PDF(Pubmed)
Abstract：
A neurological dogma is that the contralateral effects of brain injury are set through crossed descending neural tracts. We have recently identified a novel topographic neuroendocrine system (T-NES) that operates via a humoral pathway and mediates the left-right side-specific effects of unilateral brain lesions. In rats with completely transected thoracic spinal cords, unilateral injury to the sensorimotor cortex produced contralateral hindlimb flexion, a proxy for neurological deficit. Here, we investigated in acute experiments whether T-NES consists of left and right counterparts and whether they differ in neural and molecular mechanisms. We demonstrated that left- and right-sided hormonal signaling is differentially blocked by the δ-, κ- and µ-opioid antagonists. Left and right neurohormonal signaling differed in targeting the afferent spinal mechanisms. Bilateral deafferentation of the lumbar spinal cord abolished the hormone-mediated effects of the left-brain injury but not the right-sided lesion. The sympathetic nervous system was ruled out as a brain-to-spinal cord-signaling pathway since hindlimb responses were induced in rats with cervical spinal cord transections that were rostral to the preganglionic sympathetic neurons. Analysis of gene-gene co-expression patterns identified the left- and right-side-specific gene co-expression networks that were coordinated via the humoral pathway across the hypothalamus and lumbar spinal cord. The coordination was ipsilateral and disrupted by brain injury. These findings suggest that T-NES is bipartite and that its left and right counterparts contribute to contralateral neurological deficits through distinct neural mechanisms, and may enable ipsilateral regulation of molecular and neural processes across distant neural areas along the neuraxis.
摘要：
神经系统的教条是，脑损伤的对侧作用是通过交叉的下降神经束设定的。我们最近确定了一种新型的地形图神经内分泌系统（T-NES），该系统通过体液途径起作用，并介导单侧脑部病变的左右两侧特异性作用。在胸脊髓完全横断的大鼠中，对后肢感觉运动皮层的单侧损伤产生了后肢姿势不对称，对侧后肢屈曲，神经缺陷的代理。这里,我们在急性实验中研究了T-NES是否由左和右对应物组成，以及它们在神经和分子机制及其运行模式上是否不同，相对于脑损伤侧可能是同侧或对侧。我们证明了左侧和右侧激素信号传导被选择性阿片样物质拮抗剂不同地阻断。左脑病变的作用被δ-和κ-阿片受体拮抗剂抑制，而右脑病变的患者被µ-阿片拮抗剂抑制。左右神经激素信号在靶向传入脊髓机制方面有所不同。腰脊髓的双侧脱脂消除了左脑损伤而不是右侧病变的激素介导的作用。交感神经系统被排除为大脑到脊髓的信号传导途径，因为后肢反应是在颈脊髓横断的大鼠中引起的，而颈脊髓横断是向节前交感神经元的。基因-基因共表达模式分析确定了左侧和右侧特异性基因调控网络，这些网络通过穿过下丘脑和腰脊髓的体液途径进行协调。协调是同侧的，并因脑损伤而中断。这些发现表明T-NES是双向的，它的左右对应物通过不同的神经机制导致对侧神经功能缺损，并且可以实现沿神经轴的远处神经区域的分子和神经过程的同侧调节。
