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牙髓干细胞移植促进脑缺血性脑卒中后的神经元神经保护。

Dental pulp stem cell transplantation facilitates neuronal neuroprotection following cerebral ischemic stroke.

机构信息

Department of Neurosurgery, Renmin Hospital of Wuhan University, Wuhan, Hubei 430060, China.

Regenerative Medicine Lab, Tianyou Hospital, Wuhan University of Science and Technology, Wuhan, Hubei 430064, China.

出版信息

Biomed Pharmacother. 2022 Aug;152:113234. doi: 10.1016/j.biopha.2022.113234. Epub 2022 Jun 9.

Abstract

OBJECTIVES

This study aimed to identify and evaluate the intracranial transplantation of dental pulp stem cells (DPSCs) as a possible ischemic stroke therapy that mitigates neuronal death/apoptosis.

MATERIALS AND METHODS

DPSCs were isolated from the impacted third molars of healthy volunteers and then intracranially injected at 24 h post-ischemic stroke to Sprague Dawley rats that had been subjected to 2 h of middle cerebral artery occlusion. Neurological functional deficits were assessed using the modified neurological severity score (mNSS), and cerebral edema was quantified using brain water content. Neuronal death/apoptosis was indicated by TdT-mediated dUTP Nick-End Labeling (TUNEL) staining, NeuN immunofluorescence and immunohistochemistry, and Western blot analysis of the protein expression of anti-apoptotic indicator of Bcl-2 and apoptotic indicators of Bax and caspase 3.

RESULTS

DPSC transplantation could ameliorate neurological dysfunction and brain edema, reduce infarct volume, decrease the percentage of TUNEL-positive nuclei, increase the number and percentage of NeuN-positive cells in ischemic penumbra, increase the ratio of Bcl-2 and Bax and down-regulate the production of caspase 3 in the cortical infarct zone.

CONCLUSIONS

DPSC therapy via intracranial injection exerted remarkably neuroprotection mainly by inhibiting neuronal death/apoptosis.

摘要

目的

本研究旨在鉴定和评估牙髓干细胞(DPSCs)颅内移植作为减轻神经元死亡/凋亡的可能缺血性脑卒中治疗方法。

材料和方法

从健康志愿者的阻生第三磨牙中分离 DPSCs,然后在缺血性脑卒中后 24 小时内将其颅内注射到已接受 2 小时大脑中动脉闭塞的 Sprague Dawley 大鼠中。使用改良神经功能缺损评分(mNSS)评估神经功能缺损,并用脑水含量定量评估脑水肿。通过 TdT 介导的 dUTP 缺口末端标记(TUNEL)染色、NeuN 免疫荧光和免疫组织化学以及抗凋亡标志物 Bcl-2 和凋亡标志物 Bax 和 caspase 3 的蛋白表达的 Western blot 分析来指示神经元死亡/凋亡。

结果

DPSC 移植可改善神经功能障碍和脑水肿,减少梗死体积,减少 TUNEL 阳性核的百分比,增加缺血半影区中 NeuN 阳性细胞的数量和百分比,增加 Bcl-2 和 Bax 的比值,并下调皮质梗死区中 caspase 3 的产生。

结论

通过颅内注射的 DPSC 治疗主要通过抑制神经元死亡/凋亡发挥显著的神经保护作用。

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