Vigabatrin is the drug of choice in resistant epilepsy and infantile spasms. Ataxia, tremors, and abnormal gait have been frequently reported following its use indicating cerebellar involvement. This study aimed, for the first time, to investigate the involvement of necroptosis and apoptosis in the VG-induced cerebellar cell loss and the possible protective role of combined omega-3 and vitamin B12 supplementation. Fifty Sprague-Dawley adult male rats (160-200 g) were divided into equal five groups: the control group received normal saline, VG200 and VG400 groups received VG (200 mg or 400 mg/kg, respectively), VG200 + OB and VG400 + OB groups received combined VG (200 mg or 400 mg/kg, respectively), vitamin B12 (1 mg/kg), and omega-3 (1 g/kg). All medications were given daily by gavage for four weeks. Histopathological changes were examined in H&E and luxol fast blue (LFB) stained sections. Immunohistochemical staining for caspase-3 and receptor-interacting serine/threonine-protein kinase-1 (RIPK1) as well as quantitative real-time polymerase chain reaction (qRT-PCR) for myelin basic protein (MBP), caspase-3, and receptor-interacting serine/threonine-protein kinase-3 (RIPK3) genes were performed. VG caused a decrease in the granular layer thickness and Purkinje cell number, vacuolations, demyelination, suppression of MBP gene expression, and induction of caspases-3, RIPK1, and RIPK3 in a dose-related manner. Combined supplementation with B12 and omega-3 improved the cerebellar histology, increased MBP, and decreased apoptotic and necroptotic markers. In conclusion, VG-induced neuronal cell loss is dose-dependent and related to both apoptosis and necroptosis. This could either be ameliorated (in low-dose VG) or reduced (in high-dose VG) by combined supplementation with B12 and omega-3.

氨己烯酸是抗性癫痫和婴儿痉挛的首选药物。使用后经常报告共济失调、震颤和步态异常，表明小脑受累。本研究首次旨在调查坏死性凋亡和细胞凋亡在 VG 诱导的小脑细胞损失中的作用，以及联合补充 omega-3 和维生素 B12 的可能保护作用。将 50 只 Sprague-Dawley 成年雄性大鼠（160-200 g）分成相等的五组：对照组给予生理盐水，VG200 和 VG400 组给予 VG（分别为 200 mg 或 400 mg/kg），VG200 + OB 和 VG400 + OB 组接受联合 VG（分别为 200 mg 或 400 mg/kg）、维生素 B12（1 mg/kg）和 omega-3（1 g/kg）。每天通过管饲法给予所有药物，持续四个星期。在 H&E 和 luxol fast blue (LFB) 染色切片中检查组织病理学变化。caspase-3 和受体相互作用的丝氨酸/苏氨酸蛋白激酶-1 (RIPK1) 的免疫组织化学染色以及髓鞘碱性蛋白 (MBP)、caspase-3 和受体的定量实时聚合酶链反应 (qRT-PCR) -进行了相互作用的丝氨酸/苏氨酸蛋白激酶3 (RIPK3)基因。VG 以剂量相关的方式导致颗粒层厚度和浦肯野细胞数量减少、空泡形成、脱髓鞘、MBP 基因表达抑制以及 caspase-3、RIPK1 和 RIPK3 的诱导。联合补充 B12 和 omega-3 可改善小脑组织学，增加 MBP，并减少凋亡和坏死性凋亡标志物。综上所述，VG 诱导的神经元细胞丢失是剂量依赖性的，并且与细胞凋亡和坏死性凋亡有关。这可以通过联合补充 B12 和 omega-3 来改善（在低剂量 VG 中）或减少（在高剂量 VG 中）。