Longitudinal Biochemical and Behavioral Alterations in a Gyrencephalic Model of Blast-Related Mild Traumatic Brain Injury.

IF 1.8 Q3 CLINICAL NEUROLOGY Neurotrauma reports Pub Date : 2024-03-14 eCollection Date: 2024-01-01 DOI:10.1089/neur.2024.0002
Shiyu Tang, Su Xu, Donna Wilder, Alexandre E Medina, Xin Li, Gary M Fiskum, Li Jiang, Venkata R Kakulavarapu, Joseph B Long, Rao P Gullapalli, Venkatasivasai Sujith Sajja
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Abstract

Blast-related traumatic brain injury (bTBI) is a major cause of neurological disorders in the U.S. military that can adversely impact some civilian populations as well and can lead to lifelong deficits and diminished quality of life. Among these types of injuries, the long-term sequelae are poorly understood because of variability in intensity and number of the blast exposure, as well as the range of subsequent symptoms that can overlap with those resulting from other traumatic events (e.g., post-traumatic stress disorder). Despite the valuable insights that rodent models have provided, there is a growing interest in using injury models using species with neuroanatomical features that more closely resemble the human brain. With this purpose, we established a gyrencephalic model of blast injury in ferrets, which underwent blast exposure applying conditions that closely mimic those associated with primary blast injuries to warfighters. In this study, we evaluated brain biochemical, microstructural, and behavioral profiles after blast exposure using in vivo longitudinal magnetic resonance imaging, histology, and behavioral assessments. In ferrets subjected to blast, the following alterations were found: 1) heightened impulsivity in decision making associated with pre-frontal cortex/amygdalar axis dysfunction; 2) transiently increased glutamate levels that are consistent with earlier findings during subacute stages post-TBI and may be involved in concomitant behavioral deficits; 3) abnormally high brain N-acetylaspartate levels that potentially reveal disrupted lipid synthesis and/or energy metabolism; and 4) dysfunction of pre-frontal cortex/auditory cortex signaling cascades that may reflect similar perturbations underlying secondary psychiatric disorders observed in warfighters after blast exposure.

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爆炸所致轻度脑损伤颅脑模型的纵向生化和行为改变
爆炸相关创伤性脑损伤(bTBI)是美军神经系统疾病的一个主要原因,也会对一些平民造成不利影响,并可能导致终生功能障碍和生活质量下降。在这些类型的伤害中,人们对长期后遗症的了解甚少,因为爆炸暴露的强度和次数各不相同,而且随后出现的一系列症状可能与其他创伤事件(如创伤后应激障碍)导致的症状重叠。尽管啮齿类动物模型提供了宝贵的见解,但人们对使用具有更接近人脑的神经解剖学特征的物种来建立损伤模型的兴趣与日俱增。为此,我们建立了雪貂脑爆炸损伤模型,雪貂会在与作战人员原发性爆炸损伤十分相似的条件下接受爆炸暴露。在这项研究中,我们使用体内纵向磁共振成像、组织学和行为评估方法,对遭受爆炸后的大脑生化、微观结构和行为特征进行了评估。在遭受爆炸的雪貂身上发现了以下变化:1) 与前额叶皮质/杏仁轴功能障碍有关的决策冲动性增强;2) 谷氨酸水平短暂升高,这与早先在创伤后亚急性阶段的发现一致,并可能与伴随的行为缺陷有关;3) 脑内 N-乙酰天冬氨酸水平异常升高,可能显示脂质合成和/或能量代谢紊乱;以及 4) 前额叶皮层/听觉皮层信号级联功能障碍,可能反映了在爆炸暴露后的战斗人员中观察到的继发性精神障碍的类似扰动。
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CiteScore
2.40
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0.00%
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审稿时长
8 weeks
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