Yokohama City University Graduate School of Medicine, Department of Physiology, Yokohama, 236-0004, Japan.
Human Informatics Research Institute, National Institute of Advanced Industrial Science and Technology, Ibaraki, 305-8568, Japan.
Science. 2018 Apr 6;360(6384):50-57. doi: 10.1126/science.aao2300.
Brain damage such as stroke is a devastating neurological condition that may severely compromise patient quality of life. No effective medication-mediated intervention to accelerate rehabilitation has been established. We found that a small compound, edonerpic maleate, facilitated experience-driven synaptic glutamate AMPA (α-amino-3-hydroxy-5-methyl-4-isoxazole-propionic-acid) receptor delivery and resulted in the acceleration of motor function recovery after motor cortex cryoinjury in mice in a training-dependent manner through cortical reorganization. Edonerpic bound to collapsin-response-mediator-protein 2 (CRMP2) and failed to augment recovery in CRMP2-deficient mice. Edonerpic maleate enhanced motor function recovery from internal capsule hemorrhage in nonhuman primates. Thus, edonerpic maleate, a neural plasticity enhancer, could be a clinically potent small compound with which to accelerate rehabilitation after brain damage.
脑损伤，如中风，是一种破坏性的神经疾病，可能严重影响患者的生活质量。目前还没有有效的药物干预来加速康复。我们发现一种小分子化合物，依多尼培马来酸酯，通过皮层重组，以训练依赖的方式促进经验驱动的突触谷氨酸 AMPA（α-氨基-3-羟基-5-甲基-4-异恶唑丙酸）受体的传递，从而加速运动皮层冷冻损伤后小鼠的运动功能恢复。依多尼培与塌陷反应介质蛋白 2（CRMP2）结合，并且在 CRMP2 缺陷型小鼠中不能增强恢复。依多尼培马来酸酯增强了非人灵长类动物内囊出血后的运动功能恢复。因此，作为一种神经可塑性增强剂，依多尼培马来酸酯可能是一种具有临床潜力的小分子化合物，可以加速脑损伤后的康复。
