Dynamic Interaction between Cortico-Brainstem Pathways during Training-Induced Recovery in Stroke Model Rats
Dynamic Interaction between Cortico-Brainstem Pathways during Training-Induced Recovery in Stroke Model Rats
复制标题
DOI：
10.1523/jneurosci.0649-19.2019
复制
发表时间：
2019-09-11
影响因子：
5.3
通讯作者：
Hida, Hideki
中科院分区：
文献类型：
--
作者：
Ishida, Akimasa;Kobayashi, Kenta;Hida, Hideki
残留下行运动回路的重组是卒中后恢复的基础。我们先前阐明了皮质红束与内囊出血(ICH)后密集肢体使用导致的功能恢复之间的因果关系。然而，其他下降束，如皮质网状束，也可能参与康复诱导的代偿。为了研究脑出血后康复诱导的康复是否涉及代偿回路从皮质红斑束转移到皮质网状束，我们使用两组病毒载体建立了皮质红斑束或/和皮质网状束的功能丧失，这两组病毒载体包括Tet-on系统和由设计者药物系统独有激活的设计者受体。我们使用了一种脑出血模型，破坏了近60%的皮质分离纤维。对康复大鼠的顺行追踪显示，在康复早期，运动皮质在红核的轴突大量萌发，而延髓网状结构的轴突则不多。皮质红束的这一主要贡献表现为选择性阻断，而选择性抑制鳕鱼-网状束的作用甚微。有趣的是，自康复开始时，皮质红束阻断导致网状结构内轴突出芽明显增加，功能实质上恢复。在皮质红束阻断下，额外的皮质网状束沉默显著地恶化了恢复的前肢功能。此外，皮质网状束沉默可导致皮质网状束明显的运动障碍，皮质网状束的替代募集是在皮质红束阻断下的密集肢体运动逐渐引起的。这些发现表明，个别皮质-脑干通路具有动态代偿能力，以支持脑出血后康复功能的恢复。
Reorganization of residual descending motor circuits underlies poststroke recovery. We previously clarified a causal relationship between the cortico-rubral tract and intensive limb use-induced functional recovery after internal capsule hemorrhage (ICH). However, other descending tracts, such as the cortico-reticular tract, might also be involved in rehabilitation-induced compensation. To investigate whether rehabilitation-induced recovery after ICH involves a shift in the compensatory circuit from the cortico-rubral tract to the cortico-reticular tract, we established loss of function of the cortico-rubral tract or/and cortico-reticular tract using two sets of viral vectors comprising the Tet-on system and designer receptors exclusively activated by the designer drug system. We used an ICH model that destroyed almost 60% of the corticofugal fibers. Anterograde tracing in rehabilitated rats revealed abundant sprouting of axons from the motor cortex in the red nucleus but not in the medullary reticular formation during the early phase of recovery. This primary contribution of the cortico-rubral tract was demonstrated by its selective blockade, whereas selective cod ico-reticular tract silencing had little effect. Interestingly, cortico-rubral tract blockade from the start of rehabilitation induced an obvious increase of axon sprouting in the reticular formation with substantial functional recovery. Additional cortico-reticular tract silencing under the cortico-rubral tract blockade significantly worsened the recovered forelimb function. Furthermore, the alternative recruitment of the cortico-reticular tract was gradually induced by intensive limb use under cortico-rubral tract blockade, in which cortico-reticular tract silencing caused an apparent motor deficit. These findings indicate that individual cortico-brainstem pathways have dynamic compensatory potency to support rehabilitative functional recovery after ICH.