Previous studies have reported that memantine presents evidence of therapeutic benefits in several animal models of ischemic stroke and neurodegenerative diseases. However, the effect of memantine on secondary damage in the ipsilateral thalamus after focal cortical infarction remains undefined. Present study investigated whether memantine has a protective effect on secondary damage in the ipsilateral thalamus after focal cerebral infarction in rats. At 24 h after distal middle cerebral artery occlusion (MCAO), rats in the memantine and vehicle groups were intraperitoneal injected with memantine and isopycnic vehicle, respectively, was once daily administered for consecutive 7 days. Infarct size was evaluated through Nissl staining and sensory decline determined using adhesive removal test. Secondary thalamic damage was assessed using Nissl staining and immunofluorescence 8 days after MCAO. Immunoboltting was used to identify tau and apoptosis-associated proteins in the ipsilateral thalamus after MCAO. Results revealed that memantine ameliorated sensory decline compared to the vehicle controls. Subsequently, tau phosphorylated at threonine 231 (p-tau-231), glycogen synthase kinase3β^pY216 (GSK3β^pY216) and protein phosphatase 2A (PP2A^pY307) were reduced by memantine, causing greater reduction in neuronal loss and inhibition of reactive astrogliosis in the ipsilateral ventroposterior thalamic nucleus (VPN) compared with the vehicle groups. In addition, increase in secondary damage-induced TUNEL-positive cells was blunted by memantine, as demonstrated by the significant reduction in expression of apoptosis-associated proteins. Our results suggest that memantine has a neuro-protective effect on secondary damage in the ipsilateral thalamus following MCAO by inhibiting the activity of GSK3β^pY216/PP2A^pY307 and down regulating the levels of p-tau-231 protein.

先前的研究已报道美金刚胺在几种缺血性中风和神经退行性疾病动物模型中显示出治疗益处的证据。然而，美金刚对局灶性皮层梗死后同侧丘脑继发性损伤的影响尚不确定。目前的研究调查了美金刚对大鼠局灶性脑梗死后同侧丘脑继发性损伤是否具有保护作用。在大脑中部远端动脉闭塞（MCAO）后24小时，每天给美金刚和媒介组的大鼠腹膜内注射美金刚和等渗媒介，连续7天。通过尼氏染色评估梗死面积，并使用脱粘剂测试确定感觉下降。MCAO 8天后，使用Nissl染色和免疫荧光法评估继发性丘脑损伤。免疫栓塞法用于鉴定MCAO后同侧丘脑中的tau和凋亡相关蛋白。结果显示，与载体对照相比，美金刚改善了感觉下降。随后，tau在苏氨酸231（p-tau-231）磷酸化，糖原合酶激酶3β美金刚胺可减少^pY216（^GSK3βpY216）和蛋白磷酸酶2A（PP2A ^pY307）的^含量，与媒介物组相比，同侧后后丘脑核（VPN）的神经元损失减少更多，并抑制反应性星形胶质变。此外，美金刚抑制了继发性损伤诱导的TUNEL阳性细胞的增加，这与凋亡相关蛋白的表达显着降低所证明。我们的结果表明，美金刚胺通过抑制^GSK3βpY216 / PP2A ^pY307的活性并下调p-tau-231蛋白的水平，对MCAO后同侧丘脑的继发性损伤具有神经保护作用。