Regional neurodegeneration and gliosis are amplified by mild traumatic brain injury repeated at 24-hour intervals.

Regional neurodegeneration and gliosis are amplified by mild traumatic brain injury repeated at 24-hour intervals.
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DOI:
10.1097/nen.0000000000000115
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发表时间:
2014-10
影响因子:
3.2
通讯作者:
Saatman KE
Saatman KE
中科院分区:
医学4区
文献类型:
--
作者:
Bolton AN;Saatman KE

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每年发生的大多数创伤性脑损伤(TBI)都被归类为“轻度”。参与高风险活动的个人可能会持续多个轻微的脑外伤。我们在小鼠模型中评估了轻度脑损伤的急性生理和组织病理学后果,比较了24或48小时损伤间隔的假损伤、单次撞击或5次撞击。单次闭合性颅骨撞击导致双侧海马区和内嗅区皮质胶质细胞增厚,与撞击深度成正比。中线撞击的深度略高于阈值,导致一过性意识丧失,偶尔会导致轴突损伤,内嗅皮层和小脑中的神经元变性,并伴有星形胶质细胞增生。每24小时重复一次的轻度颅脑损伤导致双侧内嗅皮层的出血性损害,并显著增加神经变性和小胶质细胞的激活,尽管呼吸暂停和昏迷的持续时间缩短,随后的影响。双侧小脑和脑干也可见星形胶质细胞增厚和弥漫性轴索损伤。当轻度脑损伤之间的间隔增加到48小时时,其病理后果与单个脑损伤相当。综上所述,这些数据表明,在小鼠中,轻度脑损伤后24小时内,尽管对随后的轻微撞击的急性生理反应降低,但大脑仍面临更高的损伤风险。
Most traumatic brain injuries (TBIs) that occur every year are classified as ‘mild’. Individuals involved in high-risk activities may sustain multiple mild TBIs. We evaluated the acute physiological and histopathological consequences of mild TBI in a mouse model, comparing sham injury, single impact, or 5 impacts at a 24- or 48-hour inter-injury interval. A single closed skull impact resulted in bilateral gliosis in the hippocampus and entorhinal cortex that was proportional to impact depth. Midline impact, at a depth just above the threshold to induce transient unconsciousness, produced occasional axonal injury and degenerating neurons accompanied by astrogliosis in the entorhinal cortex and cerebellum. Mild TBI repeated every 24 hours resulted in bilateral hemorrhagic lesions in the entorhinal cortex along with significantly increased neurodegeneration and microglial activation despite diminished durations of apnea and unconsciousness with subsequent impacts. Astrogliosis and diffusely distributed axonal injury were also observed bilaterally in the cerebellum and the brainstem. When the interval between mild TBIs was increased to 48 hours, the pathological consequences were comparable to a single TBI. Together, these data suggest that in mice the brain remains at increased risk for damage for 24 hours after mild TBI despite reduced acute physiological responses to subsequent mild impacts.