Alizamir Tahereh, Jouzdani Ali Fathi, Attari Fatemeh, Arab Leila, Ashaari Zeinab, Komaki Alireza, Hassanzadeh Gholamreza
Department of Anatomy, School of Medicine, Hamadan University of Medical Sciences, Hamadan, Iran.
Neurophysiology Research Center, Hamadan University of Medical Sciences, Hamadan, Iran.
IBRO Neurosci Rep. 2025 Apr 28;18:759-770. doi: 10.1016/j.ibneur.2025.04.015. eCollection 2025 Jun.
MicroRNAs (miRNAs) play crucial roles in regulating cell survival and signaling pathways. Mesenchymal stem cells (MSCs), particularly those derived from Wharton's Jelly (WJ-MSCs), have shown potential in promoting cell survival and reducing apoptosis. This study evaluates the effects of WJ-MSCs on miRNA expression and apoptosis markers in an ischemic brain injury model.
Male Wistar rats (n = 30) were divided into control, sham, WJ-MSCs, Middle Cerebral Artery Occlusion (MCAO), and MCAO+WJ-MSCs groups. After 60 minutes of ischemia and 24 hours of reperfusion, WJ-MSCs were administered intracerebroventricularly. Post-surgical brain samples were analyzed using immunohistochemistry, TUNEL assay, and qRT-PCR to measure Bax/Bcl-2 ratios and miRNA (miR-497, miR-134, miR-181) expression in the cortex.
Immunohistochemistry revealed that the Bax/Bcl-2 ratio was significantly increased in the MCAO group, reflecting a pro-apoptotic state. In contrast, WJ-MSC treatment significantly reduced the Bax/Bcl-2 ratio in the ischemic cortex, suggesting a shift towards anti-apoptotic activity. Additionally, analysis of miRNA expression showed significantly elevated levels of miR-497, miR-134, and miR-181 in the brains of ischemic rats, which were associated with increased neuronal cell death. WJ-MSC treatment effectively modulated these miRNAs, resulting in a marked reduction in their expression. Furthermore, the TUNEL assay confirmed a substantial reduction in the number of apoptotic cells in the MCAO+WJ-MSCs group compared to the MCAO group. In the cortex, apoptotic cells were observed in WJ-MSC-treated rats, indicating enhanced neuronal survival.
WJ-MSCs mitigate ischemic brain injury by modulating miRNA expression and apoptotic markers, promoting neuronal survival. These findings highlight their potential as a therapeutic strategy for ischemic brain injuries.
微小RNA（miRNA）在调节细胞存活和信号通路中发挥着关键作用。间充质干细胞（MSC），尤其是源自脐带华通氏胶的间充质干细胞（WJ-MSC），已显示出促进细胞存活和减少细胞凋亡的潜力。本研究评估了WJ-MSC对缺血性脑损伤模型中miRNA表达和凋亡标志物的影响。
将雄性Wistar大鼠（n = 30）分为对照组、假手术组、WJ-MSC组、大脑中动脉闭塞（MCAO）组和MCAO+WJ-MSC组。缺血60分钟和再灌注24小时后，经脑室内给予WJ-MSC。术后对脑样本进行免疫组织化学、TUNEL检测和qRT-PCR分析，以测量皮质中Bax/Bcl-2比值和miRNA（miR-497、miR-134、miR-181）的表达。
免疫组织化学显示，MCAO组的Bax/Bcl-2比值显著升高，反映出促凋亡状态。相比之下，WJ-MSC治疗显著降低了缺血皮质中的Bax/Bcl-2比值，表明向抗凋亡活性转变。此外，miRNA表达分析显示，缺血大鼠脑中miR-497、miR-134和miR-181的水平显著升高，这与神经元细胞死亡增加有关。WJ-MSC治疗有效地调节了这些miRNA，导致其表达显著降低。此外，TUNEL检测证实，与MCAO组相比，MCAO+WJ-MSC组的凋亡细胞数量大幅减少。在皮质中，在接受WJ-MSC治疗的大鼠中观察到凋亡细胞，表明神经元存活率提高。
WJ-MSC通过调节miRNA表达和凋亡标志物减轻缺血性脑损伤，促进神经元存活。这些发现突出了它们作为缺血性脑损伤治疗策略的潜力。
