Engagement of people with multiple sclerosis to enhance research into the physiological effect of hyperbaric oxygen therapy

Abstract

Background: Thousands of people with multiple sclerosis (MS) have used selfadministered oxygen therapy in the UK. Clinical trials have been performed, with scant evidence that people with MS have been consulted to explore how they benefit from or how to optimise this treatment. The conventional MS disease disability scores used in trials seldom reflect the effects individuals report when using oxygen therapy to treat their symptoms.Methods: Three people with MS and the manager of an MS Centre formed a public involvement group and collaborated with clinicians and scientists to inform a lab-based study to investigate the physiological effects of oxygen therapy on microvascular brain endothelial cells.Results: People with MS often use oxygen therapy at a later stage when their symptoms worsen and only after using other treatments. The frequency of oxygen therapy sessions and hyperbaric pressure is individualised and varies for people with MS. Despite direct comparisons of efficacy proving difficult, most individuals are exposed to 100% O2 at 1.5 atmosphere absolute (ATA; 1140 mmHg absolute) for 60 min. In a laboratory-based study human brain endothelial cells were exposed in vitro to 152 mmHg O2 for 60 min with and without pressure, as this equates to 20% O2 achievable via hyperbarics, which was then replicated at atmospheric pressure. A significant reduction in endothelial cells ICAM-1 (CD54) implicated in inflammatory cell margination across the blood brain barrier was observed under oxygen treatment. Conclusions:By collaborating with people living with MS, we were able to design laboratory-based experimental protocols that replicate their treatment regimens to advance our understanding of the physiological effects of hyperbaric oxygen treatment on brain cells and their role in neuroinflammation.

Hyperbaric Oxygen Therapy Alleviates the Autoimmune Encephalomyelitis via the Reduction of IL-17a and GM-Csf Production of Autoreactive T Cells as Well as Boosting the Immunosuppressive IL-10 in the Central Nervous System Tissue Lesions

“…Rationally, we suggested that it is necessary for effective HBOT treatment to manipulate it at an earlier time point nearby disease onset, either before or a little time after onset. Additionally, our evidence partially adds a scientific basis to those studies investigating the protective roles of HBOT in MS patients or neuronal cells [7][8][9]. In 1983, Fischer and colleagues enrolled MS patients for the HBOT treatment trial, and they found a positive initial response for MS patients [7].…”

“…Nevertheless, they still did not prefer to recommend HBOT treatment for MS unless a further confirmation of a long-term follow-up. Recently, HBOT was applied for MS patients and supported a protective role of HBOT in the symptoms of disease [8,9]. The underlying mechanisms were proposed to be related to adhesion molecule ICAM-1 of endothelial cells, maintaining blood brain barrier (BBB) permeability, or the ER stress homeostasis in neuronal cells, eventually, in part, contributing to the protective role of HBOT mentioned as above.…”

“…After the HBOT of one hour, the inner pressure of the chamber was gradually downregulated from 2.5 ATA to normal room oxygen pressure over 20 min. In the vehicle control group, the EAE mice were housed in the cage under the normal room oxygen pressure and moved to the same room of the hyperbaric oxygen chamber [9].…”

“…Of note, Hyperbaric oxygen therapy (HBOT) has been reported to treat some neurological disorders, including experimental spinal cord injury [4], brain injury [5], neurodegenerative disease [6], and MS [7][8][9], already for several decades [9,10]. Moreover, it is increasingly evident that HBOT as an adjunct to therapy strikingly promotes the antiinflammatory responses [11], angiogenesis against hypoxia context [12], and anti-apoptotic capability [13], eventually augmenting the protective roles in neurological disease progression.…”

“…Paradoxically, several clinical trials recommended that HBOT was ineffective for the treatment of MS in previous decades [14][15][16][17][18]. However, there are some reports that HBOT was applied as an adjunct to therapy, and a better remission outcome was observed in MS patients or neuronal cells [7][8][9]. Consequently, the modulatory role of HBOT in MS treatment is still controversial.…”