Mild traumatic brain injury (mTBI) in children is a common and serious public health problem. Traditional neuroimaging findings in children who sustain mTBI are often normal, putting them at risk for repeated mTBI (rmTBI). There is a need for more sensitive imaging techniques capable of detecting subtle neurophysiological alterations after injury. We examined neurochemical and white matter changes using diffusion tensor imaging of the whole brain and proton magnetic resonance spectroscopy of the hippocampi at 7 Tesla in 18-day-old male rats at 7 days after mTBI and rmTBI. Traumatic axonal injury was assessed by beta-amyloid precursor protein accumulation using immunohistochemistry. A significant decrease in fractional anisotropy and increase in axial and radial diffusivity were observed in several brain regions, especially in white matter regions, after a single mTBI versus sham and more prominently after rmTBI. In addition, we observed accumulation of beta-amyloid precursor protein in the external capsule after mTBI and rmTBI. mTBI and rmTBI reduced the N-acetylaspartate/creatine ratio (NAA/Cr) and increased the myoinositol/creatine ratio (Ins/Cr) versus sham. rmTBI exacerbated the reduction in NAA/Cr versus mTBI. The choline/creatine (Cho/Cr) and (lipid/Macro Molecule 1)/creatine (Lip/Cr) ratios were also decreased after rmTBI versus sham. Diffusion tensor imaging findings along with the decrease in Cho and Lip after rmTBI may reflect damage to axonal membrane. NAA and Ins are altered at 7 days after mTBI and rmTBI likely reflecting neuro-axonal damage and glial response, respectively. These findings may be relevant to understanding the extent of disability following mTBI and rmTBI in the immature brain and may identify possible therapeutic targets.

中文翻译：

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未成熟大鼠重复性轻度创伤性脑损伤后 7 特斯拉的代谢和结构成像。


儿童轻度创伤性脑损伤（mTBI）是一个常见且严重的公共卫生问题。患有 mTBI 的儿童的传统神经影像学检查结果通常是正常的，这使他们面临重复 mTBI (rmTBI) 的风险。需要更灵敏的成像技术来检测损伤后细微的神经生理学变化。我们在 mTBI 和 rmTBI 后 7 天，使用全脑扩散张量成像和 7 特斯拉海马质子磁共振波谱检查了 18 日龄雄性大鼠的神经化学和白质变化。使用免疫组织化学通过β-淀粉样蛋白前体蛋白积累来评估创伤性轴突损伤。与假手术相比，在单次 mTBI 后，在几个大脑区域，特别是在白质区域，观察到分数各向异性显着降低，轴向和径向扩散率增加，而 rmTBI 后更明显。此外，我们观察到 mTBI 和 rmTBI 后外囊中 β-淀粉样前体蛋白的积累。与假手术相比，mTBI 和 rmTBI 降低了 N-乙酰天冬氨酸/肌酸比率 (NAA/Cr)，并增加了肌醇/肌酸比率 (Ins/Cr)。与 mTBI 相比，rmTBI 加剧了 NAA/Cr 的降低。与假手术相比，rmTBI 后胆碱/肌酸 (Cho/Cr) 和（脂质/大分子 1）/肌酸 (Lip/Cr) 比率也有所降低。弥散张量成像结果以及 rmTBI 后 Cho 和 Lip 的减少可能反映了轴突膜的损伤。 NAA 和 Ins 在 mTBI 和 rmTBI 后 7 天发生变化，可能分别反映神经轴突损伤和神经胶质反应。这些发现可能有助于了解未成熟大脑中 mTBI 和 rmTBI 后的残疾程度，并可能确定可能的治疗靶点。