Xenon improves long-term cognitive function, reduces neuronal loss and chronic neuroinflammation, and improves survival after traumatic brain injury in mice

Abstract

Background Xenon is a noble gas with neuroprotective properties that can improve short and long-term outcomes in young adult mice after controlled cortical impact. This follow-up study investigates the effects of xenon on very long-term outcomes and survival. Methods C57BL/6N young adult male mice ( n =72) received single controlled cortical impact or sham surgery and were treated with either xenon (75% Xe:25% O 2 ) or control gas (75% N 2 :25% O 2 ). Outcomes measured were: (i) 24 h lesion volume and neurological outcome score; (ii) contextual fear conditioning at 2 weeks and 20 months; (iii) corpus callosum white matter quantification; (iv) immunohistological assessment of neuroinflammation and neuronal loss; and (v) long-term survival. Results Xenon treatment significantly reduced secondary injury ( P <0.05), improved short-term vestibulomotor function ( P <0.01), and prevented development of very late-onset traumatic brain injury (TBI)-related memory deficits. Xenon treatment reduced white matter loss in the contralateral corpus callosum and neuronal loss in the contralateral hippocampal CA1 and dentate gyrus areas at 20 months. Xenon's long-term neuroprotective effects were associated with a significant ( P <0.05) reduction in neuroinflammation in multiple brain areas involved in associative memory, including reduction in reactive astrogliosis and microglial cell proliferation. Survival was improved significantly ( P <0.05) in xenon-treated animals compared with untreated animals up to 12 months after injury. Conclusions Xenon treatment after TBI results in very long-term improvements in clinically relevant outcomes and survival. Our findings support the idea that xenon treatment shortly after TBI may have long-term benefits in the treatment of brain trauma patients.

Metabolomics analysis of the hippocampus in a rat model of traumatic brain injury during the acute phase

“…The hippocampus is an important structure in the brain that is involved in multiple functional systems, including cognitive functions and working memory (Menon, 2016). Additionally, the hippocampus is an area of interest in TBI because investigations of its damage in TBI might improve the understanding of the neurobiological pathophysiology of TBI impairment (Bae et al, 2019;Campos-Pires et al, 2019).…”

“…ology of TBI impairment(Bae et al, 2019;Campos-Pires et al, 2019). Therefore, investigation of hippocampal metabolite alterations and their modulations associated with at the appropriate time windows of acute TBI could facilitate novel therapeutic strategies in the treatment…”

AVNP2 protects against cognitive impairments induced by C6 glioma by suppressing tumour associated inflammation in rats

“…Campos-Pires et al explored the relationship between chronic neuroinflammation and survival after traumatic brain injury in mice (Campos-Pires et al, 2019). The role of inflammation in Alzheimer disease (AD) and some psychological disorders has been studied much deeper than in other fields (Heppner et al et al, 2015;Murata et al, 2020).…”

Closed circuit xenon delivery for 72h in neonatal piglets following hypoxic insult using an ambient pressure automated control system: Development, technical evaluation and pulmonary effects

“…There is currently a large international clinical trial in progress investigating neuroprotective effects of xenon in combination with cooling after cardiac arrest, based on a favourable smaller trial [6][7][8]. It is also showing promise in pre-clinical in-vivo neuroprotection studies of other brain injury models such as sub-arachnoid haemorrhage and traumatic brain injury [9][10][11][12]. Xenon may protect other organs such as the heart [13][14][15] and kidney [16][17][18], and at present it is licensed for anesthesia in some European countries while these other possible uses are the subject of ongoing medical research.…”