Park Kellie, Biederer Thomas
Department of Anesthesiology, Yale University School of Medicine, New Haven, CT, USA.
Department of Molecular Biophysics & Biochemistry, Yale University School of Medicine, New Haven, CT, USA ; Program in Cellular Neuroscience, Neurodegeneration & Repair, Yale University School of Medicine, New Haven, CT, USA.
Future Neurol. 2013 Sep;8(5):555-567. doi: 10.2217/fnl.13.35.
Few specific therapeutic targets exist to manage brain injury, despite the prevalence of stroke or traumatic brain injury. With traumatic brain injury, characteristic neuronal changes include axonal swelling and degeneration, and the loss of synapses, the sites of communication between neurons. This is followed by axonal sprouting and alterations in synaptic markers in recovery. The resulting changes in neuronal connectivity are likely to contribute to the effects of traumatic brain injury on cognitive functions and the underlying mechanisms may represent points of therapeutic intervention. In agreement, animal studies implicate adhesion and signaling molecules that organize synapses as molecular players in neuronal recovery. In this article, the authors focus on the role of cell surface interactions in the recovery after brain injury in humans and animals. The authors review cellular and synaptic alterations that occur with injury and how changes in cell adhesion, protein expression and modification may be involved in recovery. The changes in neuronal surface interactions as potential targets and their possible value for the development of therapeutics are also discussed.
尽管中风或创伤性脑损伤很常见,但治疗脑损伤的特异性治疗靶点却很少。对于创伤性脑损伤,典型的神经元变化包括轴突肿胀和变性,以及突触(神经元之间的通讯位点)的丧失。随后在恢复过程中会出现轴突发芽和突触标志物的改变。神经元连接性的这些变化可能导致创伤性脑损伤对认知功能产生影响,其潜在机制可能代表了治疗干预的要点。与此一致的是,动物研究表明,作为神经元恢复过程中的分子参与者,那些构建突触的黏附分子和信号分子发挥了作用。在本文中,作者聚焦于细胞表面相互作用在人类和动物脑损伤后恢复过程中的作用。作者回顾了损伤时发生的细胞和突触改变,以及细胞黏附、蛋白质表达和修饰的变化可能如何参与恢复过程。还讨论了作为潜在靶点的神经元表面相互作用的变化及其在治疗开发中的可能价值。