John Mitrofanis

University College London | UCL · Institute of Ophthalmology

Autism is a neurodevelopmental condition that starts in childhood and continues into adulthood. The core characteristics include difficulties with social interaction and communication, together with restricted and repetitive behaviours. There are a number of key abnormalities of brain structure and function that trigger these behavioural patterns,...

This systematic review examines the effect of photobiomodulation (PBM), the application of red to near infrared light on body tissues, on the neuroinflammatory response and oxidative stress in animal models of neurodegenerative diseases. The research question and search protocol were prospectively registered on the PROSPERO database. Neurodegenerat...

Although the cause(s) of Alzheimer’s disease in the majority of cases remains elusive, it has long been associated with hypertension. In animal models of the disease, hypertension has been shown to exacerbate Alzheimer-like pathology and behavior, while in humans, hypertension during mid-life increases the risk of developing the disease later in li...

Sleep is a critical part of our daily routine. It impacts every organ and system of our body, from the brain to the heart and from cellular metabolism to immune function. A consistent daily schedule of quality sleep makes a world of difference to our health and well-being. And yet, despite its importance, so many individuals have trouble sleeping w...

Mitochondria are optically responsive organelles producing energy for cell function via adenosine triphosphate (ATP). But ATP production appears to vary over the day. Here we use Drosophila melanogaster to reveal daily shifts in whole animal ATP production in a tight 24h time series. We show a marked production peak in the morning that declines aro...

Over the last seventy years or so, many previous studies have shown that photobiomodulation, the use of red to near infrared light on body tissues, can improve central and peripheral neuronal function and survival in both health and in disease. These improvements are thought to arise principally from an impact of photobiomodulation on mitochondrial...

Epilepsy is synonymous with individuals suffering repeated “fits” or seizures. The seizures are triggered by bursts of abnormal neuronal activity, across either the cerebral cortex and/or the hippocampus. In addition, the seizure sites are characterized by considerable neuronal death. Although the factors that generate this abnormal activity and de...

Objective: To investigate the potential relationship between opsins and photobiomodulation. Background: Opsins and other photoreceptors occur in all phyla and are important in light-activated signaling and organism homeostasis. In addition to the visual opsin systems of the retina (OPN1 and OPN2), there are several non-visual opsins found throughou...

Objective: To assess whether remote application of photobiomodulation (PBM) is effective in reducing clinical signs of Parkinson's disease (PD). Background: PD is a progressive neurodegenerative disease for which there is no cure and few treatment options. There is a strong link between the microbiome-gut-brain axis and PD. PBM in animal models can...

Mitochondria produce energy for cell function via adenosine triphosphate (ATP) and are regulated by a molecular 24h clock. Here we use Drosophila melanogaster to reveal shifts in whole animal ATP production over 24h, showing a marked peak in the morning that declines around midday and remains low from then through to the following morning. Mitochon...

Background: Parkinson's disease (PD) is a progressive neurodegenerative disease with no cure and few treatment options. Its incidence is increasing due to aging populations, longer disease duration and potentially as a COVID-19 sequela. Photobiomodulation (PBM) has been successfully used in animal models to reduce the signs of PD and to protect do...

BACKGROUND: Parkinson's disease (PD) is a progressive neurodegenerative disease with no cure and few treatment options. Its incidence is increasing due to aging populations, longer disease duration and potentially as a COVID-19 sequela. Photobiomodulation (PBM) has been successfully used in animal models to reduce the signs of PD and to protect dop...

In recent times, photobiomodulation has been shown to be beneficial in animal models of Parkinson’s disease, improving locomotive behavior and being neuroprotective. Early observations in people with Parkinson’s disease have been positive also, with improvements in the non-motor symptoms of the disease being evident most consistently. Although the...

Using fMRI (functional magnetic resonance imaging), we explored the effect of transcranial photobiomodulation on four major resting-state brain networks, namely the sensorimotor, salience, default mode and central executive networks, in normal young subjects. We used a vielight transcranial device (810 nm) and compared the scans in 20 subjects (mea...

Previous studies have reported many pharmaceutical and herbal agents, together with some surgical methods, offering neuroprotection in animal models of Parkinson's disease. The translation of these experimental findings to the clinic has been largely disappointing, however. This review focuses on three therapies that are not pharmaceutical, herbal,...

We explore whether near infrared light can change patterns of resting (task-negative) and/or evoked (task-positive; eg finger-tapping) brain activity in normal, young human subjects using fMRI (functional magnetic resonance imaging). To this end, we used a vielight transcranial device (810nm) and compared the scans in subjects after active- and sha...

Mitochondria provide energy for cellular function. We examine daily changing patterns of mitochondrial function and metabolism in Drosophila in vivo in terms of their complex (I-IV) activity, ATP production, glycolysis, and whole fly respiration in the morning, afternoon and night. Complex activity and respiration showed significant and unexpected...

Background: Parkinson's disease is a well-known neurological disorder with distinct motor signs and non-motor symptoms. Objective: We report on six patients with Parkinson's disease that used in-house built photobiomodulation (PBM) helmets. Methods: We used "buckets" lined with light-emitting diodes (LEDs) of wavelengths across the red to near-in...

Transcranial photobiomodulation (PBM), which involves the application of low-intensity red to near-infrared light (600-1100nm) to the head, provides neuroprotection in animal models of various neurodegenerative diseases. However, the absorption of light energy by the human scalp and skull may limit the utility of transcranial PBM in clinical contex...

This review brings together observations on the stress-induced regulation of resilience mechanisms in body tissues. It is argued that the stresses that induce tissue resilience in mammals arise from everyday sources: sunlight, food, lack of food, hypoxia and physical stresses. At low levels, these stresses induce an organised protective response in...

Current treatments for Parkinson’s disease (PD) are primarily symptomatic, leaving a need for treatments that mitigate disease progression. One emerging neuroprotective strategy is remote tissue conditioning, in which mild stress in a peripheral tissue (e.g. a limb) induces protection of life-critical organs such as the brain. We evaluated the pote...

In this study, we examined the cellular distribution of encephalopsin (opsin 3; OPN3) expression in the striatum of non-human primates. In addition, because of our long standing interest in Parkinson’s disease and neuroprotection, we examined whether parkinsonian (MPTP; 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine) insult and/or photobiomodulation...

This study explored the effects of long-term photobiomodulation (PBM) on the glial and neuronal organization in the striatum of aged mice. Mice aged 12 months were pretreated with PBM (670 nm) for 20 minutes per day, commencing at 5 months old and continued for 8 months. We had 2 control groups, young at 3 months and aged at 12 months old; these mi...

Abstract Although there have been many pharmacological agents considered to be neuroprotective therapy in Parkinson’s disease (PD) patients, neurosurgical approaches aimed to neuroprotect or restore the degenerative nigrostriatal system have rarely been the focus of in depth reviews. Here, we explore the neuroprotective strategies involving invasiv...

In this study, we explored the effects of a longer term application, up to 12 weeks, of photobiomodulation in normal, naïve macaque monkeys. Monkeys (n = 5) were implanted intracranially with an optical fibre device delivering photobiomodulation (red light, 670 nm) to a midline midbrain region. Animals were then aldehyde-fixed and their brains were...

Intracranial application of red to infrared light, known also as photobiomodulation (PBM), has been shown to improve locomotor activity and to neuroprotect midbrain dopaminergic cells in rodent and monkey models of Parkinson’s disease. In this study, we explored whether PBM has any influence on the number of tyrosine hydroxylase (TH)+cells and the...

We have long accepted that exercise is ‘good for us’; that − put more rigorously − moderate exercise is associated with not just aerobic fitness but also reduced morbidity and reduced mortality from cardiovascular disease and even malignancies. Caloric restriction (moderate hunger) and our exposure to dietary phytochemicals are also emerging as str...

We have reported previously that intracranial application of near-infrared light (NIr) reduces clinical signs and offers neuroprotection in a subacute MPTP (1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine) monkey model of Parkinson’s disease. In this study, we explored whether NIr reduces the gliosis in this animal model. Sections of midbrain (contain...

We have shown previously that when applied separately, 670 nm and 810 nm near infrared light (NIr) reduces behavioural deficits and offers neuroprotection in a MPTP (1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine) mouse model of Parkinson’s disease. Here, we explored the beneficial outcomes when these NIr wavelengths were applied both together, eithe...

Dietary saffron has shown promise as a neuroprotective intervention in clinical trials of retinal degeneration and dementia and in animal models of multiple CNS disorders, including Parkinson's disease. This therapeutic potential makes it important to define the relationship between dose and protection and the mechanisms involved. To explore these...

We have shown previously that near-infrared light (NIr), when applied at the same time as a parkinsonian insult (e.g. 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine; MPTP), reduces behavioural deficits and offers neuroprotection. Here, we explored whether the timing of NIr intervention-either before, at the same time or after the MPTP insult-was impo...

We have reported previously that intracranial application of near-infrared light (NIr) - when delivered at the lower doses of 25J and 35J - reduces clinical signs and offers neuroprotection in a subacute MPTP (1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine) monkey model of Parkinson's disease. In this study, we explored whether a higher NIr dose (125...

Objective: To examine whether near-infrared light (NIr) treatment reduces clinical signs and/or offers neuroprotection in a subacute MPTP (1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine) monkey model of Parkinson's disease. Methods: We implanted an optical fibre device that delivered NIr (670nm) to the midbrain of macaque monkeys, close to the sub...

Alzheimer's and Parkinson's disease are the two most common neurodegenerative disorders. They develop after a progressive death of many neurons in the brain. Although therapies are available to treat the signs and symptoms of both diseases, the progression of neuronal death remains relentless, and it has proved difficult to slow or stop. Hence, the...

OBJECT The authors of this study used a newly developed intracranial optical fiber device to deliver near-infrared light (NIr) to the midbrain of 6-hydroxydopamine (6-OHDA)-lesioned rats, a model of Parkinson’s disease. The authors explored whether NIr had any impact on apomorphine-induced turning behavior and whether it was neuroprotective. METHO...

Parkinson’s disease (PD) is the second most widespread neurodegenerative disease around the world. It is characterised by the signs of resting tremor, bradykinesia and rigidity. The standard treatments for PD are effective at attenuating the motor signs at least at their onset. However they do not efficiently slow the progression of the PD. In anot...

The incidence of intractable age-related neurodegenerative conditions such as Alzheimer's and Parkinson's diseases and age-related macular degeneration is projected to increase substantially over the coming decades with the ageing of the global population. While the burden of disease associated with other chronic conditions has decreased in recent...

La maladie de Parkinson (MP) est une maladie neurodegenerative chronique affectant le systeme dopaminergique et se traduisant par une perte des neurones dopaminergiques (DA) de la substance noire compacta (SNc) et des faisceaux nigro-stries. Le diagnostic precoce de la MP est difficile car 70 % des neurones dopaminergiques de la substance noire son...

ABSTRACT We have used the MPTP (1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine) mouse model to explore whether (i) the neuroprotective effect of near infrared light (NIr) treatment in the SNc is dose-dependent and (ii) the relationship between tyrosine hydroxylase (TH)+ terminal density and glial cells in the caudate-putamen complex (CPu). Mice recei...

We explored whether 810nm near-infrared light (NIr) offered neuroprotection and/or improvement in locomotor activity in an acute 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine (MPTP)-treated mouse model of Parkinson's disease. Mice received MPTP and 810nm NIr treatments, or not, and were tested for locomotive activity in an open-field test. Thereafte...

This review traces evidence that age-related dementia (Alzheimer's disease) results from the destructive impact of the pulse on cerebral vasculature. Evidence is reviewed that the neuropathology of the dementia is caused by the breakdown of small cerebral vessels (silent microbleeds), that the microbleeds result from pulse-induced damage to the cer...

We have previously shown near infrared light (NIr), directed transcranially, mitigates loss of dopaminergic cells in MPTP (1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine)-treated mice, a model of parkinsonism. These findings complement others suggesting NIr treatment protects against damage from various insults. However one puzzling feature of NIr tr...

Parkinson’s disease is a movement disorder with cardinal signs of resting tremor, akinesia, and rigidity. These manifest after a progressive death of many dopaminergic neurons of the midbrain. Unfortunately, the progression of this neuronal death has proved difficult to slow and impossible to reverse despite an intense search for the specific cause...

Previous work has demonstrated the efficacy of irradiating tissue with red to infrared light in mitigating cerebral pathology and degeneration in animal models of stroke, traumatic brain injury, parkinsonism and Alzheimer's disease (AD). Using mouse models, we explored the neuroprotective effect of near infrared light (NIr) treatment, delivered at...

Object: Previous experimental studies have documented the neuroprotection of damaged or diseased cells after applying, from outside the brain, near-infrared light (NIr) to the brain by using external light-emitting diodes (LEDs) or laser devices. In the present study, the authors describe an effective and reliable surgical method of applying to th...

Background We have shown previously that near-infrared light (NIr) treatment or photobiomodulation neuroprotects dopaminergic cells in substantia nigra pars compacta (SNc) from degeneration induced by 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine (MPTP) in Balb/c albino mice, a well-known model for Parkinson’s disease. The present study explores whe...

Background: There is growing evidence that the spice saffron, which contains powerful anti-oxidants, offers protection against neurodegenerative disorders, including age-related macular degeneration and Alzheimer's disease. Objective: We examined whether saffron pre-treatment protects dopaminergic cells of the substantia nigra pars compacta (SNc...

A puzzling feature of reports of near infrared light (NIr) treatment of soft tissue wounds is the lack of laterality in the tissue response - it is typically bilateral after a unilateral exposure. This has led to the idea that NIr has an ‘indirect’ effect on non-irradiated tissues, mediated by circulating ‘factors’. We have recently reported that N...

We examined whether near-infrared light (NIr) treatment (photobiomodulation) saves dopaminergic amacrine cells of the retina in an acute and a chronic 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine (MPTP) mouse model of Parkinson disease. For the acute model, BALB/c mice had MPTP (100 mg/kg) or saline injections over 30 hours, followed by a six-day-s...

We have shown previously that near-infrared light (NIr) treatment or photobiomodulation neuroprotects dopaminergic cells in substantia nigra pars compacta (SNc) from degeneration induced by 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine (MPTP) in mice. The present study explores whether NIr treatment changes the patterns of Fos expression in the subt...

We have shown previously that photobiomodulation or near-infrared light (NIr) treatment protects dopaminergic cells of the substantia nigra pars compacta (SNc) in an acute MPTP (1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine) model of Parkinson's disease (PD). In this study, we tested the protective and rescue action of NIr treatment in a chronic MPT...

In this anatomical study, we have examined the number of tyrosine hydroxylase (TH) cells in the periaqueductal grey matter (PAG) of 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine (MPTP)-treated monkeys and mice; further, we explored whether kainic acid lesion or deep brain stimulation (DBS) of the subthalamic nucleus (STN) in MPTP-treated monkeys has...

This study explores whether near-infrared (NIr) light treatment neuroprotects dopaminergic cells in the substantia nigra pars compacta (SNc) and the zona incerta-hypothalamus (ZI-Hyp) from degeneration in 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine (MPTP)-treated mice. BALB/c albino mice were divided into four groups: 1) Saline, 2) Saline-NIr, 3)...

High-frequency deep brain stimulation (DBS) of the subthalamic nucleus (STN-HFS) is the preferred surgical treatment for advanced Parkinson's disease. In the 15 years since its introduction into clinical practice, many studies have reported on its benefits, drawbacks, and insufficiencies. Despite limited evidence-based data, STN-HFS has been shown...

The discovery in 1987 of the effects of stimulation at high-frequency able to mimic in a reversible and adjustable manner the effects of local destruction of functional targets has revived the functional neurosurgery of movement disorders, and currently other fields of functional neurosurgery such as psychosurgery. VIM thalamotomy allowed demonstra...