphorylation by immunoblot analysis, and stroke outcomes by infarct volumes and neurological deficits. RESULTS: Pretreatment with a 1064-nm laser at an irradiance of 50 mW/cm 2 improved cerebral blood flow, eNOS phosphorylation, and stroke outcomes. CONCLUSIONS: Near-infrared II photobiomodulation could offer a noninvasive and low-risk adjunctive therapy for stroke injury. This new modality using a physical parameter merits further consideration to develop innovative therapies to prevent and treat a wide array of cardiovascular diseases.

Publisher

Ovid Technologies (Wolters Kluwer Health)

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