PubMed Central In all other areas there was no significant difference between the control TBI group and the sham group or the xenon treated group. 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. 2018;35(8):103744. Statler KD, Alexander H, Vagni V, Dixon CE, Clark RS, Jenkins L, Kochanek PM. 2016;15(2):14553. Lastly, I except perhaps that I felt little lighter. Sleep-wake disturbances after traumatic brain injury: synthesis of human and animal studies. 1e). CAS 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. We recently demonstrated for the first time in an animal model that xenon is neuroprotective following moderate TBI in mice[25]. Current treatment strategies are largely supportive, and clinically proven neuroprotective treatments are lacking. Cite this article. J Thorac Imaging. Animals were fixed in a stereotactic frame and after being given subcutaneous lidocaine (2mgkg1), a scalp incision was made followed by a craniotomy. beginning of my desire to work with body, energy and consciousness. Maas AIR, Menon DK, Adelson PD, Andelic N, Bell MJ, Belli A, Bragge P, Brazinova A, Buki A, Chesnut RM, et al. 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. d Cadence was significantly reduced in both the TBI control group and the TBI xenon group at 24h following injury. Animal models of traumatic brain injury and assessment of injury severity. 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. ii Treatment with xenon (50%) (red bar) resulted in a 34% reduction in secondary injury compared to untreated control (dark blue bar). Acquisition and analysis of data: RCP, RD, HO, EU, SK, FV, JA, CJE. Interestingly xenon was also effective in preserving neurons in the contralateral hemisphere that are distant from the site of impact. For the quantification of microglia and astrocytes we, used circular regions of interest in the left M1/MPtA (1300m diameter), S1BF (1300m diameter), amygdala (600m diameter), the contusional cortex (700m diameter); oval regions in the RSC (1300600m) and ventromedial hypothalamus (561636m). We feel truly blessed. 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). Manage cookies/Do not sell my data we use in the preference centre. By repeated you in our Xenon clinic! 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. Despite a greater understanding of the pathophysiology of TBI in recent years, current treatment is largely supportive, with no clinically proven treatments specifically targeting neuronal loss and secondary injury development. The CatWalk-XT automated gait analysis system (Noldus Information Technology, Wageningen, the Netherlands) was used to measure locomotor function and gait parameters. In the hippocampus, outlines of total CA1, CA2, CA3 and DG regions were drawn for each slice using the ImageJ line tool; in the corpus callosum, the outline of the central area was drawn for each slice. Emergency Services: YES. I am looking forward to welcoming 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. Conception and design of study: RD, RCP. I heard of 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. At the end they Our aim was to evaluate the efficacy of xenon treatment following severe TBI in rats, with the focus on acute outcomes 24h after trauma. Open Access This article is licensed under a Creative Commons Attribution 4.0 International License, which permits use, sharing, adaptation, distribution and reproduction in any medium or format, as long as you give appropriate credit to the original author(s) and the source, provide a link to the Creative Commons licence, and indicate if changes were made. Understanding the role of the primary somatosensory cortex: opportunities for rehabilitation. The Role of Xenon CT Measurements of Cerebral Blood Flow in 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). 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]. In the cortical areas (Fig. a Typical immunostaining showing GFAP (red) staining from sham, TBI control and TBI xenon animals in right hippocampal CA1 region. Bench-to-bedside review: Molecular pharmacology and clinical use of inert gases in anesthesia and neuroprotection. 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]. The primary injury was in the right motor cortex, and at 24h this area is badly damaged, making accurate neuronal quantification impossible. 3b(iii)). Interestingly, while xenon treatment was able to prevent neuronal loss in the contralateral hippocampus, in the ipsilateral hippocampus xenon treatment did not preserve neurons. I started sleeping better as I Williams G, Galna B, Morris ME, Olver J. Spatiotemporal deficits and kinematic classification of gait following a traumatic brain injury: a systematic review. 2017;7(1):1576. Klose M, Feldt-Rasmussen U. Phone: (480) 515-6296. Locomotor function was assessed using Catwalk-XT automated gait analysis at baseline and 24h after injury. n=6 sham (white boxes) 24h, n=6, TBI control 24h (blue boxes); n=5 TBI xenon 24h (red boxes). 2010;25(5):36674. 5b(vi), (viii), (ix)). 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. Xenon treatment enhances early microglial proliferation. We thank David Macdonald, Phil Rawson, Seth Jetwa, Alex Stepney, Anthony Iglesias & Ray Edgar of Central Biomedical Services, Imperial College London for advice & help with animal husbandry; Phillip Aitken & Laura Abelleira Hervas of Department of Surgery & Cancer, Imperial College London for assistance with perfusions; The Royal Berkshire Hospital, Reading for the kind donation of an Aestiva 5 anaesthetic machine; Ina-Mae Bass for the kind donation of a Hewlett-Packard PC. Therefore, for all the immunohistology the regions of interest in the TBI control, TBI xenon and sham groups were compared using a KruskalWallis (KW) test with Benjamini Yekutieli correction implemented using the statistical program Stata (Version 15, StataCorp, College Station, Texas). function with less sleep - seven or even six hours a day if needed, without any The scale bars are 20m (i) and (ii); and 40m (iii). Xenon Clinic - a new clinic in Prague 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. Quantification of neuronal loss in the left hippocampus showed significant (p<0.05) neuronal loss in the TBI control group in the CA1 and DG sub-regions that was reduced by xenon treatment (Fig. Figure7a shows representative GFAP-positive astrocytes in the right hippocampal CA1 region from sham, TBI control and TBI xenon groups. Scientific reports. 2014;73(1):1429. There was a significant reduction in locomotor speed in the TBI control group at 24h, while this reduction was absent in the TBI xenon group. 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 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. We designed our study to comply with the ARRIVE guidelines. 1d). Taking xenon on a daily or even weekly basis could cause irreversible damage to your brain. In contrast to all other regions, in the contusional cortex, there was a significant (p<0.05) decrease in median number of microglia in both the TBI control group and the xenon-treated group compared to sham, most likely reflecting the gross tissue loss in this region (Figs. We assessed significance of differences in contusion volume using a MannWhitney U test. Xenon is an elemental gas with dissociative, psychoactive, and anesthetic effects. 2018;14(1):5762. The neuroprotective effects of xenon and helium in an in vitro model of traumatic brain injury. In the U.S.A., where I worked as a massage Exp Neurol. b Xenon prevents neuronal loss in specific cortical regions 24h after TBI. Anyone you share the following link with will be able to read this content: Sorry, a shareable link is not currently available for this article. Google Scholar. start with 5 to 10 Xenon therapies. One animal in the xenon group had the treatment start time delayed to 1h in error. 7b(i) (ii), (iii), (iv), (vi), (ix), (x)). Young adult male Sprague Dawley rats n=22, age 13weeks, mean weight (SEM) 429 (7) g at the time of surgery were obtained from Charles River (Margate, Kent, UK). On top of that, a regular drug test would not detect anything. 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. If you vomit while being unconscious, you may die as a consequence. The process of inhaling xenon is virtually the same as the process of inhaling nitrous oxide.However, since xenon is so rare and expensive, it can be difficult to get your hands on it.If you visit a xenon clinic, they will put a mask on you with a mixture of xenon and oxygen and give you the instructions you need.Always sit down before you breathe the gas, or else you might fall. 2) chosen to include both pericontusional areas and areas distant from the lesion core and that are associated with functional impairment observed following TBI. Xenon neuroprotection in experimental stroke: interactions with hypothermia and intracerebral hemorrhage. Animals were group housed (4 per cage) in filter-top cages in a pathogen-free facility in a 12:12 light/dark cycle (7am7pm light) at 22C with ad libitum access to food and water. J Vis Exp. therapist for several years, I discovered and developed the ability to heal by Nature. Competitive inhibition at the glycine site of the N-methyl-D-aspartate receptor by the anesthetics xenon and isoflurane: evidence from molecular modeling and electrophysiology. If material is not included in the article's Creative Commons licence and your intended use is not permitted by statutory regulation or exceeds the permitted use, you will need to obtain permission directly from the copyright holder. Thereafter, it is sufficient to come back 2019;34(2):13650. Neurologic Clin. Dahan A, Yassen A, Bijl H, Romberg R, Sarton E, Teppema L, Olofsen E, Danhof M. Comparison of the respiratory effects of intravenous buprenorphine and fentanyl in humans and rats. 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. i In the left hippocampal CA3, smaller more round (resting) microglia predominate in all groups with increased numbers in xenon-treated group. Progressive neurodegeneration after experimental brain trauma: association with chronic microglial activation. In all of the immunohistological measurements, TBI control and TBI xenon groups were compared with the sham group that had been treated identically to the TBI groups but without impact, in order to ensure that any effects are independent of the drugs administered or surgery. In a darkened environment (<1lx of illumination), light is reflected downward when the animals paws contact the glass surface. New developments in imaging idiopathic pulmonary fibrosis with hyperpolarized Xenon magnetic resonance imaging. a Typical immunostaining showing NeuN (yellow) and DAPI (red) staining from sham, TBI control and TBI xenon animals in i left CA1 hippocampal region, ii left dentate gyrus iii left hypothalamus. Given the dual nature of the inflammatory response, it has been suggested that therapeutic interventions should promote the early helpful inflammation, while preventing the chronic neuroinflammation associated with late-onset cognitive impairment and dementia [50]. Bars are mean values, error bars are SEM. The reason for this is likely explained by the relatively small group sizes, given the variance resulting from the severe injury. Xenon Clinic s.r.o. 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. effect on my work or sport performance that day. BBC News The median values of neuronal cell density in the control TBI group were significantly decreased compared to sham in many brain areas while there was no significant neuronal loss in the xenon treated group in most brain areas. There was a significant (p<0.05) increase in the area of GFAP-positive astrocytes in the xenon-treated group compared to the sham group in the contusional cortex (Fig. A detached retina needs treatment as soon as possible. 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. 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. Franks NP, Dickinson R, de Sousa SL, Hall AC, Lieb WR. He was a great man: dailynews.com Possible PCP lab explosion burns 3 in 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). Brains were carefully removed from the skull and left in 4% paraformaldehyde (in PBS) overnight at 4C, then transferred to 30% sucrose in PBS until the brains sank, before being frozen on powdered dry ice. We classified microglia based on their morphology; resting microglia have smaller rounder soma with high ramification, while activated microglia assume hypertrophic or bushy phenotypes with a larger more amorphous soma with less ramification [36, 37]. Carbon dioxide was removed from the system by soda lime pellets. The lines are medians, boxes represent interquartile interval and whiskers are range. 2012;117(1):3847. Clark RS, Kochanek PM, Marion DW, Schiding JK, White M, Palmer AM, DeKosky ST. 2006;37(2):5016. PubMed Central The cost for Xenon inhalation gas (10 mCi) Pischiutta F, Micotti E, Hay JR, Marongiu I, Sammali E, Tolomeo D, Vegliante G, Stocchetti N, Forloni G, De Simoni MG, et al. There are 2 main types of xenon: medical-grade and research-grade. PubMed Central Crit Care Med. The bone flap was removed exposing the dura above the right parietal cortex, between the sagittal, lambdoid, and coronal sutures. Slices were imaged with a digital camera (Scopetek DCM510, Scopetek Opto-Electric Co., Hangzhou, China) attached to a stereomicroscope (Wild model M8, Heerbrugg, Switzerland). 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]. Values are quoted as mean (SEM) for normally distributed data or median (IQR) if data are not normally distributed. 2000;17(12):117989. Quantification of neuronal cell density of cortical layers from sham (white bars), TBI control (blue bars) and TBI xenon (red bars) in i left hippocampal CA1, CA2, CA3 and DG regions, ii right hippocampal CA1, CA2, CA3 and DG regions, iii left and right amygdala, left and right hypothalamus. Nicholas Franks has disclosed being a named inventor on a number of patents relating to the use of xenon as a neuroprotectant and has a financial interest in the use of xenon as a neuroprotectant. a Typical immunostaining showing Iba1 (green) staining from sham, TBI control and TBI xenon animals in left hypothalamus. Your Xenon Team. 2023 BioMed Central Ltd unless otherwise stated. Two-pore-domain K+ channels are a novel target for the anesthetic gases xenon, nitrous oxide, and cyclopropane. Quantification of neurons (Fig. ( A ) Uptake curves and mean uptake amounts (in liters) of xenon in seven patients (average weight = 72 12 kg) after prior denitrogenation by breathing 100% oxygen for 1520 min. 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. * p<0.05, ** p<0.01, compared to sham group as indicated by brackets, Kruskal Wallis test with Benjamini Yekutieli correction. 21 Those with congestive heart failure may also fare better because of Arch Dis Child Fetal Neonatal Ed. We had six animals in each 24-h group (TBI control; TBI xenon; sham surgery) and four animals in the primary injury group. Your Xenon Team. No! Sleep. Subsequently my fatigue 2008;26(2):40926. 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. 1a(i),(ii), b(i), representing a 2.7-fold increase. Images of the footprints are recorded by a video camera under the walkway. Nintedanib in Progressive Fibrosing Interstitial Lung In the left and right CA1 and DG hippocampal subregions, and in the left CA3 subregion there was a significant (p<0.05) increase in median number of microglia in the xenon-treated group compared to the sham group (Fig.