Exosomes Treatment Mitigates Ischemic Brain Damage but Does Not Improve Post-Stroke Neurological Outcome.

Exosomes Treatment Mitigates Ischemic Brain Damage but Does Not Improve Post-Stroke Neurological Outcome.
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DOI:
10.33594/000000090
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发表时间:
2019-01-01
期刊:
Cellular physiology and biochemistry : international journal of experimental cellular physiology, biochemistry, and pharmacology
影响因子:
--
通讯作者:
Veeravalli, Krishna Kumar
Veeravalli, Krishna Kumar
中科院分区:
其他
文献类型:
--
作者:
Nalamolu, Koteswara Rao;Venkatesh, Ishwarya;Veeravalli, Krishna Kumar

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背景/目的:最近的研究表明,从人脐带血中获得的间充质干细胞(MSC)的治疗提高了存活率,减少了脑损伤,防止细胞凋亡,抑制炎症反应,下调DNA损伤诱导基因,上调DNA修复基因,并促进脑卒中诱导动物的神经恢复。新兴的中风文献支持这样的概念,即从MSC释放的外泌体是MSC治疗提供的中风后神经保护的主要生物学原理。因为用外来体治疗具有克服与基于细胞的疗法相关的局限性的巨大潜力,我们测试了在标准培养条件下从HUCB-MSC分泌的外泌体对后通过在缺血前和再灌注前定期进行TTC染色以及改良的神经学严重性评分、改良的粘合剂去除、梁行走和加速旋转棒性能测试,在缺血性中风大鼠模型中观察中风脑损伤和神经学结果。外泌体治疗减小了梗死面积。治疗与外泌体并没有影响中风后的生存率和体重的变化,但加剧了躯体感觉和运动功能障碍,并产生不利影响的自然恢复,发生没有任何treatment.CONCLUSION:治疗与外泌体分泌的HUCB-MSCs在标准培养条件下减弱缺血性脑损伤,但并没有改善中风后的神经功能的结果。
BACKGROUND/AIMS: Recent studies demonstrated that the treatment with mesenchymal stem cells (MSCs) obtained from the human umbilical cord blood improved survival, reduced brain damage, prevented apoptosis, suppressed inflammatory responses, downregulated the DNA damage-inducing genes, upregulated the DNA repair genes, and facilitated neurological recovery in stroke-induced animals. Emerging stroke literature supports the concept that the exosomes released from MSCs are the primary biological principles underlying the post-stroke neuroprotection offered by MSCs treatment.METHODS: Because the treatment with exosomes has a great potential to overcome the limitations associated with cell-based therapies, we tested the efficacy of exosomes secreted from HUCB-MSCs under standard culture conditions on post-stroke brain damage and neurological outcome in a rat model of ischemic stroke by performing TTC staining as well as the modified neurological severity scores, modified adhesive removal, beam-walking, and accelerating Rotarod performance tests before ischemia and at regular intervals until seven days reperfusion.RESULTS: Exosomes treatment attenuated the infarct size. Treatment with exosomes did not affect the post-stroke survival rate and body weight changes, but exacerbated the somatosensory and motor dysfunction and adversely affected the natural recovery that occurs without any treatment.CONCLUSION: Treatment with exosomes secreted from HUCB-MSCs under standard culture conditions attenuates the ischemic brain damage but does not improve the post-stroke neurological outcome.