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1.
Crit Care ; 24(1): 667, 2020 11 27.
Artigo em Inglês | MEDLINE | ID: mdl-33246487

RESUMO

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 neuroinflammation 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% nitrogen: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 neuroprotective effect. These findings suggest that xenon may be a first-line clinical treatment for brain trauma.


Assuntos
Inflamação , Locomoção , Neurônios , Xenônio , Animais , Masculino , Encéfalo/patologia , Encéfalo/fisiopatologia , Lesões Encefálicas Traumáticas , Modelos Animais de Doenças , Inflamação/tratamento farmacológico , Inflamação/prevenção & controle , Locomoção/efeitos dos fármacos , Neurônios/efeitos dos fármacos , Neurônios/patologia , Fármacos Neuroprotetores/farmacologia , Fármacos Neuroprotetores/uso terapêutico , Avaliação de Resultados em Cuidados de Saúde/métodos , Ratos Sprague-Dawley/fisiologia , Xenônio/farmacologia , Xenônio/uso terapêutico
2.
Br J Anaesth ; 123(1): 60-73, 2019 07.
Artigo em Inglês | MEDLINE | ID: mdl-31122738

RESUMO

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% O2) or control gas (75% N2:25% O2). 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.


Assuntos
Lesões Encefálicas Traumáticas/complicações , Encéfalo/fisiopatologia , Transtornos Cognitivos/prevenção & controle , Inflamação/prevenção & controle , Neurônios/efeitos dos fármacos , Xenônio/uso terapêutico , Animais , Encéfalo/efeitos dos fármacos , Doença Crônica , Cognição , Transtornos Cognitivos/etiologia , Modelos Animais de Doenças , Seguimentos , Inflamação/etiologia , Masculino , Camundongos , Camundongos Endogâmicos C57BL , Fármacos Neuroprotetores , Análise de Sobrevida
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