School of Biomedical Engineering and Sciences, Virginia Polytechnic and State University, Blacksburg, VA, USA.
Department of Psychiatry and Behavioral Neurosciences, Wayne State University School of Medicine, Detroit MI.
Mol Cell Neurosci. 2014 Mar;59:119-26. doi: 10.1016/j.mcn.2014.02.004. Epub 2014 Feb 15.
Working memory, which is dependent on higher-order executive function in the prefrontal cortex, is often disrupted in patients exposed to blast overpressure. In this study, we evaluated working memory and medial prefrontal neurochemical status in a rat model of blast neurotrauma. Adult male Sprague-Dawley rats were anesthetized with 3% isoflurane and exposed to calibrated blast overpressure (17 psi, 117 kPa) while sham animals received only anesthesia. Early neurochemical effects in the prefrontal cortex included a significant decrease in betaine (trimethylglycine) and an increase in GABA at 24 h, and significant increases in glycerophosphorylcholine, phosphorylethanolamine, as well as glutamate/creatine and lactate/creatine ratios at 48 h. Seven days after blast, only myo-inositol levels were altered showing a 15% increase. Compared to controls, short-term memory in the novel object recognition task was significantly impaired in animals exposed to blast overpressure. Working memory in control animals was negatively correlated with myo-inositol levels (r=-.759, p<0.05), an association that was absent in blast exposed animals. Increased myo-inositol may represent tardive glial scarring in the prefrontal cortex, a notion supported by GFAP changes in this region after blast overexposure as well as clinical reports of increased myo-inositol in disorders of memory.
工作记忆依赖于前额叶皮层的高级执行功能，在暴露于爆炸超压的患者中经常受到干扰。在这项研究中，我们评估了爆炸神经创伤大鼠模型中的工作记忆和内侧前额叶神经化学状态。成年雄性 Sprague-Dawley 大鼠在 3%异氟烷麻醉下暴露于校准的爆炸超压（17 psi，117 kPa），而假手术动物仅接受麻醉。前额叶皮层中的早期神经化学效应包括甜菜碱（三甲甘氨酸）显著减少和 GABA 在 24 小时时增加，以及甘油磷酸胆碱、磷酸乙醇胺以及谷氨酸/肌酸和乳酸/肌酸比值在 48 小时时显著增加。爆炸后 7 天，只有肌醇水平发生改变，显示增加了 15%。与对照组相比，暴露于爆炸超压的动物在新物体识别任务中的短期记忆明显受损。对照动物的工作记忆与肌醇水平呈负相关（r=-.759，p<0.05），而在暴露于爆炸的动物中则没有这种关联。肌醇的增加可能代表前额叶皮层中的迟发性神经胶质瘢痕形成，这一观点得到了该区域在爆炸超暴露后 GFAP 变化以及记忆障碍中肌醇增加的临床报告的支持。
