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Article ; Online: Traumatic Brain Injury Recovery with Photobiomodulation: Cellular Mechanisms, Clinical Evidence, and Future Potential.

Lim, Lew

2024 Volume 13, Issue 5

Abstract: Traumatic Brain Injury (TBI) remains a significant global health challenge, lacking effective pharmacological treatments. This shortcoming is attributed to TBI's heterogeneous and complex pathophysiology, which includes axonal damage, mitochondrial ... ...

Abstract	Traumatic Brain Injury (TBI) remains a significant global health challenge, lacking effective pharmacological treatments. This shortcoming is attributed to TBI's heterogeneous and complex pathophysiology, which includes axonal damage, mitochondrial dysfunction, oxidative stress, and persistent neuroinflammation. The objective of this study is to analyze transcranial photobiomodulation (PBM), which employs specific red to near-infrared light wavelengths to modulate brain functions, as a promising therapy to address TBI's complex pathophysiology in a single intervention. This study reviews the feasibility of this therapy, firstly by synthesizing PBM's cellular mechanisms with each identified TBI's pathophysiological aspect. The outcomes in human clinical studies are then reviewed. The findings support PBM's potential for treating TBI, notwithstanding variations in parameters such as wavelength, power density, dose, light source positioning, and pulse frequencies. Emerging data indicate that each of these parameters plays a role in the outcomes. Additionally, new research into PBM's effects on the electrical properties and polymerization dynamics of neuronal microstructures, like microtubules and tubulins, provides insights for future parameter optimization. In summary, transcranial PBM represents a multifaceted therapeutic intervention for TBI with vast potential which may be fulfilled by optimizing the parameters. Future research should investigate optimizing these parameters, which is possible by incorporating artificial intelligence.
MeSH term(s)	Humans ; Low-Level Light Therapy/methods ; Artificial Intelligence ; Brain Injuries, Traumatic ; Neurons ; Axons
Language	English
Publishing date	2024-02-23
Publishing country	Switzerland
Document type	Journal Article ; Review
ZDB-ID	2661518-6
ISSN	2073-4409 ; 2073-4409
ISSN (online)	2073-4409
ISSN	2073-4409
DOI	10.3390/cells13050385
Database	MEDical Literature Analysis and Retrieval System OnLINE

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Article ; Online: Photobiomodulation effects on cancer cells through modifications of their bioelectric properties: Comment on "The distinguishing electrical properties of cancer cells" by E. di Gregorio, S. Israel, M. Staelens, et al.

Lim, Lew

Physics of life reviews

2023 Volume 46, Page(s) 283–285

Language	English
Publishing date	2023-08-18
Publishing country	Netherlands
Document type	Journal Article
ZDB-ID	2148883-6
ISSN	1873-1457 ; 1571-0645
ISSN (online)	1873-1457
ISSN	1571-0645
DOI	10.1016/j.plrev.2023.08.008
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Article ; Online: Pulsed Near Infrared Transcranial and Intranasal Photobiomodulation Significantly Modulates Neural Oscillations: a pilot exploratory study.

Zomorrodi, Reza / Loheswaran, Genane / Pushparaj, Abhiram / Lim, Lew

Scientific reports

2019 Volume 9, Issue 1, Page(s) 6309

Abstract: Transcranial photobiomodulation (tPBM) is the application of low levels of red or near-infrared (NIR) light to stimulate neural tissues. Here, we administer tPBM in the form of NIR light (810 nm wavelength) pulsed at 40 Hz to the default mode network ( ... ...

Abstract	Transcranial photobiomodulation (tPBM) is the application of low levels of red or near-infrared (NIR) light to stimulate neural tissues. Here, we administer tPBM in the form of NIR light (810 nm wavelength) pulsed at 40 Hz to the default mode network (DMN), and examine its effects on human neural oscillations, in a randomized, sham-controlled, double-blinded trial. Using electroencephalography (EEG), we found that a single session of tPBM significantly increases the power of the higher oscillatory frequencies of alpha, beta and gamma and reduces the power of the slower frequencies of delta and theta in subjects in resting state. Furthermore, the analysis of network properties using inter-regional synchrony via weighted phase lag index (wPLI) and graph theory measures, indicate the effect of tPBM on the integration and segregation of brain networks. These changes were significantly different when compared to sham stimulation. Our preliminary findings demonstrate for the first time that tPBM can be used to non-invasively modulate neural oscillations, and encourage further confirmatory clinical investigations.
MeSH term(s)	Aged ; Brain/physiopathology ; Brain Waves ; Cross-Over Studies ; Double-Blind Method ; Female ; Humans ; Male ; Middle Aged ; Nerve Net
Language	English
Publishing date	2019-04-19
Publishing country	England
Document type	Journal Article ; Randomized Controlled Trial
ZDB-ID	2615211-3
ISSN	2045-2322 ; 2045-2322
ISSN (online)	2045-2322
ISSN	2045-2322
DOI	10.1038/s41598-019-42693-x
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Article: Changes in Brain Function and Structure After Self-Administered Home Photobiomodulation Treatment in a Concussion Case.

Chao, Linda L / Barlow, Cody / Karimpoor, Mahta / Lim, Lew

Frontiers in neurology

2020 Volume 11, Page(s) 952

Abstract: Traumatic brain injury (TBI) is a common neurological disorder among athletes. Although there are no widely accepted treatments for TBI, new investigational approaches, such as photobiomodulation (PBM), are being tested. PBM is a light therapy that uses ... ...

Abstract	Traumatic brain injury (TBI) is a common neurological disorder among athletes. Although there are no widely accepted treatments for TBI, new investigational approaches, such as photobiomodulation (PBM), are being tested. PBM is a light therapy that uses red to near-infrared (NIR) light to stimulate, heal, and protect tissue that has been injured or is at risk of dying. Benefits following transcranial PBM treatments in animal models of acute TBI and a small number of chronic TBI patients have been reported. However, the human PBM TBI studies published to date have been based on behavioral assessments. This report describes changes in behavioral and neuroimaging measures after 8 weeks of PBM treatments. The subject was a 23-year professional hockey player with a history of concussions, presumed to have caused his symptoms of headaches, mild anxiety, and difficulty concentrating. He treated himself at home with commercially available, low-risk PBM devices that used light-emitting diodes (LEDs) to emit 810-nm light pulsing at 10 or 40 Hz delivered by an intranasal and four transcranial modules that targeted nodes of the default mode network (DMN) with a maximum power density of 100 mW/cm
Language	English
Publishing date	2020-09-08
Publishing country	Switzerland
Document type	Case Reports
ZDB-ID	2564214-5
ISSN	1664-2295
ISSN	1664-2295
DOI	10.3389/fneur.2020.00952
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Article ; Online: Near-Infrared Photobiomodulation of Living Cells, Tubulin, and Microtubules

Staelens, Michael / Di Gregorio, Elisabetta / Kalra, Aarat P / Le, Hoa T / Hosseinkhah, Nazanin / Karimpoor, Mahroo / Lim, Lew / Tuszyński, Jack A

Frontiers in medical technology

2022 Volume 4, Page(s) 871196

Abstract: We report the results of experimental investigations involving photobiomodulation (PBM) of living cells, tubulin, and microtubules in buffer solutions exposed to near-infrared (NIR) light emitted from an 810 nm LED with a power density of 25 mW/ ... ...

Abstract	We report the results of experimental investigations involving photobiomodulation (PBM) of living cells, tubulin, and microtubules in buffer solutions exposed to near-infrared (NIR) light emitted from an 810 nm LED with a power density of 25 mW/cm
Language	English
Publishing date	2022-05-04
Publishing country	Switzerland
Document type	Journal Article
ISSN	2673-3129
ISSN (online)	2673-3129
DOI	10.3389/fmedt.2022.871196
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Book ; Online: Raman Spectroscopy Reveals Photobiomodulation-Induced {\alpha}-Helix to {\beta}-Sheet Transition in Tubulins

Di Gregorio, Elisabetta / Staelens, Michael / Hosseinkhah, Nazanin / Karimpoor, Mahroo / Liburd, Janine / Lim, Lew / Shankar, Karthik / Tuszynski, Jack A.

Potential Implications for Alzheimer's and Other Neurodegenerative Diseases

2023

Abstract: In this study, we employed a Raman spectroscopic analysis of the amide I band of polymerized samples of tubulin exposed to pulsed low-intensity NIR radiation (810 nm, 10 Hz, 22.5 J/cm$^{2}$ dose). Peaks in the Raman fingerprint region (300$\unicode{x2013} ...

Abstract	In this study, we employed a Raman spectroscopic analysis of the amide I band of polymerized samples of tubulin exposed to pulsed low-intensity NIR radiation (810 nm, 10 Hz, 22.5 J/cm$^{2}$ dose). Peaks in the Raman fingerprint region (300$\unicode{x2013}$1900 cm$^{-1}$), in particular, in the amide I band (1600$\unicode{x2013}$1700 cm$^{-1}$), can be used to quantify the percentage of protein secondary structures. Under this band, hidden signals of $\mathrm{C}$=$\mathrm{O}$ stretching, belonging to different structures, are superimposed$\unicode{x2014}$producing a complex signal as a result. An accurate decomposition of the amide I band is therefore required for the reliable analysis of the conformation of proteins, which we achieved through a straightforward method employing a Voigt profile. This approach was validated through secondary structure analyses of unexposed control samples, for which comparisons with other values available in the literature could be conducted. Subsequently, using this validated method, we present novel findings of statistically significant alterations in the secondary structures of NIR-exposed tubulin, characterized by a notable decrease in alpha-helix content and a concurrent increase in beta-sheets compared to the control samples. The alpha-helix to beta-sheet transition suggests that PBM reduces microtubule stability and introduces dynamism to allow for the remodeling and, consequently, refreshing of microtubule structures. This newly discovered mechanism could have implications for reducing the risks associated with brain aging, including neurodegenerative diseases like Alzheimer's disease. Comment: 15 pages, 3 figures
Keywords	Quantitative Biology - Biomolecules ; Quantitative Biology - Quantitative Methods
Subject code	500
Publishing date	2023-11-07
Publishing country	us
Document type	Book ; Online
Database	BASE - Bielefeld Academic Search Engine (life sciences selection)

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Article ; Online: Significant Improvement in Cognition in Mild to Moderately Severe Dementia Cases Treated with Transcranial Plus Intranasal Photobiomodulation: Case Series Report.

Saltmarche, Anita E / Naeser, Margaret A / Ho, Kai Fai / Hamblin, Michael R / Lim, Lew

Photomedicine and laser surgery

2017 Volume 35, Issue 8, Page(s) 432–441

Abstract: Objective: This study investigated whether patients with mild to moderately severe dementia or possible Alzheimer's disease (AD) with Mini-Mental State Exam (MMSE) Baseline scores of 10-24 would improve when treated with near-infrared photobiomodulation ...

Abstract	Objective: This study investigated whether patients with mild to moderately severe dementia or possible Alzheimer's disease (AD) with Mini-Mental State Exam (MMSE) Baseline scores of 10-24 would improve when treated with near-infrared photobiomodulation (PBM) therapy. Background: Animal studies have presented the potential of PBM for AD. Dysregulation of the brain's default mode network (DMN) has been associated with AD, presenting the DMN as an identifiable target for PBM. Materials and methods: The study used 810 nm, 10 Hz pulsed, light-emitting diode devices combining transcranial plus intranasal PBM to treat the cortical nodes of the DMN (bilateral mesial prefrontal cortex, precuneus/posterior cingulate cortex, angular gyrus, and hippocampus). Five patients with mild to moderately severe cognitive impairment were entered into 12 weeks of active treatment as well as a follow-up no-treatment, 4-week period. Patients were assessed with the MMSE and Alzheimer's Disease Assessment Scale (ADAS-cog) tests. The protocol involved weekly, in-clinic use of a transcranial-intranasal PBM device; and daily at-home use of an intranasal-only device. Results: There was significant improvement after 12 weeks of PBM (MMSE, p < 0.003; ADAS-cog, p < 0.023). Increased function, better sleep, fewer angry outbursts, less anxiety, and wandering were reported post-PBM. There were no negative side effects. Precipitous declines were observed during the follow-up no-treatment, 4-week period. This is the first completed PBM case series to report significant, cognitive improvement in mild to moderately severe dementia and possible AD cases. Conclusions: Results suggest that larger, controlled studies are warranted. PBM shows potential for home treatment of patients with dementia and AD.
MeSH term(s)	Aged ; Aged, 80 and over ; Alzheimer Disease/diagnosis ; Alzheimer Disease/radiotherapy ; Female ; Humans ; Low-Level Light Therapy/methods ; Male ; Neuropsychological Tests ; Prognosis ; Risk Assessment ; Sampling Studies ; Severity of Illness Index ; Treatment Outcome
Language	English
Publishing date	2017-02-10
Publishing country	United States
Document type	Journal Article
ZDB-ID	2158446-1
ISSN	1557-8550 ; 1549-5418
ISSN (online)	1557-8550
ISSN	1549-5418
DOI	10.1089/pho.2016.4227
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Article ; Online: Home-use Photobiomodulation Device Treatment Outcomes for COVID-19

medRxiv

Abstract: BACKGROUND There is need for non-pharmaceutical treatments for COVID-19. A home-use photobiomodulation (PBM) device was tested as Treatment in a randomized clinical trial. METHODS 294 patients were randomized with equal allocation to Treatment or ... ...

Abstract	BACKGROUND There is need for non-pharmaceutical treatments for COVID-19. A home-use photobiomodulation (PBM) device was tested as Treatment in a randomized clinical trial. METHODS 294 patients were randomized with equal allocation to Treatment or Standard of Care (Control). 199 qualified for efficacy analyses. The Treatment group self-treated for 20 minutes twice daily, for the first 5 days, and subsequently once daily for 30 days. A validated respiratory questionnaire was used, and patients were monitored remotely. The primary endpoint was the time-to-recovery (3 consecutive days of no sickness) for general sickness. The Kaplan-Meier method and the Cox Proportional Hazards model were primary methods of analyses. RESULTS Treatment patients with collective 0-12 days of symptoms, at moderate-to-severe level on Day 1 of Treatment, did not recover significantly faster than Control. However, for patients with 0-7 days of symptoms there was a significant mean difference of 3 days: Treatment, 18 days (95% CI, 13-20) vs. Control, 21 days (95% CI, 15-28), P=0.050. The Treatment:Control hazard ratio at 1.495 (95% CI, 0.996-2.243), P=0.054 exceeded the pre-trial target of 1.44. Treated patients exceeding 7 days symptoms duration were more tired and had lower energy. None of the patients in the Treatment group suffered death or hospitalization while the Control group had 1 death and 3 severe adverse events requiring hospitalization. CONCLUSIONS Patients with up to 7 days of symptoms at moderate-to-severe levels on first day of Treatment can expect faster recovery for general sickness and several respiratory symptoms. (Funded by Vielight Inc.; ClinicalTrials.gov number, NCT04418505.)
Keywords	covid19
Language	English
Publishing date	2022-06-17
Publisher	Cold Spring Harbor Laboratory Press
Document type	Article ; Online
DOI	10.1101/2022.06.16.22276503
Database	COVID19

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Article ; Online: Measures of resting state EEG rhythms for clinical trials in Alzheimer's disease: Recommendations of an expert panel.

Babiloni, Claudio / Arakaki, Xianghong / Azami, Hamed / Bennys, Karim / Blinowska, Katarzyna / Bonanni, Laura / Bujan, Ana / Carrillo, Maria C / Cichocki, Andrzej / de Frutos-Lucas, Jaisalmer / Del Percio, Claudio / Dubois, Bruno / Edelmayer, Rebecca / Egan, Gary / Epelbaum, Stephane / Escudero, Javier / Evans, Alan / Farina, Francesca / Fargo, Keith /

Fernández, Alberto / Ferri, Raffaele / Frisoni, Giovanni / Hampel, Harald / Harrington, Michael G / Jelic, Vesna / Jeong, Jaeseung / Jiang, Yang / Kaminski, Maciej / Kavcic, Voyko / Kilborn, Kerry / Kumar, Sanjeev / Lam, Alice / Lim, Lew / Lizio, Roberta / Lopez, David / Lopez, Susanna / Lucey, Brendan / Maestú, Fernando / McGeown, William J / McKeith, Ian / Moretti, Davide Vito / Nobili, Flavio / Noce, Giuseppe / Olichney, John / Onofrj, Marco / Osorio, Ricardo / Parra-Rodriguez, Mario / Rajji, Tarek / Ritter, Petra / Soricelli, Andrea / Stocchi, Fabrizio / Tarnanas, Ioannis / Taylor, John Paul / Teipel, Stefan / Tucci, Federico / Valdes-Sosa, Mitchell / Valdes-Sosa, Pedro / Weiergräber, Marco / Yener, Gorsev / Guntekin, Bahar

Alzheimer's & dementia : the journal of the Alzheimer's Association

2021 Volume 17, Issue 9, Page(s) 1528–1553

Abstract: The Electrophysiology Professional Interest Area (EPIA) and Global Brain Consortium endorsed recommendations on candidate electroencephalography (EEG) measures for Alzheimer's disease (AD) clinical trials. The Panel reviewed the field literature. As most ...

Abstract	The Electrophysiology Professional Interest Area (EPIA) and Global Brain Consortium endorsed recommendations on candidate electroencephalography (EEG) measures for Alzheimer's disease (AD) clinical trials. The Panel reviewed the field literature. As most consistent findings, AD patients with mild cognitive impairment and dementia showed abnormalities in peak frequency, power, and "interrelatedness" at posterior alpha (8-12 Hz) and widespread delta (< 4 Hz) and theta (4-8 Hz) rhythms in relation to disease progression and interventions. The following consensus statements were subscribed: (1) Standardization of instructions to patients, resting state EEG (rsEEG) recording methods, and selection of artifact-free rsEEG periods are needed; (2) power density and "interrelatedness" rsEEG measures (e.g., directed transfer function, phase lag index, linear lagged connectivity, etc.) at delta, theta, and alpha frequency bands may be use for stratification of AD patients and monitoring of disease progression and intervention; and (3) international multisectoral initiatives are mandatory for regulatory purposes.
MeSH term(s)	Alzheimer Disease/physiopathology ; Brain/physiopathology ; Clinical Trials as Topic ; Cognitive Dysfunction/physiopathology ; Disease Progression ; Electroencephalography/standards ; Humans
Language	English
Publishing date	2021-04-15
Publishing country	United States
Document type	Journal Article ; Review
ZDB-ID	2211627-8
ISSN	1552-5279 ; 1552-5260
ISSN (online)	1552-5279
ISSN	1552-5260
DOI	10.1002/alz.12311
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