Translational Failure of Photobiomodulation in Ischemic Stroke: A Systematic Review of Oxidative Stress and Dosimetric Limitations

Anang Maulana Yusuf; Prananda Surya Airlangga; Hamzah Hamzah

doi:10.37212/jcnos.1946738

Translational Failure of Photobiomodulation in Ischemic Stroke: A Systematic Review of Oxidative Stress and Dosimetric Limitations

Abstract

Photobiomodulation (PBM) has demonstrated substantial neuroprotective potential in experimental models of ischemic stroke; however, clinical trials have not demonstrated consistent therapeutic efficacy, raising concerns regarding its clinical translation. This review critically evaluates the discrepancy between predominantly favorable preclinical findings and inconclusive clinical outcomes, with particular emphasis on oxidative stress modulation, mitochondrial bioenergetics, neuroinflammation, neurovascular regulation, and dosimetric limitations. A structured literature search was conducted for studies published up to March 2026. Most experimental studies demonstrated that PBM improves neurological recovery, reduces infarct volume, enhances mitochondrial function, restores redox balance, modulates inflammatory signaling pathways, and promotes neurovascular responses following ischemic injury. Several studies also reported improved endothelial nitric oxide synthase activation, enhanced cerebral perfusion, and facilitation of neuronal repair processes. Although most preclinical studies reported favorable outcomes, some investigations demonstrated limited or non significant effects, highlighting heterogeneity within the available experimental evidence. Despite these promising mechanistic effects, translation into human stroke therapy remains limited. Emerging evidence suggests that insufficient intracranial photon penetration caused by attenuation through the scalp, skull, and cerebrospinal tissues may result in subtherapeutic fluence at target brain regions, representing a major barrier to clinical efficacy. This review highlights that the translational limitations of PBM are more likely attributable to inadequate intracranial light delivery and dosimetric mismatch rather than absence of biological activity. PBM remains a promising but investigational adjunctive neuroprotective strategy for ischemic stroke, warranting further optimization of light delivery systems and treatment protocols before widespread clinical application.

Keywords

Supporting Institution

Department of Anesthesiology and Reanimation, Faculty of Medicine, Universitas Airlangga, provided academic and infrastructural support for this work

Ethical Statement

This study is a review of previously published literature and did not involve human participants or animals. Therefore, ethical approval was not required. All data were obtained from publicly available sources, and all original studies were appropriately cited in accordance with research integrity standards.

Thanks

The authors thank the Department of Anesthesiology and Reanimation, Faculty of Medicine, Universitas Airlangga for academic support. The authors confirm that no AI tools or automated programs were used in its preparation.

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Details

Primary Language

English

Subjects

Cellular Nervous System

Journal Section

Review

Authors

Anang Maulana Yusuf ^*
0009-0003-4739-5636
Indonesia

Prananda Surya Airlangga
0000-0002-4674-6751
Indonesia

Hamzah Hamzah
0000-0002-5665-3567
Indonesia

Publication Date

August 20, 2026

Submission Date

May 7, 2026

Acceptance Date

June 15, 2026

Published in Issue

Year 2026 Volume: 18 Number: 2

DOI

https://doi.org/10.37212/jcnos.1946738

IZ

https://izlik.org/JA83NG95RS

Cite

RIS / Bibtex

APA

Yusuf, A. M., Airlangga, P. S., & Hamzah, H. (2026). Translational Failure of Photobiomodulation in Ischemic Stroke: A Systematic Review of Oxidative Stress and Dosimetric Limitations. Journal of Cellular Neuroscience and Oxidative Stress, 18(2), 1315-1327. https://doi.org/10.37212/jcnos.1946738

AMA

1.Yusuf AM, Airlangga PS, Hamzah H. Translational Failure of Photobiomodulation in Ischemic Stroke: A Systematic Review of Oxidative Stress and Dosimetric Limitations. J Cell Neurosci Oxid Stress. 2026;18(2):1315-1327. doi:10.37212/jcnos.1946738

Chicago

Yusuf, Anang Maulana, Prananda Surya Airlangga, and Hamzah Hamzah. 2026. “Translational Failure of Photobiomodulation in Ischemic Stroke: A Systematic Review of Oxidative Stress and Dosimetric Limitations”. Journal of Cellular Neuroscience and Oxidative Stress 18 (2): 1315-27. https://doi.org/10.37212/jcnos.1946738.

EndNote

Yusuf AM, Airlangga PS, Hamzah H (August 1, 2026) Translational Failure of Photobiomodulation in Ischemic Stroke: A Systematic Review of Oxidative Stress and Dosimetric Limitations. Journal of Cellular Neuroscience and Oxidative Stress 18 2 1315–1327.

IEEE

[1]A. M. Yusuf, P. S. Airlangga, and H. Hamzah, “Translational Failure of Photobiomodulation in Ischemic Stroke: A Systematic Review of Oxidative Stress and Dosimetric Limitations”, J Cell Neurosci Oxid Stress, vol. 18, no. 2, pp. 1315–1327, Aug. 2026, doi: 10.37212/jcnos.1946738.

ISNAD

Yusuf, Anang Maulana - Airlangga, Prananda Surya - Hamzah, Hamzah. “Translational Failure of Photobiomodulation in Ischemic Stroke: A Systematic Review of Oxidative Stress and Dosimetric Limitations”. Journal of Cellular Neuroscience and Oxidative Stress 18/2 (August 1, 2026): 1315-1327. https://doi.org/10.37212/jcnos.1946738.

JAMA

1.Yusuf AM, Airlangga PS, Hamzah H. Translational Failure of Photobiomodulation in Ischemic Stroke: A Systematic Review of Oxidative Stress and Dosimetric Limitations. J Cell Neurosci Oxid Stress. 2026;18:1315–1327.

MLA

Yusuf, Anang Maulana, et al. “Translational Failure of Photobiomodulation in Ischemic Stroke: A Systematic Review of Oxidative Stress and Dosimetric Limitations”. Journal of Cellular Neuroscience and Oxidative Stress, vol. 18, no. 2, Aug. 2026, pp. 1315-27, doi:10.37212/jcnos.1946738.

Vancouver

1.Anang Maulana Yusuf, Prananda Surya Airlangga, Hamzah Hamzah. Translational Failure of Photobiomodulation in Ischemic Stroke: A Systematic Review of Oxidative Stress and Dosimetric Limitations. J Cell Neurosci Oxid Stress. 2026 Aug. 1;18(2):1315-27. doi:10.37212/jcnos.1946738