目的探讨侧脑室注射N-甲基-D-天冬氨酸受体2B(NR2B)拮抗剂Ro25-6981对大鼠脑局灶性缺血-再灌注(I-R)损伤的影响。方法60只雄性SD大鼠随机均分为四组:假手术组(S组),I-R组,I-R+Ro25-6981组(I-R+Ro组)和I-R+生理盐水组(I-R+NS组)。S组大...目的探讨侧脑室注射N-甲基-D-天冬氨酸受体2B(NR2B)拮抗剂Ro25-6981对大鼠脑局灶性缺血-再灌注(I-R)损伤的影响。方法60只雄性SD大鼠随机均分为四组:假手术组(S组),I-R组,I-R+Ro25-6981组(I-R+Ro组)和I-R+生理盐水组(I-R+NS组)。S组大鼠线栓置入颈内动脉的深度为10mm;I-R组大鼠采用线栓法阻闭大脑中动脉,2h后拔出线栓到颈外动脉给予再灌注;I-R+Ro组和I-R+NS组于缺血后2h脑室内分别注射Ro25-6981 0.1mol/L和生理盐水各5μl。于再灌注24h后行神经功能缺损评分;麻醉大鼠取脑组织,切片后用2,3,5-氯化三苯基四氮唑染色,Image Pro Plus 6.0图像处理软件计算大鼠脑梗死容积。结果与S组相比,I-R组大鼠神经功能缺陷评分增加,脑梗死容积增大(P<0.05或P<0.01);与I-R组相比,I-R+Ro组大鼠神经功能缺损评分降低,脑梗死容积减小(P<0.05或P<0.01)。结论大鼠缺血2h后脑室内注射NR2B拮抗剂Ro25-6981可以降低神经功能缺损评分、缩小脑梗死容积,对大鼠局灶性脑I-R损伤有一定保护作用。展开更多
Cortical spreading depression (CSD) is a transient synaptic excitation, followed by depression, which can propagate slowly across cortex, subcortex and retina. CSD is implicated in migraine with aura and may lead to m...Cortical spreading depression (CSD) is a transient synaptic excitation, followed by depression, which can propagate slowly across cortex, subcortex and retina. CSD is implicated in migraine with aura and may lead to migraine pain. CSD can be suppressed by inhibition of both NR2A and NR2B containing N-methyl-D-aspartic acid (NMDA) receptors. However, whether there is a synergistic effect of co-inhibition of NR2A and NR2B containing receptors on CSD remains unknown. In this study, an efficient in vitro model of migraine with intrinsic optical imaging approach was applied to address this role of co-activation of both NR2A and NR2B in CSD. The results showed that co-application of NVP-AAM077, a drug selectively targeting for NR2A and Ro 25-6981, a drug selectively targeting for NR2B containing receptors, showed synergistic inhibitory effects on propagation rate and the magnitude of CSD in a concentration dependent manner in chick retina. Inhibition of CSD propagation was also observed by a clinical acceptable drug that antagonizes both NR2A and NR2B containing receptors, memantine, at 10 μM. These data suggest that combinational use of antagonists selectively targeting NR2A and NR2B containing receptors could be a useful strategy for preventative treatment of migraine with improved efficacy with potential alleviated side effects.展开更多
文摘目的探讨侧脑室注射N-甲基-D-天冬氨酸受体2B(NR2B)拮抗剂Ro25-6981对大鼠脑局灶性缺血-再灌注(I-R)损伤的影响。方法60只雄性SD大鼠随机均分为四组:假手术组(S组),I-R组,I-R+Ro25-6981组(I-R+Ro组)和I-R+生理盐水组(I-R+NS组)。S组大鼠线栓置入颈内动脉的深度为10mm;I-R组大鼠采用线栓法阻闭大脑中动脉,2h后拔出线栓到颈外动脉给予再灌注;I-R+Ro组和I-R+NS组于缺血后2h脑室内分别注射Ro25-6981 0.1mol/L和生理盐水各5μl。于再灌注24h后行神经功能缺损评分;麻醉大鼠取脑组织,切片后用2,3,5-氯化三苯基四氮唑染色,Image Pro Plus 6.0图像处理软件计算大鼠脑梗死容积。结果与S组相比,I-R组大鼠神经功能缺陷评分增加,脑梗死容积增大(P<0.05或P<0.01);与I-R组相比,I-R+Ro组大鼠神经功能缺损评分降低,脑梗死容积减小(P<0.05或P<0.01)。结论大鼠缺血2h后脑室内注射NR2B拮抗剂Ro25-6981可以降低神经功能缺损评分、缩小脑梗死容积,对大鼠局灶性脑I-R损伤有一定保护作用。
文摘Cortical spreading depression (CSD) is a transient synaptic excitation, followed by depression, which can propagate slowly across cortex, subcortex and retina. CSD is implicated in migraine with aura and may lead to migraine pain. CSD can be suppressed by inhibition of both NR2A and NR2B containing N-methyl-D-aspartic acid (NMDA) receptors. However, whether there is a synergistic effect of co-inhibition of NR2A and NR2B containing receptors on CSD remains unknown. In this study, an efficient in vitro model of migraine with intrinsic optical imaging approach was applied to address this role of co-activation of both NR2A and NR2B in CSD. The results showed that co-application of NVP-AAM077, a drug selectively targeting for NR2A and Ro 25-6981, a drug selectively targeting for NR2B containing receptors, showed synergistic inhibitory effects on propagation rate and the magnitude of CSD in a concentration dependent manner in chick retina. Inhibition of CSD propagation was also observed by a clinical acceptable drug that antagonizes both NR2A and NR2B containing receptors, memantine, at 10 μM. These data suggest that combinational use of antagonists selectively targeting NR2A and NR2B containing receptors could be a useful strategy for preventative treatment of migraine with improved efficacy with potential alleviated side effects.
