Long course hyperbaric oxygen stimulates neurogenesis and attenuates inflammation after ischemic stroke

Long course hyperbaric oxygen stimulates neurogenesis and attenuates inflammation after ischemic stroke

Several studies have provided evidence with regard to the neuroprotection benefits of hyperbaric oxygen (HBO) therapy in cases of stroke, and HBO also promotes bone marrow stem cells (BMSCs) proliferation and mobilization. This study investigates the influence of HBO therapy on the migration of BMSCs, neurogenesis, gliosis, and inflammation after stroke. Rats that sustained transient middle cerebral artery occlusion (MCAO) were treated with HBO three weeks or two days. The results were examined using a behavior test (modified neurological severity score, mNSS) and immunostaining to evaluate the effects of HBO therapy on migration of BMSCs, neurogenesis, and gliosis, and expression of neurotrophic factors was also evaluated. There was a lower mNSS score in the three-week HBO group when compared with the two-day HBO group. Mobilization of BMSCs to an ischemic area was more improved in long course HBO treatments, suggesting the duration of therapy is crucial for promoting the homing of BMSCs to ischemic brain by HBO therapies. HBO also can stimulate expression of trophic factors and improve neurogenesis and gliosis. These effects may help in neuronal repair after ischemic stroke, and increasing the course of HBO therapy might enhance therapeutic effects on ischemic stroke.

Lee YS, Chio CC, Chang CP, Wang LC, Chiang PM, Niu KC, Tsai KJ. Long course hyperbaric oxygen stimulates neurogenesis and attenuates inflammation after ischemic stroke. Mediators Inflamm. 2013;2013:512978. doi: 10.1155/2013/512978. Epub 2013 Feb 21. PMID: 23533308; PMCID: PMC3595722.

Cystatin C Is a Crucial Endogenous Protective Determinant Against Stroke

Cystatin C Is a Crucial Endogenous Protective Determinant Against Stroke

Endogenous neuroprotection can be induced by ischemic and nonischemic preconditioning. However, not all subjects that undergo preconditioning exhibit similar favorable outcome. This study is to explore the molecules responsible for this phenomenon and find new therapeutic targets for stroke.

Adult male Sprague–Dawley rats were subjected to transient middle cerebral artery occlusion. High-throughput proteomic technique, isobaric tag for relative and absolute quantification, was used to screen differentially expressed proteins in the rats that developed ischemic tolerance from hyperbaric oxygen (HBO) preconditioning. The proteomic results were verified by Western blot and ELISA. Then, short interfering RNA and gene knockout rats were used to further determine the pivotal role of candidate proteins in HBO preconditioning–induced endogenous neuroprotection. Finally, lysosomal permeability was tested to elaborate the mechanism underlying this intrinsic neuroprotective effect.

Nine proteins differentially expressed in the serum of rats, which acquired benefits from HBO preconditioning, were screened and identified. Western blot and ELISA revealed that cystatin C (CysC) and mannose-binding lectin protein C were uniquely changed in rats with smaller infarction after HBO preconditioning and cerebral ischemia. Knockdown and knockout of CysC abolished HBO-induced neuroprotection. Moreover, HBO-induced endogenous CysC elevation preserved lysosomal membrane integrity after stroke in wild-type rats but not in CysC siRNA infusion or CysC−/− rats. Most importantly, exogenous CysC also induced neuroprotection against ischemic/reperfusion injury.

Conclusion. CysC is a crucial determinant contributing to endogenous neuroprotection. It is also a novel candidate for stroke treatment through maintaining lysosomal membrane integrity.

Zongping Fang, MD, PhD, Jiao Deng, MD, PhD, Zhixin Wu, MD, Beibei Dong, MD, Shiquan Wang, MD, Xiaodan Chen, MD, Huang Nie, MD, PhD, Hailong Dong, MD, PhD, and Lize Xiong, MD, PhD, Stroke, Volume 48, Issue 2, February 2017, Pages 436-444. https://doi.org/10.1161/STROKEAHA.116.014975.

Hyperbaric Oxygen Induces Late Neuroplasticity in Post Stroke Patients – Randomized, Prospective Trial

Hyperbaric Oxygen Induces Late Neuroplasticity in Post Stroke Patients – Randomized, Prospective Trial

Recovery after stroke correlates with non-active (stunned) brain regions, which may persist for years. The current study aimed to evaluate whether increasing the level of dissolved oxygen by Hyperbaric Oxygen Therapy (HBOT) could activate neuroplasticity in patients with chronic neurologic deficiencies due to stroke.

A prospective, randomized, controlled trial including 74 patients (15 were excluded). All participants suffered a stroke 6–36 months prior to inclusion and had at least one motor dysfunction. After inclusion, patients were randomly assigned to “treated” or “cross” groups. Brain activity was assessed by SPECT imaging; neurologic functions were evaluated by NIHSS, ADL, and life quality. Patients in the treated group were evaluated twice: at baseline and after 40 HBOT sessions. Patients in the cross group were evaluated three times: at baseline, after a 2-month control period of no treatment, and after subsequent 2-months of 40 HBOT sessions. HBOT protocol: Two months of 40 sessions (5 days/week), 90 minutes each, 100% oxygen at 2 ATA. We found that the neurological functions and life quality of all patients in both groups were significantly improved following the HBOT sessions while no improvement was found during the control period of the patients in the cross group. Results of SPECT imaging were well correlated with clinical improvement. Elevated brain activity was detected mostly in regions of live cells (as confirmed by CT) with low activity (based on SPECT) – regions of noticeable discrepancy between anatomy and physiology.

Conclusions. The results indicate that HBOT can lead to significant neurological improvements in post stroke patients even at chronic late stages. The observed clinical improvements imply that neuroplasticity can still be activated long after damage onset in regions where there is a brain SPECT/CT (anatomy/physiology) mismatch.

Efrati S, Fishlev G, Bechor Y, Volkov O, Bergan J, Kliakhandler K, et al. (2013) Hyperbaric Oxygen Induces Late Neuroplasticity in Post Stroke Patients – Randomized, Prospective Trial. PLoS ONE 8(1): e53716. https://doi.org/10.1371/journal.pone.0053716

Hyperoxia preconditioning: the next frontier in neurology?​

Hyperoxia preconditioning: the next frontier in neurology?

Oxygen is indispensable for all aerobic organisms and has become one of the most widely used therapeutic agents. Currently, oxygen not only is applied in the treatment of diseases, but becomes a modality for the prevention of some diseases. Hyperoxia preconditioning with normobaric or hyperbaric oxygen has been found to be protective in some diseases in several animal models and clinical trials. Currently, investigators pay increasing attention to the application of hyperoxia preconditioning in the prevention of common neurological diseases, and encouraging effectiveness has been achieved. In the present short review, we briefly described the development, application and mechanisms of hyperoxia preconditioning the next frontier in the neurology, and the issues in future application of hyperoxia preconditioning were also proposed.

Shanshan Duan, Guiqiang Shao, Ling Yu, Chuancheng Ren. (2015) Angiogenesis contributes to the neuroprotection induced by hyperbaric oxygen preconditioning against focal cerebral ischemia in rats. International Journal of Neuroscience 125:8, pages 625-634.

Repetitive hyperbaric oxygen treatment increases insulin sensitivity in diabetes patients with acute intracerebral hemorrhage

Repetitive HBOT increases insulin sensitivity in diabetes patients with acute intracerebral hemorrhage

The role of hyperbaric oxygen therapy (HBOT) in the treatment of acute ischemic stroke is controversial. This study aims to investigate whether the peripheral insulin sensitivity of type 2 diabetes patients suffering from intracerebral hemorrhage can be increased after HBOT.

Fifty-two type 2 diabetes participants were recruited after being diagnosed with intracerebral hemorrhage in our hospital. Insulin sensitivity was measured by the glucose infusion rate during a hyperinsulinemic euglycemic clamp (80 mU m-2 min-1) at baseline and 10 and 30 days after HBOT sessions. Serum insulin, fasting glucose, and hemoglobin A1C were measured in fasting serum at baseline and after HBOT sessions. In addition, early (∼10 days after onset) and late (1 month after onset) outcomes (National Institutes of Health Stroke Scale, NIHSS scores) and efficacy (changes of NIHSS scores) of HBOT were evaluated.

In response to HBOT, the glucose infusion rate was increased by 37.8%±5.76% at 1 month after onset compared with baseline. Reduced serum insulin, fasting glucose, and hemoglobin A1C were observed after HBOT. Both early and late outcomes of the HBOT group were improved compared with baseline (P<0.001). In the control group, there was significant difference only in the late outcome (P<0.05). In the assessment of efficacy, there were statistically significant differences between the groups when comparing changes in NIHSS scores at 10 days and 1 month after onset (P<0.05).

Conclusion. Peripheral insulin sensitivity was increased following HBOT in type 2 diabetes patients with intracerebral hemorrhage. The HBOT used in this study may be effective for diabetes patients with acute stroke and is a safe and harmless adjunctive treatment.

Xu Q, Wei YT, Fan SB, Wang L, Zhou XP. Repetitive hyperbaric oxygen treatment increases insulin sensitivity in diabetes patients with acute intracerebral hemorrhage. Neuropsychiatr Dis Treat. 2017 Feb 10;13:421-426. doi: 10.2147/NDT.S126288. PMID: 28228657; PMCID: PMC5312693.

Mechanisms and therapeutic effectiveness of pulsed electromagnetic field therapy in oncology

Mechanisms and therapeutic effectiveness of pulsed electromagnetic field therapy in oncology

Cancer is one of the most common causes of death worldwide. Available treatments are associated with numerous side effects and only a low percentage of patients achieve complete remission. Therefore, there is a strong need for new therapeutic strategies. In this regard, Mechanisms and therapeutic effectiveness pulsed electromagnetic field (PEMF) therapy presents several potential advantages including non-invasiveness, safety, lack of toxicity for non-cancerous cells, and the possibility of being combined with other available therapies. Indeed, PEMF stimulation has already been used in the context of various cancer types including skin, breast, prostate, hepatocellular, lung, ovarian, pancreatic, bladder, thyroid, and colon cancer in vitro and in vivo. At present, only limited application of PEMF in cancer has been documented in humans. The referenced article reviews the experimental and clinical evidence of PEMF therapy discussing future perspectives in its use in oncology.

In conclusion, only two clinical studies have used PEMF therapy for cancer treatment. These studies show that PEMF therapy is safe and promising compared to other available cancer therapies. In the future, PEMFs could be used not only as primary therapy but also in combination with other common antineoplastic therapies.
Given that new portable and affordable PEMF devices are increasingly available on the market, future controlled clinical studies are expected to further determine the
potential of PEMF therapy in oncology.

Maria Vadalà, Julio Cesar Morales-Medina, Annamaria Vallelunga, Beniamino Palmieri, Carmen Laurino & Tommaso Iannitti, Cancer Medicine 2016; 5(11):3128–3139 doi: 10.1002/cam4.861


Optimization of a therapeutic electromagnetic field (EMF) to retard breast cancer tumor growth and vascularity

Optimization of a therapeutic electromagnetic field (EMF) to retard breast cancer tumor growth and vascularity

This study provided additional data on the effects of a therapeutic electromagnetic field (EMF) device on growth and vascularization of murine 16/C mammary adenocarcinoma cells implanted in C3H/HeJ mice. Optimization of a Therapeutic EMF treatment significantly suppressed tumor growth in all 7 EMF treated groups. Exposure to 20mT for 10 minutes twice a day was the most effective retard breast cancer tumor growth suppressor vascularity. The effect of EMF treatment on extent of tumor vascularization, necrosis and viable area was determined after euthanasia. The EMF reduced the vascular (CD31 immunohistochemically positive) volume fraction and increased the necrotic volume of the tumor. Treatment with 15 mT for 10 min/d gave the maximum anti-angiogenic effect. Lack of a significant correlation between tumor CD 31 positive area and tumor growth rate indicates a mechanism for suppression of tumor growth in addition to suppression of tumor vascularization.

Conclusion. It is proposed that EMF therapy aimed at suppression of tumor growth and vascularization may prove a safe alternative for patients whether they are or are not candidates for conventional cancer therapy.

Ivan L Cameron, Marko S Markov, W Elaine Hardman Cancer Cell Int. 2014; 14: 125. Published online 2014 Dec 7. doi: 10.1186/s12935-014-0125-5 PMCID: PMC4272545


PEMF Therapy Accelerates Wound Healing in Numerous Studies

PEMF Therapy Accelerates Wound Healing in Numerous Studies

PEMF therapy can be instrumental in the healing of chronic wounds. There are far less studies on the use of PEMF therapy for the benefit of wound healing than there are for other types of injury. However, the evidence is clear that PEMF therapy has a tremendous impact on the process by which this healing occurs. PEMF therapy accelerates wound healing because it has been shown to stimulate the regeneration of nerves and tissues. The FDA approved the use of PEMF therapy for the healing of delayed and non-union fractures, but at this time the FDA has still not given the approval to use this as a prescribed treatment for wound healing IN Numerous.

There are many types of wounds that may benefit from this therapy including:

  • acute wounds
  • bed sores
  • diabetic ulcers
  • post-operative wounds
  • pressure wounds
  • vascular ulcers


PEMF Therapy Aids in Stroke Recovery

PEMF Therapy Aids in Stroke Recovery

A stroke occurs when the blood supply to part of the brain is reduced, depriving brain tissue of oxygen and nutrients. Within minutes, brain damage can occur. After a stroke, many experience partial or complete paralysis of one side of the body. Some experience partial numbness in the fingers and face. More extreme cases of brain damage may experience loss of the ability to walk, talk and function independently. Is there a more effective way to aid in stroke recovery?

The health community often ponders the most effective way to offer rehabilitation after a stroke. Conventional treatment methods take time and can be slow and painstaking. There remains a wonder over whether or not a better treatment option exists. Most commonly, doctors prescribe a combination of medication and physical therapy following a stroke. While these conventional methods are necessary, researchers believe that PEMF therapy can enhance efficacy and accelerate recovery time.

PEMF therapy Aids can assist those recovering from a stroke in a number of ways. By improving energy and circulation, PEMF therapy allows for a more active role in rehabilitation. However, the most substantial way PEMF therapy assists with stroke recovery is by improving the function of nerve cells. When nerve cells misfire, motor control issues arise. This is the brain’s way of telling the body that there is injury or damage present.

On its own, PEMF therapy will not bring full recovery. However, PEMF can aid in acceleration of stroke recovery when used in combination with conventional medical treatments. In a study pertaining to the combined efficacy of PEMF therapy with Physical Therapy (PT), participants received 1 Hz of PEMF over the healthy side of the brain 10 times daily. The researchers found that administering PEMF prior to daily PT allowed for re-balancing of motor excitability. Essentially, the damaged part of the brain was more likely to react well to physical therapy when primed with PEMF therapy prior to the PT session.

Read more

PEMF Therapy Education, Jul 25, 2019.

Pulsed electromagnetic field and relief of hypoxia‐induced neuronal cell death

Pulsed electromagnetic field and relief of hypoxia‐induced neuronal cell death: The signaling pathway

Low‐energy low‐frequency pulsed electromagnetic fields (PEMFs) exert several protective effects, such as the regulation of kinases, transcription factors as well as cell viability in both central and peripheral biological systems. However, it is not clear on which bases they affect neuroprotection and the mechanism responsible is yet unknown.

In this study, we have characterized in nerve growth factor‐differentiated pheochromocytoma PC12 cells injured with hypoxia: (i) the effects of PEMF exposure on cell vitality; (ii) the protective pathways activated by PEMFs to relief neuronal cell death, including adenylyl cyclase, phospholipase C, protein kinase C epsilon and delta, p38, ERK1/2, JNK1/2 mitogen‐activated protein kinases, Akt and caspase‐3; (iii) the regulation by PEMFs of prosurvival heat‐shock proteins of 70 (HSP70), cAMP response element‐binding protein (CREB), brain‐derived neurotrophic factor (BDNF), and Bcl‐2 family proteins. The results obtained in this study show a protective effect of PEMFs that are able to reduce neuronal cell death induced by hypoxia by modulating p38, HSP70, CREB, BDNF, and Bcl‐2 family proteins. Specifically, we found a rapid activation (30 min) of p38 kinase cascade, which in turns enrolles HSP70 survival chaperone molecule, resulting in a significant CREB phosphorylation increase (24 hr). In this cascade, later (48 hr), BDNF and the antiapoptotic signaling pathway regulated by the Bcl‐2 family of proteins are recruited by PEMFs to enhance neuronal survival.

This study paves the way to elucidate the mechanisms triggered by PEMFs to act as a new neuroprotective approach to treat cerebral ischemia by reducing neuronal cell death.

Stefania Gessi, Stefania Merighi, Serena Bencivenni, Enrica Battistello, Fabrizio Vincenzi, Stefania Setti, Matteo Cadossi, Pier Andrea Borea, Ruggero Cadossi, Katia Varani. Journal of Cellular Physiology, January 17, 2019, https://doi.org/10.1002/jcp.28149.