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Adipose-Derived Stem Cell transplantation improves learning and memory via releasing neurotrophins in rat model of temporal lobe epilepsy.
Brain Research ( IF 2.7 ) Pub Date : 2020-09-11 , DOI: 10.1016/j.brainres.2020.147121
Lili Wang 1 , Yingchun Zhao 1 , Xiaochun Pan 1 , Yu Zhang 1 , Lin Lin 1 , Ying Wu 1 , Yanruo Huang 2 , Hua He 3
Affiliation  

Epilepsy is a common neurological disease and its most common type is temporal lobe epilepsy (TLE). Novel therapeutics is needed as many TLE patients are resistant to treatments like anticonvulsants or temporal lobectomy. Stem cell therapy has great promise in regeneration medicine. In the current study, we tried to investigate the potential protective effects of adipose-derived stem cell (ADSC) transplantation in epileptic rats. Epilepsy model was established by intra-hippocampal injection of kainic acid (KA) in rats. ADSCs were isolated, differentiated and transplanted into hippocampus of KA rats. There were three groups of rats: normal control group receiving saline injection and no transplantation, KA + sham group receiving KA injection and sham transplantation surgery and KA + transplantation group receiving KA injection and ADSC transplantation. We found that ADSCs were highly positive for CD44, CD90, CD29 and CD105, and neural differentiation induced the expression of neuronal markers like Tuj1, MAP2, NeuN and PSD-95. EEG recording showed that KA induced seizure activity while ADSC transplantation inhibited seizure activity. In training session of Morris water maze task, KA injection impaired the learning capacity of rats while ADSC transplantation restored the learning capacity at 2-week or 2-month post transplantation. In probe session of Morris water maze task, KA injection impaired the memory of rats while ADSC transplantation restored the memory at 2-week or 2-month post transplantation. Transplanted ADSCs released BDNF, NT3 and NT4. Pro-apoptotic BAX was reduced while anti-apoptotic BCL-2 and BCL-xL were increased in hippocampus post ADSC transplantation. Our study suggests that ADSC transplantation inhibits KA-induced seizures and improves the learning and memory function of epileptic rats.



中文翻译:

脂肪源性干细胞移植通过释放颞叶癫痫大鼠模型中的神经营养因子来改善学习和记忆。

癫痫是一种常见的神经系统疾病,最常见的类型是颞叶癫痫(TLE)。由于许多 TLE 患者对抗惊厥药或颞叶切除术等治疗有抵抗力,因此需要新的治疗方法。干细胞疗法在再生医学领域有着广阔的前景。在目前的研究中,我们试图研究脂肪干细胞 (ADSC) 移植对癫痫大鼠的潜在保护作用。大鼠海马内注射红藻氨酸(KA)建立癫痫模型。ADSCs被分离、分化并移植到KA大鼠的海马中。3组大鼠:正常对照组注射生理盐水不移植,KA+sham组接受KA注射和假移植手术,KA+移植组接受KA注射和ADSC移植。我们发现 ADSC 对 CD44、CD90、CD29 和 CD105 呈高度阳性,并且神经分化诱导了神经元标记物(如 Tuj1、MAP2、NeuN 和 PSD-95)的表达。脑电图记录显示 KA 诱导癫痫发作,而 ADSC 移植抑制癫痫发作。在Morris水迷宫任务训练中,KA注射损害大鼠的学习能力,而ADSC移植在移植后2周或2个月恢复学习能力。在Morris水迷宫任务的探查阶段,KA注射损害大鼠的记忆,而ADSC移植在移植后2周或2个月恢复记忆。移植的 ADSC 释放 BDNF、NT3 和 NT4。ADSC 移植后海马中促凋亡 BAX 减少,而抗凋亡 BCL-2 和 BCL-xL 增加。我们的研究表明,ADSC 移植可抑制 KA 诱发的癫痫发作并改善癫痫大鼠的学习和记忆功能。

更新日期:2020-10-30
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