Effect of inhaled xenon on cerebral white matter damage in comatose survivors of out-of-hospital cardiac arrest: a randomized clinical trial. 2023 BioMed Central Ltd unless otherwise stated. The experimental unit (n) in all outcomes represents an animal. 5b(ii)) and bilaterally in the retrosplenial cortex (Fig. CAS Experiments complied with the UK Animals Scientific Procedures Act (1986) and were approved by the Animal Welfare and Ethical Review Body of Imperial College London. However, elderly patients are more likely to have age-related liver, kidney, or heart problems, which may require caution and an adjustment in the dose for patients receiving Xenon Xe 133 gas. Medical-grade xenon usually costs around $10-$20 per 1 kg. In the cortical areas (Fig. Phone: (480) 515-6296. 2018;35(8):103744. 7 Preclinical data have suggested that nintedanib inhibits processes involved in the progression of lung fibrosis. Note: This document contains side effect information about xenon xe-133. WebZACHARY, LOUISIANA: A Black man from Zachary died from multiple gunshot wounds after reportedly confronting his teenage daughter's boyfriend. 2006;37(2):5016. Our aim was to evaluate the potential of xenon as a neuroprotectant for treatment of TBI in a rat model of severe TBI. Animal models of traumatic brain injury and assessment of injury severity. A lawsuit is filed against a hospital recognized as No. WebPatients with disturbed liver function and/or renal function may also benefit because of low toxicity and a lack of hemodynamic depression leading to preserved organ perfusion. 2013;98(5):F437-439. Many of the long-term impairments in locomotor function and cognition that affect TBI survivors result from the potentially preventable secondary injury [26, 40]. As of 2021, xenon is legal in every country.In Europe, there are xenon clinics where you can legally undergo xenon therapy. b Quantification of GFAP-positive area in sham (white bars), TBI control (blue bars) and TBI xenon (red bars) in i motor/medial parietal association cortex (M1/MPtA) & contusional cortex, ii somatosensory cortex (S1BF), iii retrosplenial cortex (RSC) iv hypothalamus, v amygdala, vi hippocampal CA1, vii CA2, viii CA3, ix dentate gyrus (DG) and x corpus callosum. The scale bar is 50m and applies to all images. Article 7b(ii)), the right retrosplenial cortex (Fig. Preservation of somatosensory neurons in the xenon-treated groups may also play a role in the observed improved locomotor function in this group as there is evidence that somatosensory S1 neurons can initiate motor function independent of M1 [44]. Inhaled xenon Xe 129 Hyperpolarized is a magnetic resonance imaging (MRI) contrast agent used to help create a clear picture of the body during an MRI scan. 2009;29(4):70714. Applies to xenon xe-133: inhalation gas. Along with its needed effects, xenon xe-133 (the active ingredient contained in Xenon) may cause some unwanted effects. Although not all of these side effects may occur, if they do occur they may need medical attention. 2012;117(1):3847. The right S1BF is a pericontusional region and the increase in active microglia may represent activation due to proximity to necrotic tissue in the contusion or may represent migration of active microglia toward the contusion. In all subcortical areas except the right somatosensory cortex, the median number of low activity resting microglia was greater in the TBI xenon group compared to the TBI control group, but this did not reach significance. except perhaps that I felt little lighter. 2010;112(3):62330. A craniotomy window (~8mm6mm) was created using a saline-cooled high-speed drill, alongthe coronal and lambdoid sutures and laterally as close as possible to the temporalis muscle insertion. * p<0.05, ** p<0.01, compared to sham group as indicated by brackets, Kruskal Wallis test with Benjamini Yekutieli correction. Lab Anim (NY). Three main groups of patients were identified: Group 1 comprised 20 patients (cases 1-20) in whom there was Zoerle T, Carbonara M, Zanier ER, Ortolano F, Bertani G, Magnoni S, Stocchetti N. Rethinking neuroprotection in severe traumatic brain injury: toward bedside neuroprotection. However in this ROI there was a significant (p<0.05) increase in the number of active microglia in the xenon group compared to sham (Fig. Influence of a brief episode of anesthesia during the induction of experimental brain trauma on secondary brain damage and inflammation. Thoresen M, Hobbs CE, Wood T, Chakkarapani E, Dingley J. Cooling combined with immediate or delayed xenon inhalation provides equivalent long-term neuroprotection after neonatal hypoxia-ischemia. Images were analyzed with FIJI (ImageJ) software [34, 35]. facing urgent problems such as climate change of sudden pandemic. Anticonvulsant effect of xenon on neonatal asphyxial seizures. pursuing this carrier in the Czech Republic, on part time basis. the physical, sexual and psychological level, but I also got much better mental PubMed Median neuronal density in the hypothalamus was reduced in the TBI control group compared to the sham group while median neuronal density in the TBI xenon group was similar to the sham. xenon clinic death J Neurosci Res. Anaesthetics, Pain Medicine and Intensive Care Section, Department of Surgery and Cancer, Imperial College London, Sir Ernst Chain Building, South Kensington, London, SW7 2AZ, UK, Rita Campos-Pires,Haldis Onggradito,Eszter Ujvari,Shughoofa Karimi,Flavia Valeo,Jitka Aldhoun&Robert Dickinson, Royal British Legion Centre for Blast Injury Studies, Department of Bioengineering, Imperial College London, Bessemer Building, South Kensington, London, SW7 2AZ, UK, Charing Cross Hospital Intensive Care Unit, Critical Care Directorate, Imperial College Healthcare NHS Trust, London, UK, Department of Life Sciences, Imperial College London, Sir Ernst Chain Building, South Kensington, London, SW7 2AZ, UK, Department of Anaesthetics, Royal Berkshire Hospital NHS Foundation Trust, London Road, Reading, RG1 5AN, UK, You can also search for this author in b Quantification of Iba1-positive cells from sham (white bars), TBI control (blue bars) and TBI xenon (red bars) in i motor/medial parietal association cortex (M1/MPtA) & contusional cortex, ii somatosensory cortex (S1BF), iii retrosplenial cortex (RSC) iv hypothalamus, v amygdala, vi hippocampal CA1, vii CA2, viii CA3, ix dentate gyrus (DG) and x corpus callosum. volume24, Articlenumber:667 (2020) 3b(iv)). What was remarkable is that xenon-treatment following TBI attenuated both the reduction in overall speed and the reduction in stride length in all limbs. We observed a significant reduction in locomotor speed in the TBI control group at 24h following injury, consistent with a severe CCI injury located over the motor cortex. Sports Med. 3b(i)). *p<0.05, ** p<0.01, *** p<0.001compared to sham group, Mann Whitney U test (contusion), one-way (locomotor speed, cadence) or two way (stride length) ANOVA with Sidak correction. 3b(iii)). California Privacy Statement, HAMILTON'S PHARMACOPEIA: Mondays, 10p | Hamilton Many of the persistent impairments and disabilities experienced by TBI survivors are caused by the potentially preventable secondary injury. Interestingly xenon was also effective in preserving neurons in the contralateral hemisphere that are distant from the site of impact. statement and The CCI model is a well-characterized preclinical rodent model of contusional TBI, one of the most common types of TBI in humans. We chose to examine cortical and subcortical brain regions (Fig. Xenon is a pleiotropic drug with actions at a variety of targets implicated in the secondary injury cascade, including NMDA receptors [6,7,8], potassium channels [9, 10], activation of HIF-1 alpha [11], and an increase in erythropoietin levels [12]. An increase in overall number and number of active microglia following TBI has been observed in previous studies [36, 37] and xenon appears to enhance this homeostatic response. At higher doses, you are likely to notice intense psychedelic effects. In order to increase sensitivity and to observe differences in individual animal performance we calculated the change in each parameter () at 24h compared to the same animal at baseline. At 24h the sham group exhibited a small increase in locomotor speed of 4.0 (1.1) m s1 compared to baseline, perhaps indicating a learning effect (Fig. *p<0.05; ** p<0.01; *** p<0.001, compared to sham group or control TBI group as indicated by brackets, Kruskal Wallis test with Benjamini Yekutieli correction. We observed neuronal loss in the TBI control group compared to uninjured sham group that was not present in the TBI xenon group. Sleep-wake disturbances after traumatic brain injury: synthesis of human and animal studies. You can use this space to go into a little more detail about your company. Stride length at 24h was reduced in all limbs in the TBI control group, reaching significance (p<0.05) in the left hind, right front, and right hind limbs (Fig. beginning of my desire to work with body, energy and consciousness. We designed our study to comply with the ARRIVE guidelines. In my leisure I pursue hobbies such as singing, painting, and yoga. The scale bars are 20m (i) and (ii); and 40m (iii). Crit Care Med. In the current study, the objective was to evaluate the effect of xenon treatment following severe TBI in rats, with a focus on acute functional outcome, neuronal preservation, and glial cell responses in specific brain regions associated with the cognitive, locomotor and other functional deficits experienced by TBI patients. The preservation of neurons in clinically relevant brain regions in the xenon-treated group was associated with an early increase in number of Iba1-positive microglia. Secondary injury was calculated by subtracting the primary injury at 15min from the total contusion volume at 24h. c Controlled cortical impact results in locomotor impairment at 24h after injury that is prevented by xenon treatment. Xenon Clinic Lastly, I a Typical immunostaining showing GFAP (red) staining from sham, TBI control and TBI xenon animals in right hippocampal CA1 region. CAS Moderate hypothermia within 6 h of birth plus inhaled xenon versus moderate hypothermia alone after birth asphyxia (TOBY-Xe): a proof-of-concept, open-label, randomised controlled trial. The Gas Safety Trust, London United Kingdom. 2008;36:58895. Yoga practice marks the Trends Pharmacol Sci. In order to avoid any confounding effects from the anesthesia and analgesia, we were careful to ensure that the sham group received exactly the same drugs. Neuronal loss in this region may therefore be unavoidable. a Typical cresyl violet stained slices for i TBI primary injury at 15min, ii TBI control at 24h and iii TBI xenon at 24h. b(i) In animals treated with control gas, the injury develops significantly between 15min (grey bar) and 24h (dark blue hatched bar). Crit Care 24, 667 (2020). Xenon is a trace gas in Earths atmosphere representing no > 0.0875 ppm. The far-reaching scope of neuroinflammation after traumatic brain injury. Abraini JH, David HN, Lemaire M. Potentially neuroprotective and therapeutic properties of nitrous oxide and xenon. Feigin VL, Theadom A, Barker-Collo S, Starkey NJ, McPherson K, Kahan M, Dowell A, Brown P, Parag V, Kydd R, et al. 1e). d Cadence was significantly reduced in both the TBI control group and the TBI xenon group at 24h following injury. Live neurons show a strong NeuN staining combined with DAPI. In a report released Tuesday, the VA Inspector General's office (OIG) found that 215 deceased patients had open specialist consultation appointments at the Phoenix A medium of a great potential. Xenon treatment reduced secondary injury volume by 34%, consistent with the reduction of 38% observed in a mouse model of TBI treated with the higher concentration of 75% xenon [41]. * p<0.05, ** p<0.01, compared to sham group as indicated by brackets, Kruskal Wallis test with Benjamini Yekutieli correction. Hamilton Morris on Twitter Figure5a shows representative Iba1-positive microglia in the left hypothalamus from sham, TBI control and TBI xenon groups. The animals temperature was monitored using a rectal temperature probe before and after administration of gases and was within normal physiological range. 2019;56(8):533245. Our findings at 24h after injury of neuronal preservation associated with an increase in number of microglia and astrocyte activation are consistent with microglia promoting repair and regeneration mediated by neuroprotective reactive astrocytes. Loane DJ, Faden AI. BBC News Common causes of death worldwide, such as heart disease, chronic lung disease and cancer are often treatable. At the end they Nsledujc kategorie mete povolit i zakzat a svj vbr uloit. Terms and Conditions, Due to tissue damage within the contusion and disruption of cortical layers, it was not possible to quantify neurons in the ipsilateral motor/association cortex. 7) the GFAP-positive area was increased in the xenon-treated group. Humanity is The use of animal models is essential in the later stages of preclinical translation, once screening using in vitro models is complete [21, 22]. Google Scholar. Article Traumatic brain injury (TBI) is a leading cause of death and disability globally [1, 2]. Nintedanib in Progressive Fibrosing Interstitial Lung Images of the footprints are recorded by a video camera under the walkway. Thereafter, it is sufficient to come back I was able to sleep 8 hours a day, but I also could The distribution of microglia classified as resting (low activity) or active based on their size and morphology is shown in Fig. Neuroprotection for traumatic brain injury: translational challenges and emerging therapeutic strategies. 2017;7(1):1576. However, elderly patients are more likely to have age-related liver, kidney, or heart problems, which may require caution and an adjustment in the dose for patients receiving Xenon Xe 133 gas. Neuronal preservation was associated with a xenon-induced enhancement of microglial cell numbers and astrocyte activation, consistent with a role for early beneficial neuroinflammation in xenons neuroprotective effect. Ann N Y Acad Sci. Three consecutive trials were performed for each animal. To quantify reactive astrogliosis, we measured the area of GFAP positive staining within the regions of interest; the GFAP images were binarized after thresholding and the percentage of GFAP stained area within the regions of interest was measured. Single severe traumatic brain injury produces progressive pathology with ongoing contralateral white matter damage one year after injury. I started sleeping better as I 6b. Xenon Xe 133 (Inhalation Route) Proper Use Xenon treatment after severe traumatic brain injury improves locomotor outcome, reduces acute neuronal loss and enhances early beneficial neuroinflammation: a randomized, blinded, controlled animal study, $$\frac{d}{2}*\left({A}_{1 \, }+{A}_{n}\right)+d*\left({A}_{2 \, }+{A}_{3}+\dots +{A}_{n-1}\right)$$, https://doi.org/10.1186/s13054-020-03373-9, http://creativecommons.org/licenses/by/4.0/, http://creativecommons.org/publicdomain/zero/1.0/. 6b(iv)). Maas AIR, Menon DK, Adelson PD, Andelic N, Bell MJ, Belli A, Bragge P, Brazinova A, Buki A, Chesnut RM, et al. 6 and 7 in ( A ). The antibodies and dilutions used were: NeuN (1:200 mouse, clone A60 AlexFuor555 conjugate, MAB 377A5, Merck-Millipore, Watford, Herts, UK); Iba1 (primary: 1:200 rabbit anti-rat, C292720 Lifespan Biosciences, Inc, Seattle, USA; secondary: 1:500 AlexaFluor488 goat anti-rabbit, A11008, Life Technologies, Paisley, UK); GFAP (primary: 1:1000 chicken, AB4674, Abcam Ltd, Cambridge, UK; secondary: 1:200 goat anti-chicken, AlexaFluor647, AB150175, Abcam Ltd, Cambridge, UK). The impactor tip was flat, with a diameter of 4mm, impact velocity of 6ms1, impact duration of 400ms, and penetration depth of 3.0mm. The area of the contusion was measured using image-analysis software (Scopephoto 3.1, Scopetek Opto-Eletric Co., Hangzhou, China) by an investigator blinded to the experimental groups. 21 Those with congestive heart failure may also fare better because of Scientific reports. Sheng SP, Lei B, James ML, Lascola CD, Venkatraman TN, Jung JY, Maze M, Franks NP, Pearlstein RD, Sheng H, et al. In all hippocampal subregions except CA3, there was an increase in the median number of microglia in TBI control group compared to the sham group, but this only reached significance (p<0.01) in the right CA3.