Department of Psychoneuroimmunology, University Medical Center Utrecht, Utrecht, The Netherlands.
Neurobiol Dis. 2010 May;38(2):266-72. doi: 10.1016/j.nbd.2010.01.016. Epub 2010 Feb 2.
We recently demonstrated that inhibition of the NF-kappaB-pathway by the specific peptide inhibitor TAT-NBD markedly reduced cerebral injury in a rat model of perinatal hypoxic-ischemic (HI) brain damage. The aim of the current study was to assess whether neuroprotection by TAT-NBD is associated with long-term functional improvements after neonatal HI. Postnatal-day 7 rats subjected to HI showed motor deficits in the cylinder rearing test and adhesive removal task. HI-treated animals also showed cognitive impairments in a visuo-spatial learning task (modified hole board) as defined by an increased latency to complete this task and increased numbers of short- and long-term memory errors. HI animals treated with TAT-NBD [20mg/kg i.p.] at 0 and 3h post-HI did not show impairments in the cylinder rearing test, adhesive removal task and modified hole board. In conclusion, the almost complete reduction in lesion size observed after TAT-NBD treatment was associated with long-lasting normalization of sensorimotor and cognitive functions.
我们最近的研究表明，通过特异性肽抑制剂 TAT-NBD 抑制 NF-κB 通路可以显著减轻新生大鼠缺氧缺血性脑损伤模型中的脑损伤。本研究的目的是评估 TAT-NBD 的神经保护作用是否与新生儿 HI 后的长期功能改善相关。生后 7 天的 HI 大鼠在圆筒站立试验和粘着物去除任务中表现出运动功能障碍。HI 处理的动物在视空间学习任务（改良孔板）中也表现出认知障碍，表现为完成该任务的潜伏期延长和短期和长期记忆错误增加。HI 动物在 HI 后 0 和 3 小时用 TAT-NBD [20mg/kg 腹腔内]处理后，在圆筒站立试验、粘着物去除试验和改良孔板中未出现损伤。总之，TAT-NBD 治疗后观察到的病变体积几乎完全减少与感觉运动和认知功能的长期正常化有关。
