Morawska Marta M, Büchele Fabian, Moreira Carlos Goncalves, Imbach Lukas L, Noain Daniela, Baumann Christian R
Department of Neurology, University Hospital of Zurich, 8091 Zurich, Switzerland
Department of Neurology, University Hospital of Zurich, 8091 Zurich, Switzerland.
J Neurosci. 2016 Mar 23;36(12):3422-9. doi: 10.1523/JNEUROSCI.3274-15.2016.
Traumatic brain injury (TBI) is a major cause of death and disability worldwide. It produces diffuse axonal injury (DAI), which contributes to cognitive impairment, but effective disease-modifying treatment strategies are missing. We have recently developed a rat model of closed skull TBI that reproduces human TBI consequences, including DAI and clinical sequelae such as memory impairment. Here, we investigated whether sleep modulation after trauma has an impact on DAI and memory outcome. We assessed cognition with the novel object recognition test and stained for amyloid precursor protein, a DAI marker. We found that both sleep induction and restriction acutely after TBI enhanced encephalographic slow-wave activity, markedly reduced diffuse axonal damage in the cortex and hippocampus, and improved memory impairment 2 weeks after trauma. These results suggest that enhancing slow-wave sleep acutely after trauma may have a beneficial disease-modifying effect in subjects with acute TBI.
Traumatic brain injury (TBI) is a clinically important entity. Cognitive deficits belong to the most prevalent chronic posttraumatic symptoms, most likely due to diffuse axonal injury (DAI). A growing body of evidence suggests a role of sleep in the clearance of waste products in the brain, possibly including amyloid precursor protein (APP), a marker of DAI. In this study, we provide evidence that enhancement of slow-wave oscillatory activity in the delta-frequency range decreases the APP-immunoreactivity and preserves cognitive abilities after trauma, potentially offering novel, noninvasive treatment options for traumatic injury.
创伤性脑损伤（TBI）是全球范围内死亡和残疾的主要原因。它会导致弥漫性轴索损伤（DAI），进而导致认知障碍，但目前缺乏有效的疾病改善治疗策略。我们最近开发了一种闭合性颅脑创伤大鼠模型，该模型再现了人类TBI的后果，包括DAI和记忆障碍等临床后遗症。在此，我们研究了创伤后睡眠调节是否会对DAI和记忆结果产生影响。我们通过新颖物体识别测试评估认知，并对淀粉样前体蛋白（一种DAI标志物）进行染色。我们发现，TBI后立即进行睡眠诱导和睡眠限制均可增强脑电图慢波活动，显著减少皮质和海马体中的弥漫性轴索损伤，并改善创伤后2周的记忆障碍。这些结果表明，创伤后立即增强慢波睡眠可能对急性TBI患者具有有益的疾病改善作用。
创伤性脑损伤（TBI）是一个具有临床重要性的疾病实体。认知缺陷是最常见的慢性创伤后症状，很可能是由于弥漫性轴索损伤（DAI）所致。越来越多的证据表明，睡眠在清除大脑中的废物（可能包括DAI标志物淀粉样前体蛋白（APP））方面发挥作用。在本研究中，我们提供的证据表明，增强δ频段的慢波振荡活动可降低APP免疫反应性，并在创伤后保留认知能力，这可能为创伤性损伤提供新的非侵入性治疗选择。
