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骨髓细胞在电惊厥小鼠中的抗惊厥活性。

Anticonvulsant activity of bone marrow cells in electroconvulsive seizures in mice.

机构信息

Laboratório de Neurofisiologia, Departamento de Fisiologia, Federal University of São Paulo - UNIFESP, R, Botucatu, 862 5 andar, V, Clementino - CEP, 04023-066, São Paulo, Brazil.

出版信息

BMC Neurosci. 2013 Sep 6;14:97. doi: 10.1186/1471-2202-14-97.

Abstract

BACKGROUND

Bone marrow is an accessible source of progenitor cells, which have been investigated as treatment for neurological diseases in a number of clinical trials. Here we evaluated the potential benefit of bone marrow cells in protecting against convulsive seizures induced by maximum electroconvulsive shock (MES), a widely used model for screening of anti-epileptic drugs. Behavioral and inflammatory responses were measured after MES induction in order to verify the effects promoted by transplantation of bone marrow cells. To assess the anticonvulsant effects of bone marrow cell transplantation, we measured the frequency and duration of tonic seizure, the mortality rate, the microglial expression and the blood levels of cytokine IL-1, IL-6, IL-10 and TNF-α after MES induction. We hypothesized that these behavioral and inflammatory responses to a strong stimulus such as a convulsive seizure could be modified by the transplantation of bone marrow cells.

RESULTS

Bone marrow transplanted cells altered the convulsive threshold and showed anticonvulsant effect by protecting from tonic seizures. Bone marrow cells modified the microglial expression in the analyzed brain areas, increased the IL-10 and attenuate IL-6 levels.

CONCLUSIONS

Bone marrow cells exert protective effects by blocking the course of electroconvulsive seizures. Additionally, electroconvulsive seizures induced acute inflammatory responses by altering the pattern of microglia expression, as well as in IL-6 and IL-10 levels. Our findings also indicated that the anticonvulsant effects of these cells can be tested with the MES model following the same paradigm used for drug testing in pharmacological screening. Studies on the inflammatory reaction in response to acute seizures in the presence of transplanted bone marrow cells might open a wide range of discussions on the mechanisms relevant to the pathophysiology of epilepsies.

摘要

背景

骨髓是祖细胞的可及来源,已在多项临床试验中被作为神经疾病治疗方法进行了研究。在此,我们评估了骨髓细胞在预防最大电休克(MES)诱导的惊厥性癫痫发作中的潜在益处,MES 是筛选抗癫痫药物的常用模型。进行 MES 诱导后,通过评估行为和炎症反应,验证了骨髓细胞移植的作用。为了评估骨髓细胞移植的抗惊厥作用,我们测量了强直发作的频率和持续时间、死亡率、小胶质细胞表达以及 MES 诱导后血液中细胞因子 IL-1、IL-6、IL-10 和 TNF-α 的水平。我们假设,骨髓细胞移植可改变对强刺激(如惊厥性癫痫发作)的行为和炎症反应。

结果

骨髓移植细胞改变了惊厥阈值,并通过防止强直发作发挥了抗惊厥作用。骨髓细胞改变了分析脑区的小胶质细胞表达,增加了 IL-10 并降低了 IL-6 水平。

结论

骨髓细胞通过阻断电休克惊厥的发生而发挥保护作用。此外,电休克惊厥通过改变小胶质细胞表达模式以及改变 IL-6 和 IL-10 水平,引发了急性炎症反应。我们的研究结果还表明,可以使用 MES 模型和药物筛选中使用的相同范式,测试这些细胞的抗惊厥作用。在存在移植骨髓细胞的情况下,对急性癫痫发作的炎症反应的研究可能会引发关于与癫痫病理生理学相关的机制的广泛讨论。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/2b58/3846761/bfe0650f210f/1471-2202-14-97-1.jpg

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