Barry Jeremy M, Choy ManKin, Dube Celine, Robbins Ashlee, Obenaus Andre, Lenck-Santini Pierre Pascal, Scott Rod C, Baram Tallie Z, Holmes Gregory L
Department of Neurological Sciences, University of Vermont College of Medicine, Burlington, VT, United States; Department of Neurology, Geisel School of Medicine at Dartmouth, Hanover, NH, United States.
Department of Neurology, University of California-Irvine, Irvine, CA, United States.
Exp Neurol. 2015 Jul;269:242-52. doi: 10.1016/j.expneurol.2015.04.015. Epub 2015 May 1.
Evidence from animal models and patient data indicates that febrile status epilepticus (FSE) in early development can result in permanently diminished cognitive abilities. To understand the variability in cognitive outcome following FSE, we used MRI to measure dynamic brain metabolic responses to the induction of FSE in juvenile rats. We then compared these measurements to the ability to learn an active avoidance spatial task weeks later. T2 relaxation times were significantly lower in FSE rats that were task learners in comparison to FSE non-learners. While T2 time in whole brain held the greatest predictive power, T2 in hippocampus and basolateral amygdala were also excellent predictors. These signal differences in response to FSE indicate that rats that fail to meet metabolic and oxygen demand are more likely to develop spatial cognition deficits. Place cells from FSE non-learners had significantly larger firing fields and higher in-field firing rate than FSE learners and control animals and imply increased excitability in the pyramidal cells of FSE non-learners. These findings suggest a mechanistic cause for the spatial memory deficits in active avoidance and are relevant to other acute neurological insults in early development where cognitive outcome is a concern.
来自动物模型和患者数据的证据表明,早期发育阶段的热性惊厥持续状态(FSE)可导致认知能力永久性下降。为了解FSE后认知结果的变异性,我们使用MRI来测量幼鼠FSE诱导后的动态脑代谢反应。然后,我们将这些测量结果与数周后学习主动回避空间任务的能力进行比较。与FSE非学习者相比,作为任务学习者的FSE大鼠的T2弛豫时间显著更低。虽然全脑T2时间具有最大的预测能力,但海马体和基底外侧杏仁核的T2时间也是优秀的预测指标。这些对FSE反应的信号差异表明,未能满足代谢和氧气需求的大鼠更有可能出现空间认知缺陷。FSE非学习者的位置细胞的放电场明显更大,场内放电率高于FSE学习者和对照动物,这意味着FSE非学习者的锥体细胞兴奋性增加。这些发现提示了主动回避中空间记忆缺陷的机制原因,并且与早期发育中其他急性神经损伤相关,在这些损伤中认知结果是一个关注点。