Paradoxical Motor Recovery From a First Stroke After Induction of a Second Stroke: Reopening a Postischemic Sensitive Period.
Paradoxical Motor Recovery From a First Stroke After Induction of a Second Stroke: Reopening a Postischemic Sensitive Period.
复制标题
DOI：
10.1177/1545968315624783
复制
发表时间：
2016-09
影响因子：
4.2
通讯作者：
Krakauer JW
中科院分区：
文献类型：
--
作者：
Zeiler SR;Hubbard R;Gibson EM;Zheng T;Ng K;O'Brien R;Krakauer JW
先前的研究表明，中风后，由于可塑性增强，对训练的反应性有一段有限的时间；这一敏感期被认为是由缺血本身引起的。使用小鼠模型，我们先前已经证明，大多数训练相关的恢复发生在第一周，并归因于内侧运动前区(AGM)的重组。卒中敏感期的存在导致了一种违反直觉的预测，即第二次卒中应该重新打开这个窗口，并促进从第一次卒中完全恢复。为了验证这一预测，我们在CFA第一次中风后未完全恢复的小鼠的AGM中诱导了第二次中风。小鼠被训练来执行熟练的抓握(伸手抓握)任务，达到渐近的表现水平，之后它们在CFA接受光凝诱导的中风。在中风后延迟7天后，这些小鼠被重新训练到渐近线。然后，我们在AGM中诱导了第二次中风，并在仅延迟一天后重新训练了小鼠。在卒中后延迟7天开始训练并持续19天后，恐惧的恢复不完全。然而，年度股东大会上的第二次局灶性中风导致了9天的训练后戏剧性的反应，完全恢复到正常的表现水平。新的缺血可以重新开启对训练的高反应性的敏感期，并调解从先前的中风中完全恢复。
Prior studies have suggested that after stroke there is a time-limited period of increased responsiveness to training due to heightened plasticity; a sensitive period thought to be induced by ischemia itself. Using a mouse model we have previously shown that most training-associated recovery after a caudal forelimb area (CFA) stroke occurs in the first week and is attributable to reorganization in a medial premotor area (AGm). The existence of a stroke-induced sensitive period leads to the counterintuitive prediction that a second stroke should reopen this window and and promote full recovery from the first stroke. To test this prediction, we induced a second stroke in AGm of mice with incomplete recovery after a first stroke in CFA. Mice were trained to perform a skilled prehension (reach-to-grasp) task to an asymptotic level of performance after which they underwent photocoagulation-induced stroke in CFA. After a 7 day post-stroke delay, the mice were then retrained to asymptote. We then induced a second stroke in AGm and after only a one day delay retrained the mice. Recovery of prehension was incomplete when training was started after a 7-day post-stroke delay and continued for 19 days. However, a second focal stroke in AGm led to a dramatic response to 9 days of training with full recovery to normal levels of performance. New ischemia can re-open a sensitive period of heightened responsiveness to training and mediate full recovery from a previous stroke.