Xenon Xe 133 (Inhalation Route) Before Using Although we cannot be certain that the improvement in functional deficits at 24h would persist at later times, our previous study in mice demonstrated that early improvement in sensorimotor function was associated with improvements in locomotor speed at 4weeks after injury and in cognitive function 18months after trauma [25, 41]. I work as a Xenon therapist because of my deep wish to help people on their CAS xenon clinic death Traumatic brain injury was performed using a Leica ImpactOne (Leica Biosystems, Milton Keynes, UK) controlled cortical impact device. Xenon (xenon xe-133) is a member of the diagnostic radiopharmaceuticals drug class and is commonly used for Diagnosis and Investigation. The cost for Xenon inhalation gas (10 mCi) is around $327 for a supply of 1 gas, depending on the pharmacy you visit. The area above the dashed-line represents the secondary injury. combining my energy and physical touch or massage. For the neuronal counting in the cortical regions, we used rectangular regions of interest of width 200m spanning cortical layers 1 to 6, a circle of diameter 600m in the amygdala, an oval (520670m) in the hypothalamus; in the hippocampus we used the following rectangular regions of interest: CA1 (30030m), CA2 (20070 m), CA3 (25050 m), DG (two 20050m on top; one 20055m on bottom). Lab Anim (NY). One of the immunohistology slides from the xenon group was damaged and could not be imaged. Campos-Pires R, Hirnet T, Valeo F, Ong BE, Radyushkin K, Aldhoun J, Saville J, Edge CJ, Franks NP, Thal SC, et al. Our CCI impact parameters and the functional and histological outcomes are similar to those classified as a severe injury [28]. 1c). 3b(iv)). Harris K, Armstrong SP, Campos-Pires R, Kiru L, Franks NP, Dickinson R. Neuroprotection against traumatic brain injury by xenon, but not argon, is mediated by inhibition at the N-methyl-D-aspartate receptor glycine site. start with 5 to 10 Xenon therapies. PubMedGoogle Scholar. The images from each trial were processed and analyzed on a computer by Catwalk-XT software and the mean value of the gait parameters obtained. 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. In the left somatosensory cortex, the median value of neuronal density in the TBI control group was less than the sham group but this did not reach significance, while the median value of the xenon-treated group was similar to that of the uninjured sham group ((Fig. Nat Rev Endocrinol. Interestingly the locomotor speed following injury was not significantly different in the xenon-treated TBI group (Fig. Humanity is Scientists used a novel xenon gas scan method to pick up lung abnormalities not identified by routine scans. Mild posttraumatic hypothermia reduces mortality after severe controlled cortical impact in rats. The tip of the controlled cortical impact device was positioned anteriorly above the intact dura~1mm from sagittal suture. Thank you for taking psychedelics responsibly, immature psychonauts are the last thing the psychedelic movement needs.And thank you for being a part of this renaissance. Franks NP, Dickinson R, de Sousa SL, Hall AC, Lieb WR. Normality tests, ANOVA and MannWhitney tests were implemented using GraphPad Prism Version 7.03 software (GraphPad Software Inc., La Jolla, CA). Atlanta, GA: Centers for Disease Control and Prevention, National Center for Injury Prevention and Control; 2010. 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. Williams G, Galna B, Morris ME, Olver J. Spatiotemporal deficits and kinematic classification of gait following a traumatic brain injury: a systematic review. a Typical images showing microglial morphology from sham, TBI control and TBI xenon. Ann N Y Acad Sci. We had six animals in each 24-h group (TBI control; TBI xenon; sham surgery) and four animals in the primary injury group. Similar findings were observed in the amygdala and hypothalamus with significant (p<0.05) increases in the xenon-treated group bilaterally in the hypothalamus and in the left amygdala. Research grade xenon gas is slightly better but both of these contain very few impurities. Primary somatosensory cortex barrel field. Cadence was significantly (p<0.05) reduced in both the TBI control and TBI xenon groups (Fig. Immature people who are not willing to follow the safety guidelines, People who have a familial history of schizophrenia, People who are going through a manic phase of bipolar disorder, If youre going through extremely challenging times, you can take psychedelics but the trips might be unpleasant, By helping each other and educating the public, we psychonauts will soon eliminate the stigma. PubMed 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. We assessed locomotor function at baseline in sham, TBI control and TBI xenon groups before CCI or sham surgery, and again 24h after injury or sham procedure. Isoflurane improves long-term neurologic outcome versus fentanyl after traumatic brain injury in rats. Treatment was started 30min after injury and given for a relatively short duration of 3h in spontaneously breathing animals, modelling a scenario where treatment could be given by first responders and continued in hospital in the neuro-ITU or during neurosurgery. P values of 0.05 or less were taken to indicate a significant difference. NeuN-, Iba1-, and GFAP-positive staining was quantified in the contralateral primary motor/association cortex (M1/MPtA), and bilaterally in the retrosplenial cortex (RSC), barrel field of somatosensory cortex (S1BF), amygdala, ventromedial hypothalamus and hippocampal CA1, CA2, CA3 and DG subregions by observers blinded to the experimental groups. 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. XENON : r/HamiltonMorris - Reddit 2004;75(9):131422. An important caveat is that while the median neuronal cell density in the xenon TBI group were very similar to the sham group and were greater than in the control TBI group, the difference between the TBI groups did not reach significance except in layer 5 of the motor/association cortex. J Neurotrauma. At the individual level, the transformation happens much faster and it is Lastly, I WebThese effects of Xenon have been repeatedly supported by clinical observations of sick and wounded who have been given Xenon anesthesia in Russian hospitals. a Typical immunostaining showing GFAP (red) staining from sham, TBI control and TBI xenon animals in right hippocampal CA1 region. Campos-Pires, R., Onggradito, H., Ujvari, E. et al. https://doi.org/10.1186/s13054-020-03373-9, DOI: https://doi.org/10.1186/s13054-020-03373-9. PubMed Our controlled cortical injury parameters resulted in a primary lesion at 15min of volume 49 (7) mm3, mean (SEM), that developed significantly (p<0.01) increasing to 134 (23) mm at 24h after injury (Fig. Our study was carried out following the ARRIVE guidelines [27] and an important aspect was the randomization of animals to treatment group and that all functional and histological measurements were made by blinded observers. n=4, primary injury 15min (grey bar); n=6 sham (black bars) 24h, n=6, TBI control 24h (blue bars); n=6 TBI xenon 24h (red bars). that in order to tackle these problems on a global scale we need humanity to be healthy, strong and self-confident but also to become mindful, 2009;29(4):70714. Interestingly in the right CA2 there was a small decrease in the median number of microglia in the TBI control and TBI xenon groups compared to sham, that reached significance (p<0.05) in the TBI xenon group. For our study,we chose to combine the widely used inhalational anesthetic isoflurane andthe long-acting opioid buprenorphine both widely used, safe and effective in rodents [32, 33]. BMC Bioinformatics. 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. The scale bars are 20m and applies to all images. In the right S1BF smaller round (resting) microglia predominate in the sham group and TBI control group while in the xenon group there is an increase in number of larger less round and less ramified (active) microglia (Fig. By using this website, you agree to our Figure5 shows quantification of Iba1-positive microglia cortical & subcortical regions. Gas treatments were administered to spontaneously breathing animals in a series of custom-made chambers linked in a closed circuit for a total duration of three hours, starting 30min after CCI injury. 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. Applies to Xenon treatment enhances early microglial proliferation. Our current findings demonstrate for the first time in ratsthat xenon improves functional outcome and prevents neuronal loss. Xenon treatment enhances early astrocyte activation. 6a(i)). Data from this animal are not included in the study and the animal was replaced. Conception and design of study: RD, RCP. Fries M, Nolte KW, Coburn M, Rex S, Timper A, Kottmann K, Siepmann K, Hausler M, Weis J, Rossaint R. Xenon reduces neurohistopathological damage and improves the early neurological deficit after cardiac arrest in pigs. Google Scholar. 2019;123(1):6073. Campos-Pires R, Yonis A, Macdonald W, Harris K, Edge CJ, Mahoney PF, Dickinson R. A novel in vitro model of blast traumatic brain injury. 2017;13(9):572. Traumatic brain injury (TBI) is a major cause of morbidity and mortality, but there are no clinically proven treatments that specifically target neuronal loss and secondary injury development following TBI. Xenon treatment resulted in neuronal preservation in pericontusional areas such as ipsilateral retrosplenial cortex and ipsilateral somatosensory cortex consistent with the reduction in lesion volume. Pediatrics. If we Pischiutta F, Micotti E, Hay JR, Marongiu I, Sammali E, Tolomeo D, Vegliante G, Stocchetti N, Forloni G, De Simoni MG, et al. Following CCI surgery, the craniotomy was closed with the bone flap, sealed with tissue glue (Histoacryl, Braun-Melsungen, Melsungen, Germany) and dental cement (Poly-F Plus, Dentsply Sirona, UK) and the skin sutured. The drugsignificantly inhibits the NMDA receptors. 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. Figure7a shows representative GFAP-positive astrocytes in the right hippocampal CA1 region from sham, TBI control and TBI xenon groups. Controlled cortical impact results in a primary injury that develops significantly 24h later. 1e). The lesion volume of the primary injury group was used to calculate the secondary lesion volume at 24h. Animals were anesthetized with 2.5% isoflurane with buprenorphine analgesia (0.04mgkg1) in an air/oxygen mixture (35% oxygen:65% nitrogen) supplied via a facemask in spontaneously breathing animals. The CatWalk-XT automated gait analysis system (Noldus Information Technology, Wageningen, the Netherlands) was used to measure locomotor function and gait parameters. 2014;133(5):80918. 2017;40:5. The choice of 24h endpoint was determined by our aim of understanding the effects of xenon on neuronal loss and astroglial proliferation at this time point. Arch Dis Child Fetal Neonatal Ed. Gruss M, Bushell TJ, Bright DP, Lieb WR, Mathie A, Franks NP. n=6 sham (white boxes); n=6, TBI control (blue boxes); n=5 TBI xenon (red boxes) * p<0.05, **p<0.01, *** p<0.001, compared to sham group as indicated by brackets, Kruskal Wallis test with Benjamini Yekutieli correction. The median cell density in the xenon-treated groups in these layers was not different to sham. Neurobiology of disease. 3b(i)). tonsillitis inflammations and sore throat at least four times a year, together with For the current study, we used a more severe injury [42] and investigated effects on motor function and specific cell types at an early time-point representative of the time of maximal secondary injury development. Nevertheless in TBI, while it appears that chronic long term microglial activation is harmful, there is evidence that at early time-points microglia are beneficial and assist in clearing debris [50]. 6b. In layer 4 and layer 6 of the left motor cortex a reduction in median neuronal density in the TBI control group was evident compared to sham group but this did not reach significance (Fig. 1c). In a darkened environment (<1lx of illumination), light is reflected downward when the animals paws contact the glass surface. In our current study xenon treatment was given at normothermia. In addition to assessing clinically relevant locomotor outcomes we aimed to do a more complete characterization and determine cellular effects of xenon treatment in brain regions associated with a variety of functional impairments that are common following TBI. We designed our study to comply with the ARRIVE guidelines [27]. Considering the very positive reactions of our clients, I am convinced that Xenon is a very unique medium on our Ma D, Hossain M, Chow A, Arshad M, Battson RM, Sanders RD, Mehmet H, Edwards AD, Franks NP, Maze M. Xenon and hypothermia combine to provide neuroprotection from neonatal asphyxia. PubMed Central Neurons were manually counted using FIJI (ImageJ), in two slices per brain and the mean density calculated. In the contralateral motor cortex we observed a significant reduction neuronal cell density in the TBI control group that was prevented in the xenon-treated group. Abraini JH, David HN, Lemaire M. Potentially neuroprotective and therapeutic properties of nitrous oxide and xenon. Terms and Conditions, We used a quantitative method using the roundness and size of the cell soma in order to classify all the microglia in each ROI as resting or active, with smaller round cells (area<100 m2; roundness>0.5) classified as low activity or resting, and larger irregular cells (area>100 m2; roundness<0.5) classified as active microglia [38]. The reduction in speed was associated with decreased stride length; interestingly the decrease in stride length was present in all limbs and was not lateralized as might be expected from an injury on the right motor cortex. The main downside of xenon is that the gas is expensive and difficult to obtain since there is a finite amount of this element on our planet. Borich MR, Brodie SM, Gray WA, Ionta S, Boyd LA. How long does xenon gas stay in your system? 3b(ii)). We believe The images or other third party material in this article are included in the article's Creative Commons licence, unless indicated otherwise in a credit line to the material. The datasets used and/or analyzed during the current study are available from the corresponding author on reasonable request. We assessed significance of differences in contusion volume using a MannWhitney U test. Loane DJ, Kumar A, Stoica BA, Cabatbat R, Faden AI. A detached retina needs treatment as soon as possible. My decision to work with Xenon was really simple: it significantly helped me, many of my friends and other people around me. In my leisure I pursue hobbies such as singing, painting, and yoga. The duration of the sham surgery and anesthesia was identical to that of the CCI animals. The scale bar is 50m and applies to all images. truly divine power of Xenon and to help them improve their lives and accelerate JAMA. Values are quoted as mean (SEM) for normally distributed data or median (IQR) if data are not normally distributed. At 15min or 24h, animals were terminally anesthetized with pentobarbital and transcardially perfused with 50ml of cold PBS followed by 300ml of cold 4% paraformaldehyde (ThermoFisher Ltd, Hemel Hempstead, Herts, UK). My problems started receding, physical and sexual The contusion is visible in the right hemisphere motor area (left of image). You can understand that after such a transformational experience I simply wanted to bring this opportunity to as many people in need as possible, so for a new position in which I could remain in contact with people on a daily was never really an alcohol drinker, but another side-effect of Xenon is that I prefer to stay almost completely off alcohol. As the null statistics for the KW test are known not to follow a chi-squared distribution for small numbers especially in the region of the 0.95 and 0.99 quantile, results from the KW test were compared to the exact results for a KW test using a program written in Mathematica (Mathematica 11.3.0.0, Wolfram Research Inc.) [39]. Anesthesiology. Because of this, experts believe it is the perfect anesthetic. All 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. 2013;12(1):5364. Coburn M, Maze M, Franks NP. Some of the NeuN-, Iba1- and GFAP-positive distributions in the ROIs were found to be significantly different from a normal distribution and could not be transformed into a normal distribution. Azzopardi D, Robertson NJ, Kapetanakis A, Griffiths J, Rennie JM, Mathieson SR, Edwards AD. 2004;65(2):44352. 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). really turned my life around. Images were captured with a Zeiss AxioObserver inverted widefield microscope (Facility for Imaging by Light Microscopy, Imperial College London) equipped with a motorized stage and a 20objective (Zeiss Plan Apochromat, NA 0.8, WD 0.55mm). The higher dose you take, the more intense these effects will be.With that said, it is impossible to accurately describe the experience through human language.The only way to truly know what xenon feels like is trying xenon.Bad trips rarely happen on this substance. The neuroprotective effect of xenon administration during transient middle cerebral artery occlusion in mice. Google Scholar. Due to tissue damage or imperfections such as folds, it was not possible to make neuronal count measurements in every ROI (eg right RSC, left & right hypothalamus) from every animal (individual points are shown on the graphs). Sections were washed with PBS-0.3% Triton three times, for 20min each, and mounted with Vectashield with DAPI (H1200, Vector Laboratories, Peterborough, UK) and glass coverslips (Menzel-Glser, 2260mm 1 BB022050A1). Stephen Rothery, National Heart and Lung Institute, Imperial College London, for advice on widefield microscopy and image analysis; Zhen Cahilog, Nada Mohamed Ali, Kate Gallagher & Maria Balaet of Department of Surgery & Cancer, Imperial College London for assistance with preliminary histological analysis. Contents: Figure4a shows representative images of NeuN stained neurons in the (i) left hippocampal CA1 region, (ii) left hippocampal dentate gyrus region and (iii) left hypothalamus from sham, TBI control and TBI xenon groups showing neuronal loss in TBI control group that is absent in TBI xenon group. The contusion was evident from a clear difference in the intensity of the cresyl-violet staining. Slices were washed in PBS+0.3% TritonX100) and blocked for 1.5h with 10% normal goat serum (diluted in PBS-0.3% Triton) at room temperature. Will Xenon Be a Stranger or a Friend The Creative Commons Public Domain Dedication waiver (http://creativecommons.org/publicdomain/zero/1.0/) applies to the data made available in this article, unless otherwise stated in a credit line to the data. equipped to deal with the challenges laying ahead. A similar neuroprotective effect of xenon across cortical layers was observed in the pericontusional right somatosensory cortex and right retrosplenial cortex, as well as the corresponding contralateral regions. Interestingly, while xenon treatment was able to prevent neuronal loss in the contralateral hippocampus, in the ipsilateral hippocampus xenon treatment did not preserve neurons. Clinical TBI is associated with impairments in cognitive function, increased anxiety and sleep disturbances; normal functioning of these behaviours is associated with subcortical brain regions. function with less sleep - seven or even six hours a day if needed, without any 4b(ii)). Gas concentrations inside the circuit were monitored continuously via a xenon meter (model 439 EX, Nyquist Ltd, UK) and an oxygen meter (Oxydig, Draeger, Luebeck, Germany) included in the circuit. in my youth in Romania, on professional level. Apr 30, 2023, 12:00 PM. syndrome disappeared. Nevertheless the preservation of neurons in the contralateral hippocampus following xenon treatment is consistent with our previous observation in a mouse model of TBI [41]. The locomotor function data was normally distributed and was analyzed using ANOVA test with Sidak correction.
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