背景:肌萎缩侧索硬化症(ALS)的特征是皮质和脊髓运动神经元的退化。尽管这种疾病的根本原因仍然难以捉摸,近年来,人们越来越关注皮质运动神经元的健康。聚焦超声结合微泡(FUS/MB)用于打开血脑屏障(BBB)提供了一种将药物输送到特定大脑区域的方法。对神经系统疾病的治疗有着重要的希望。
目的:我们的目的是探讨FUS/MB介导的奥克替林(Arc)一种具有抗炎活性的天然化合物,通过使用转基因ALS小鼠模型对大脑运动皮层区域。
方法:使用具有SOD1G93A突变的ALS小鼠模型,并进行每周两次FUS/MB处理的每日Arc给药。经过6周的治疗,通过握力评估电机性能,挂线,和攀爬杆测试。老鼠的大脑,收集脊髓和腓肠肌进行组织学染色。
结果:与仅给予电弧的小鼠相比,FUS/MB与Arc联合治疗可进一步缓解运动功能下降,伴随着改善腓肠肌的健康。此外,皮质和腰脊髓运动神经元衰竭的改善证明了显着的神经保护作用。
结论:这些初步结果表明,FUS/MB和arctiin的联合治疗对ALS疾病的神经肌肉功能具有潜在的有益作用。
BACKGROUND: Amyotrophic lateral sclerosis (ALS) is marked by the deterioration of both cortical and spinal cord motor neurons. Despite the underlying causes of the disease remain elusive, there has been a growing attention on the well-being of cortical motor neurons in recent times. Focused ultrasound combined with
microbubbles (FUS/MB) for opening the blood-brain barrier (BBB) provides a means for drug delivery to specific brain regions, holding significant promise for the treatment of neurological disorders.
OBJECTIVE: We aim to explore the outcomes of FUS/MB-mediated delivery of arctiin (Arc), a natural compound with anti-inflammatory activities, to the cerebral motor cortex area by using a transgenic ALS mouse model.
METHODS: The ALS mouse model with the SOD1G93A mutation was used and subjected to daily Arc administration with FUS/MB treatment twice a week. After six-week treatments, the motor performance was assessed by grip strength, wire hanging, and climbing-pole tests. Mouse brains, spinal cords and gastrocnemius muscle were harvested for histological staining.
RESULTS: Compared with the mice given Arc administration only, the combined treatments of FUS/MB with Arc induced further mitigation of the motor function decline, accompanied by improved health of the gastrocnemius muscle. Furthermore, notable neuroprotective effect was evidenced by the amelioration of motor neuron failure in the cortex and lumbar spinal cord.
CONCLUSIONS: These preliminary results indicated that the combined treatment of FUS/MB and arctiin exerted a potentially beneficial effect on neuromuscular function in the ALS disease.