F.M. Kirby Neurobiology Center, Boston Children's Hospital and Harvard Medical School, Boston, MA, 02115, USA.
Cellular Neuroscience, Neurodegeneration and Repair Program, Departments of Neurology and Neuroscience, Yale University School of Medicine, New Haven, CT, 06520, USA.
Mol Neurobiol. 2019 Jun;56(6):3948-3957. doi: 10.1007/s12035-018-1349-5. Epub 2018 Sep 19.
Axotomy results in permanent loss of function after brain and spinal cord injuries due to the minimal regenerative propensity of the adult central nervous system (CNS). To identify pharmacological enhancers of axon regeneration, 960 compounds were screened for cortical neuron axonal regrowth using an in vitro cortical scrape assay. Diltiazem, verapamil, and bromopride were discovered to facilitate axon regeneration in rat cortical cultures, in the presence of chondroitin sulfate proteoglycans (CSPGs). Diltiazem, an L-type calcium channel blocker (L-CCB), also promotes axon outgrowth in adult primary mouse dorsal root ganglion (DRG) and induced human sensory (iSensory) neurons.
轴突切断会导致脑和脊髓损伤后的永久性功能丧失,这是由于成人中枢神经系统(CNS)的再生能力极弱所致。为了鉴定促进轴突再生的药物,使用体外皮质刮擦测定法筛选了 960 种化合物以促进皮质神经元轴突再生。发现地尔硫卓、维拉帕米和溴必利在软骨素硫酸盐蛋白聚糖(CSPG)存在的情况下有利于大鼠皮质培养物中的轴突再生。地尔硫卓是一种 L 型钙通道阻滞剂(L-CCB),也可促进成年原发性小鼠背根神经节(DRG)中的轴突生长,并诱导人感觉神经元(iSensory 神经元)。