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

被引:52
作者
Campos-Pires, Rita [1 ,2 ,3 ]
Hirnet, Tobias [4 ]
Valeo, Flavia [1 ]
Ong, Bee Eng [1 ]
Radyushkin, Konstantin [5 ]
Aldhoun, Jitka [1 ]
Saville, Joanna [1 ]
Edge, Christopher J. [6 ,7 ]
Franks, Nicholas P. [6 ]
Thal, Serge C. [4 ]
Dickinson, Robert [1 ,2 ]
机构
[1] Dept Surg & Canc, Anaesthet Pain Med & Intens Care Sect, London, England
[2] Imperial Coll London, Royal British Leg Ctr Blast Injury Studies, Dept Bioengn, London, England
[3] Imperial Coll Healthcare NHS Trust, Charing Cross Hosp, Intens Care Unit, Crit Care Directorate, London, England
[4] Johannes Gutenberg Univ Mainz, Dept Anaesthesiol, Med Ctr, Mainz, Germany
[5] Johannes Gutenberg Univ Mainz, Mouse Behav Outcome Unit, Focus Program Translat Neurosci, Mainz, Germany
[6] Imperial Coll London, Dept Life Sci, London, England
[7] Royal Berkshire Hosp NHS Fdn Trust, Dept Anaesthet, Reading, Berks, England
基金
英国医学研究理事会;
关键词
hippocampus; general anaesthesia; memory disorders; nerve degeneration; neuroinflammation; neuroprotection; traumatic brain injury; D-ASPARTATE RECEPTOR; WHITE-MATTER DAMAGE; COMPETITIVE-INHIBITION; INHALED XENON; BUPRENORPHINE; HYPOPITUITARISM; EPIDEMIOLOGY; HYPOTHERMIA; ANALGESIA; PATHOLOGY;
D O I
10.1016/j.bja.2019.02.032
中图分类号
R614 [麻醉学];
学科分类号
100217 ;
摘要
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.
引用
收藏
页码:60 / 73
页数:14
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