联合细胞治疗和康复治疗后可改善行为，尽管中风大鼠长期存在小胶质细胞。

Additive Behavioral Improvement after Combined Cell Therapy and Rehabilitation Despite Long-Term Microglia Presence in Stroke Rats.

机构信息

Department of Neurology, University of Eastern Finland, FI-70210 Kuopio, Finland.

A. I. Virtanen Institute for Molecular Sciences, University of Eastern Finland, FI-70150 Kuopio, Finland.

出版信息

Int J Mol Sci. 2021 Feb 3;22(4):1512. doi: 10.3390/ijms22041512.

UNLABELLED

Microglia are involved in the post-stroke immunomodulation of brain plasticity, repair, and reorganization. Here, we evaluated whether adipose-tissue-derived mesenchymal stem cells (ADMSCs) and/or rehabilitation improve behavioral recovery by modulating long-term perilesional inflammation and creating a recovery-permissive environment in a rat model of ischemic stroke.

METHODS

A two-way mixed lymphocyte reaction was used to assess the immunomodulatory capacity of ADMSCs in vitro. Two or 7 days after permanent middle cerebral artery occlusion (pMCAO), rats were intravenously administered ADMSCs or vehicle and housed in a standard or enriched environment (EE). Behavioral performance was assessed with a cylinder test, then we performed stereological and ImageJ/Fiji quantifications of ionized calcium-binding adaptor molecule 1 (Iba1) cells and blood-brain barrier (BBB) leakage.

RESULTS

Human ADMSCs were immunosuppressive in vitro. The cylinder test showed partial spontaneous behavioral recovery of pMCAO rats, which was further improved by combined ADMSCs and housing in EE on days 21 and 42 ( < 0.05). We detected an ischemia-induced increase in numbers, staining intensity, and branch length of Iba1+ microglia/macrophages as well as BBB leakage in the perilesional cortex. However, these were not different among pMCAO groups.

CONCLUSION

Combined cell therapy and rehabilitation additively improved behavioral outcome despite long-term perilesional microglia presence in stroke rats.

未加标签

小胶质细胞参与脑可塑性、修复和重组的卒中后免疫调节。在这里，我们评估了脂肪组织来源的间充质干细胞（ADMSCs）和/或康复是否通过调节长期病变周围炎症和在缺血性卒中大鼠模型中创造恢复许可环境来改善行为恢复。

方法

使用双向混合淋巴细胞反应评估 ADMSCs 的体外免疫调节能力。在永久性大脑中动脉闭塞（pMCAO）后 2 天或 7 天，大鼠经静脉给予 ADMSCs 或载体，并在标准或丰富环境（EE）中饲养。使用圆筒试验评估行为表现，然后使用立体学和 ImageJ/Fiji 对离子钙结合衔接分子 1（Iba1）细胞和血脑屏障（BBB）渗漏进行定量。

结果

人 ADMSCs 在体外具有免疫抑制作用。圆筒试验显示 pMCAO 大鼠有部分自发行为恢复，在第 21 天和第 42 天联合 ADMSCs 和 EE 饲养时进一步改善（<0.05）。我们检测到缺血诱导的病变周围皮质中 Iba1+小胶质细胞/巨噬细胞数量、染色强度和分支长度以及 BBB 渗漏增加。然而，pMCAO 组之间没有差异。