Molecular hydrogen (H₂ ) medicine research has flourished since a landmark publication in Nature Medicine that revealed the antioxidant and cytoprotective effects of hydrogen gas in a focal stroke model. Emerging evidence has consistently demonstrated that molecular hydrogen is a promising therapeutic option for a variety of diseases and the underlying comprehensive mechanisms is beyond pure hydroxyl radicals scavenging. The non-toxicity at high concentrations and rapid cellular diffusion features of molecular hydrogen ensure the feasibility and readiness of its clinical translation to human patients.

[ABSTRACT]  [FULL TEXT]  [PDF]  [Mobile Full text]  [EPub] [CITATIONS]  [PubMed]

Cerebral ischemic stroke is a leading cause of serious long-term disability and cognitive dysfunction. The high mortality and disability of cerebral ischemic stroke is urging the health providers, including anesthesiologists and other perioperative professioners, to seek effective protective strategies, which are extremely limited, especially for those perioperative patients. Intriguingly, several commonly used inhalational anesthetics are recently suggested to possess neuroprotective effects against cerebral ischemia. This review introduces multiple paradigms of inhalational anesthetic treatments that have been investigated in the setting of cerebral ischemia, such as preconditioning, proconditioning and postconditioning with a variety of inhalational anesthetics. The pleiotropic mechanisms underlying these inhalational anesthetics-afforded neuroprotection against stroke are also discussed in detail, including the common pathways shared by most of the inhalational anesthetic paradigms, such as anti-excitotoxicity, anti-apoptosis and anti-inflammation. There are also distinct mechanisms involved in specific paradigms, such as preserving blood brain barrier integrity, regulating cerebral blood flow and catecholamine release. The ready availability of these inhalational anesthetics bedside and renders them a potentially translatable stroke therapy attracting great efforts for understanding of the underlying mechanisms.

[ABSTRACT]  [FULL TEXT]  [PDF]  [Mobile Full text]  [EPub] [CITATIONS]  [PubMed]

Repetitive mild traumatic brain injury (rmTBI) is an important medical concern for adolescent athletes that can lead to long-term disabilities. Multiple mild injuries may exacerbate tissue damage resulting in cumulative brain injury and poor functional recovery. In the present study, we investigated the increased brain vulnerability to rmTBI and the effect of hyperbaric oxygen treatment using a juvenile rat model of rmTBI. Two episodes of mild cortical controlled impact (3 days apart) were induced in juvenile rats. Hyperbaric oxygen (HBO) was applied 1 hour/day × 3 days at 2 atmosphere absolute consecutively, starting at 1 day after initial mild traumatic brain injury (mTBI). Neuropathology was assessed by multi-modal magnetic resonance imaging (MRI) and tissue immunohistochemistry. After repetitive mTBI, there were increases in T2-weighted imaging-defined cortical lesions and susceptibility weighted imaging-defined cortical microhemorrhages, correlated with brain tissue gliosis at the site of impact. HBO treatment significantly decreased the MRI-identified abnormalities and tissue histopathology. Our findings suggest that HBO treatment improves the cumulative tissue damage in juvenile brain following rmTBI. Such therapy regimens could be considered in adolescent athletes at the risk of repeated concussions exposures.

[ABSTRACT]  [FULL TEXT]  [PDF]  [Mobile Full text]  [EPub] [CITATIONS]  [PubMed]

Post-operative cognitive dysfunction (POCD) is associated with morbidity, mortality and increased cost of medical care. However, the neuropathogenesis and targeted interventions of POCD remain largely to be determined. We have found that the peripheral surgical wounding induces an age-dependent Aβ accumulation, neuroinflammation and cognitive impairment in aged mice. Pro-inflammatory cytokine interlukin-6 (IL-6) has been reported to be associated with cognitive impairment in rodents and humans. However, the role of IL-6 in the neuropathogenesis of POCD is unknown. We therefore employed pharmacological (IL-6 antibody) and genetic (knockout of IL-6) approach to investigate whether IL-6 contributed to the peripheral surgical wounding-induced cognitive impairment in aged mice. Abdominal surgery under local anesthesia (peripheral surgical wounding) was established in 18-month-old wild-type and IL-6 knockout mice (n = 6 to 10 in each group). Brain level of IL-6 and cognitive function in the mice were determined by western blot, ELISA at the end of procedure, and Fear Conditioning System at 7 days after the procedure. The peripheral surgical wounding increased the level of IL-6 in the hippocampus of aged wild-type, but not IL-6 knockout mice. IL-6 antibody ameliorated the peripheral surgical wounding-induced cognitive impairment in the aged wild-type mice. Finally, the peripheral surgical wounding did not induce cognitive impairment in the aged IL-6 knockout mice. These data suggested that IL-6 would be a required pro-inflammatory cytokine for the peripheral surgical wounding-induced cognitive impairment. Given this, further studies are warranted to investigate the role of IL-6 in the neuropathogenesis and targeted interventions of POCD.

[ABSTRACT]  [FULL TEXT]  [PDF]  [Mobile Full text]  [EPub] [CITATIONS]  [PubMed]

Acute brain injury is a critical and emergent condition in clinical settings, which needs to be addressed urgently. Commonly acute brain injuries include traumatic brain injury, ischemic and hemorrhagic strokes. Oxidative stress is a key contributor to the subsequent injuries and impedes the reparative process after acute brain injury; therefore, facilitating an anti-oxidative approach is important in the care of those diseases. Readiness to deliver and permeability to blood brain barrier are essential for the use of this purpose. Inhaled anesthetic gases are a group of such agents. In this article, we discuss the anti-oxidative roles of anesthetic gases against acute brain injury.

[ABSTRACT]  [FULL TEXT]  [PDF]  [Mobile Full text]  [EPub] [CITATIONS]  [PubMed]

To date, the therapeutic methods for ischemic and hemorrhagic stroke are still limited. The lack of oxygen supply is critical for brain injury following stroke. Hyperbaric oxygen (HBO), an approach through a process in which patients breathe in 100% pure oxygen at over 101 kPa, has been shown to facilitate oxygen delivery and increase oxygen supply. Hence, HBO possesses the potentials to produce beneficial effects on stroke. Actually, accumulated basic and clinical evidences have demonstrated that HBO therapy and preconditioning could induce neuroprotective functions via different mechanisms. Nevertheless, the lack of clinical translational study limits the application of HBO. More translational studies and clinical trials are needed in the future to develop effective HBO protocols.

[ABSTRACT]  [FULL TEXT]  [PDF]  [Mobile Full text]  [EPub] [CITATIONS]  [PubMed]

The presence of a salvageable penumbra, a region of ischemic brain tissue with sufficient energy for short-term survival, has been widely agreed as the premise for thrombolytic therapy with tissue plasminogen activator (tPA), which remains the only United States Food and Drug Administration (FDA) approved treatment for acute ischemia stroke. However, the use of tPA has been profoundly constrained due to its narrow therapeutic time window and the increased risk of potentially deadly hemorrhagic transformation (HT). Blood brain barrier (BBB) damage within the thrombolytic time window is an indicator for tPA-induced HT and both normobaric hyperoxia (NBO) and hypothermia have been shown to protect the BBB from ischemia/reperfusion injury. Therefore, providing the O₂ as soon as possible (NBO treatment), freezing the brain (hypothermia treatment) to slow down ischemia-induced BBB damage or their combined use may extend the time window for the treatment of tPA. In this review, we summarize the protective effects of NBO, hypothermia or their use combined with tPA on ischemia stroke, based on which, the combination of NBO and hypothermia may be an ideal early stroke treatment to preserve the ischemic penumbra. Given this, there is an urge for large randomized controlled trials to address the effect.

[ABSTRACT]  [FULL TEXT]  [PDF]  [Mobile Full text]  [EPub] [CITATIONS]  [PubMed]

Recent studies suggest that a variety of medical gases confer neuroprotective effects against cerebral ischemia, extending function beyond their regular clinical applications. The mechanisms underlying ischemic neuroprotection afforded by medical gases have been intensively studied over the past two decades. A number of signaling pathways have been proposed, among which anti-inflammatory signaling has been proven to be critical. Pursuit of the role for anti-inflammatory signaling may shed new light on the translational application of medical gas-afforded neuroprotection.

[ABSTRACT]  [FULL TEXT]  [PDF]  [Mobile Full text]  [EPub] [CITATIONS]  [PubMed]

In recent years, hyperbaric oxygen (HBO) has been used in the treatment of a lot of diseases such as decompression sickness, arterial gas embolism, carbon dioxide poisoning, soft tissue infection, refractory osteomyelitis, and problematic wound, but little is known about its application in liver transplantation. Although several studies have been conducted to investigate the protective effects of HBO on liver transplantation and liver preservation, there are still some controversies on this issue, especially its immunomodulatory effect. In this short review, we briefly summarize the findings supporting the application of HBO during liver transplantation (including donors and recipients).

[ABSTRACT]  [FULL TEXT]  [PDF]  [Mobile Full text]  [EPub] [CITATIONS]  [PubMed]

[FULL TEXT]  [PDF] [CITATIONS]  [PubMed]