Mitra Nilesh Kumar, Singh Nermesh Singh A/L Gurdib, Wadingasafi Nurul Ain Najihah Binti, Chellian Jestin
Human Biology Division, School of Medicine, International Medical University, Bukit Jalil 57000, Kuala Lumpur, Malaysia.
School of Pharmacy, International Medical University, Bukit Jalil 57000, Kuala Lumpur, Malaysia.
Res Pharm Sci. 2022 Jan 15;17(2):134-142. doi: 10.4103/1735-5362.335172. eCollection 2022 Apr.
Fingolimod is a sphingosine 1-phosphate receptor modulator used to treat multiple sclerosis (MS). Alpha-tocopherol (AT) has been found to improve motor function in an animal model of MS. In the present study, the effects of AT and fingolimod on the locomotor function and histological evidence of demyelination were compared in a cuprizone-induced rat model of MS.
Female Sprague-Dawley rats (8 weeks) were fed with 0.2% (w/w) cuprizone diet for 5 weeks followed by intraperitoneal injections of fingolimod (3 mg/Kg; group F, n = 10) and alpha- tocopherol (100 mg/Kg; group A, n = 10). Vehicle-treated rats (group V, n = 10) were treated intraperitoneally with 1% ethanol in saline on weeks 6 and 7. Open field and beam walking tests were carried out every 10 days. The mean area of demyelination in the corpus callosum was quantified using Luxol fast blue stained histological sections of the forebrain.
FINDINGS/RESULTS: The mean speed of movement was increased by 54% and 50% in groups F and A compared to group V. Total distance moved was increased by 61% and 52.7% in groups F and A compared to group V. Mean time to walk the beam was reduced in group A by 52% compared to group V. Mean frequency of crossing lines from the inner squares to outer squares was reduced in groups A and F compared to group V. Mean area of demyelination in corpus callosum showed 62% reduction in group A compared to group V.
Both fingolimod and AT treatments improved the locomotor function. However, AT treatment reduced the areas of demyelination in higher proportion and improved motor coordination and exploratory behavior.
芬戈莫德是一种用于治疗多发性硬化症（MS）的鞘氨醇-1-磷酸受体调节剂。已发现α-生育酚（AT）可改善MS动物模型的运动功能。在本研究中，在铜螯合剂诱导的MS大鼠模型中比较了AT和芬戈莫德对运动功能和脱髓鞘组织学证据的影响。
将雌性斯普拉格-道利大鼠（8周龄）喂食0.2%（w/w）铜螯合剂饮食5周，随后腹腔注射芬戈莫德（3mg/kg；F组，n = 10）和α-生育酚（100mg/kg；A组，n = 10）。在第6周和第7周，用生理盐水腹腔注射1%乙醇处理对照大鼠（V组，n = 10）。每10天进行旷场试验和横梁行走试验。使用前脑的Luxol固蓝染色组织切片对胼胝体中的脱髓鞘平均面积进行定量。
与V组相比，F组和A组的平均运动速度分别提高了54%和50%。与V组相比，F组和A组的总移动距离分别增加了61%和52.7%。与V组相比，A组在横梁上行走的平均时间减少了52%。与V组相比，A组和F组从内方格到外方格的交叉线平均频率降低。与V组相比，A组胼胝体中的脱髓鞘平均面积减少了62%。
芬戈莫德和AT治疗均改善了运动功能。然而，AT治疗在更大程度上减少了脱髓鞘面积，并改善了运动协调性和探索行为。
