Persistent working memory dysfunction following traumatic brain injury: evidence for a time-dependent mechanism.
Persistent working memory dysfunction following traumatic brain injury: evidence for a time-dependent mechanism.
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DOI：
10.1016/j.neuroscience.2008.12.050
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发表时间：
2009-03-17
期刊：
影响因子：
3.3
通讯作者：
Dash PK
中科院分区：
文献类型：
--
作者：
Hoskison MM;Moore AN;Hu B;Orsi S;Kobori N;Dash PK
前额叶皮层非常容易受到创伤性脑损伤的影响，导致许多高级认知和执行功能的功能障碍，如计划，信息处理速度，语言，记忆，注意力和感知。所有这些过程都需要一定程度的工作记忆。有趣的是，在许多情况下，损伤后的工作记忆缺陷可以在前额叶皮层没有明显损伤的情况下出现。最近，过量GABA介导的前额叶神经元活性抑制已被确定为一个贡献者的工作记忆功能障碍的第一个月内皮层撞击损伤的大鼠。然而，还没有检查这些工作记忆缺陷是否持续存在，如果是这样，它们是否仍然适合通过GABA拮抗剂治疗。我们的研究结果表明，工作记忆功能障碍，评估使用延迟匹配到位置和延迟交替t迷宫任务，在外侧皮质撞击损伤后持续至少16周。这些赤字被发现不再是GABA介导的过度抑制内侧前额叶皮层神经元活动的直接结果。高尔基体染色的前边缘锥体神经元显示，TBI导致一个显着的缩短层V/VI基底树突乔木损伤后4个月，以及在这些神经元的基底和顶端棘的密度增加。在损伤后14天的动物中未观察到这些变化，在该时间点，施用GABA受体拮抗剂改善工作记忆功能。综上所述，本研究结果，沿着与以前发表的报告，表明时间的考虑，必须考虑到设计时，机制为基础的治疗，以改善工作记忆功能的TBI患者。
The prefrontal cortex is highly vulnerable to traumatic brain injury resulting in the dysfunction of many high-level cognitive and executive functions such as planning, information processing speed, language, memory, attention, and perception. All of these processes require some degree of working memory. Interestingly, in many cases, post-injury working memory deficits can arise in the absence of overt damage to the prefrontal cortex. Recently, excess GABA-mediated inhibition of prefrontal neuronal activity has been identified as a contributor to working memory dysfunction within the first month following cortical impact injury of rats. However, it has not been examined if these working memory deficits persist, and if so, whether they remain amenable to treatment by GABA antagonism. Our findings show that working memory dysfunction, assessed using both the delay match-to-place and delayed alternation t-maze tasks, following lateral cortical impact injury persists for at least 16 weeks post-injury. These deficits were found to be no longer the direct result of excess GABA-mediated inhibition of medial prefrontal cortex neuronal activity. Golgi staining of prelimbic pyramidal neurons revealed that TBI causes a significant shortening of layer V/VI basal dendrite arbors by 4 months post-injury, as well as an increase in the density of both basal and apical spines in these neurons. These changes were not observed in animals 14 days-post-injury, a time point at which administration of GABA receptor antagonists improves working memory function. Taken together, the present findings, along with previously published reports, suggest that temporal considerations must be taken into account when designing mechanism-based therapies to improve working memory function in TBI patients.
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