Xenon treatment after severe traumatic brain injury improves locomotor outcome, reduces acute neuronal loss and enhances
- PDF / 9,708,926 Bytes
- 18 Pages / 595.276 x 790.866 pts Page_size
- 51 Downloads / 180 Views
en Access
RESEARCH
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 Rita Campos‑Pires1,2,3, Haldis Onggradito1, Eszter Ujvari1, Shughoofa Karimi1, Flavia Valeo1, Jitka Aldhoun1, Christopher J. Edge4,5, Nicholas P. Franks4 and Robert Dickinson1,2*
Abstract Background: 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. In this study, we evaluate the effect of xenon treatment on functional outcome, lesion volume, neuronal loss and neuroinflamma‑ tion after severe TBI in rats. Methods: Young adult male Sprague Dawley rats were subjected to controlled cortical impact (CCI) brain trauma or sham surgery followed by treatment with either 50% xenon:25% oxygen balance nitrogen, or control gas 75% nitro‑ gen:25% oxygen. Locomotor function was assessed using Catwalk-XT automated gait analysis at baseline and 24 h after injury. Histological outcomes were assessed following perfusion fixation at 15 min or 24 h after injury or sham procedure. Results: Xenon treatment reduced lesion volume, reduced early locomotor deficits, and attenuated neuronal loss in clinically relevant cortical and subcortical areas. Xenon treatment resulted in significant increases in Iba1-positive microglia and GFAP-positive reactive astrocytes that was associated with neuronal preservation. Conclusions: Our findings demonstrate that xenon improves functional outcome and reduces neuronal loss after brain trauma in rats. 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 xenon’s neuropro‑ tective effect. These findings suggest that xenon may be a first-line clinical treatment for brain trauma. Keywords: Xenon, Noble gases, Neuroprotection, Neurotrauma, Acquired brain injury, Neuroinflammation, Neuroglia, Locomotor deficit
*Correspondence: [email protected] 1 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 Full list of author information is available at the end of the article © The Author(s) 2020. 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. 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. If material is not included in the article’s Creative
Data Loading...
