Hoane Michael R, Lasley Laura A, Akstulewicz Stacy L
Brain Injury Laboratory, Department of Psychology and Program in Neuroscience, Rawl #217, East Carolina University, Greenville, NC 27858, USA.
Behav Brain Res. 2004 Aug 12;153(1):189-97. doi: 10.1016/j.bbr.2003.11.012.
With increasing age comes an increased risk for sustaining traumatic brain injuries (TBI). However, the effect of age is rarely studied in animal models of TBI. The present study evaluated the effect of increased age on recovery of function following bilateral medial frontal cortex injury. Groups of young (3 months) and middle-aged (14 months) rats received bilateral frontal cortex contusions or sham injuries. The rats were tested on a variety of tests to measure sensorimotor performance (bilateral tactile adhesive removal test), skilled forelimb use (staircase test), and the acquisition of reference and working memory in the Morris water maze. Results indicated that injury produced significant impairments on all behavioral tests compared to sham controls. Middle-aged rats that received cortical contusions were significantly impaired on the bilateral tactile adhesive removal test, acquisition of a reference memory task, and working memory compared to young-injured rats. Histological analysis showed that middle-aged rats developed significantly larger lesion cavities but did not show an increase in the number of glial fibrillary acidic protein (GFAP+) cells compared to young-injured rats. Age alone also significantly impaired function on the bilateral adhesive tactile removal test, skilled forelimb use, the acquisition of a reference memory task, and also increased the number of GFAP+ cells compared to young rats. These results indicate that middle-aged rats respond to brain injury differently than young rats and that age is an important factor to consider in pre-clinical efficacy studies.
随着年龄的增长,遭受创伤性脑损伤(TBI)的风险也会增加。然而,在TBI动物模型中,年龄的影响很少被研究。本研究评估了年龄增长对双侧内侧额叶皮质损伤后功能恢复的影响。将年轻(3个月)和中年(14个月)大鼠分组,分别接受双侧额叶皮质挫伤或假手术损伤。对大鼠进行了各种测试,以测量感觉运动性能(双侧触觉黏附去除试验)、熟练前肢使用(阶梯试验)以及在莫里斯水迷宫中参考记忆和工作记忆的获取情况。结果表明,与假手术对照组相比,损伤在所有行为测试中均产生了显著损伤。与年轻损伤大鼠相比,接受皮质挫伤的中年大鼠在双侧触觉黏附去除试验、参考记忆任务的获取和工作记忆方面均有显著损伤。组织学分析表明,与年轻损伤大鼠相比,中年大鼠形成的损伤腔明显更大,但胶质纤维酸性蛋白(GFAP+)细胞数量没有增加。与年轻大鼠相比,仅年龄因素也会显著损害双侧黏附触觉去除试验的功能、熟练前肢的使用、参考记忆任务的获取,并且还会增加GFAP+细胞的数量。这些结果表明,中年大鼠对脑损伤的反应与年轻大鼠不同,并且年龄是临床前疗效研究中需要考虑的一个重要因素。