Potential effect of endothelial progenitor cells on pentylenetetrazole-induced seizures in rats: an evaluation of relevant lncRNAs

Shimaa O. ALI; Nancy N. SHAHIN; Marwa M. SAFAR; Sherine M. RIZK

doi:10.1631/jzus.B2400242

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Potential effect of endothelial progenitor cells on pentylenetetrazole-induced seizures in rats: an evaluation of relevant lncRNAs

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Research Article | Updated：2025-08-25

Potential effect of endothelial progenitor cells on pentylenetetrazole-induced seizures in rats: an evaluation of relevant lncRNAs
Potential effect of endothelial progenitor cells on pentylenetetrazole-induced seizures in rats: an evaluation of relevant lncRNAs
内皮祖细胞对戊四氮致痫大鼠的潜在影响：通过相关lncRNAs进行评估
Journal of Zhejiang University-SCIENCE B (Biomedicine & Biotechnology) Vol. 26, Issue 8, Pages: 789-804(2025)
Affiliations：

1.Biochemistry Department, Faculty of Pharmacy, Cairo University, Cairo 11562, Egypt
2.Pharmacology and Toxicology Department, Faculty of Pharmacy, Cairo University, Cairo 11562, Egypt
3.Pharmacology and Biochemistry Department, Faculty of Pharmacy, The British University in Egypt, Cairo 11837, Egypt
Funds：
DOI：10.1631/jzus.B2400242
CLC：
CSTR：
Received：10 May 2024，

Revised：20 September 2024，

Published：25 August 2025
Accepted：

Shimaa O. ALI,Nancy N. SHAHIN,Marwa M. SAFAR等.内皮祖细胞对戊四氮致痫大鼠的潜在影响：通过相关lncRNAs进行评估[J].浙江大学学报（英文版）（B辑：生物医学和生物技术）,2025,26(08):789-804.

Shimaa O. ALI, Nancy N. SHAHIN, Marwa M. SAFAR, et al. Potential effect of endothelial progenitor cells on pentylenetetrazole-induced seizures in rats: an evaluation of relevant lncRNAs[J]. Journal of zhejiang university-science b (biomedicine & biotechnology), 2025, 26(8): 789-804.
Shimaa O. ALI,Nancy N. SHAHIN,Marwa M. SAFAR等.内皮祖细胞对戊四氮致痫大鼠的潜在影响：通过相关lncRNAs进行评估[J].浙江大学学报（英文版）（B辑：生物医学和生物技术）,2025,26(08):789-804. DOI： 10.1631/jzus.B2400242.

Shimaa O. ALI, Nancy N. SHAHIN, Marwa M. SAFAR, et al. Potential effect of endothelial progenitor cells on pentylenetetrazole-induced seizures in rats: an evaluation of relevant lncRNAs[J]. Journal of zhejiang university-science b (biomedicine & biotechnology), 2025, 26(8): 789-804. DOI： 10.1631/jzus.B2400242.

摘要

干细胞因其独特的特性，在癫痫治疗中展现出广阔的应用前景。本研究探讨了内皮祖细胞（EPCs）在戊四氮（PTZ）诱导的大鼠癫痫模型中的作用，并分析了一组在脑神经调控网络和自噬通路中起着维持精细平衡作用的长链非编码RNAs（lncRNAs）。通过检测神经损伤标志物、神经营养因子和相关lncRNA基因的表达，评估了静脉注射EPCs对PTZ致痫大鼠的影响，并采用Y迷宫测试和旷场实验（OFT）对大鼠的行为进行评估。研究结果显示，EPCs能减轻癫痫发作相关的神经损伤，并逆转PTZ诱导的工作记忆和运动活动障碍，这可从Y迷宫和OFT测试中表现改善得到了印证。EPCs治疗逆转了lncRNAs

Evf2

、

Pnky

、

Dlx1

、

APF

、

HOTAIR

和

FLJ11812

的下调，同时促进了血管内皮生长因子（VEGF）的表达，其改善作用与丙戊酸相当。综上，EPCs可改善点燃型癫痫发作及其相关异常，该作用可能通过上调特定调控性lncRNAs介导。

Abstract

Objective

The use of stem cells is a promising strategy for seizure treatment owing to their unique characteristics. We investigated the role of endothelial progenitor cells (EPCs) in a pentylenetetrazole (PTZ)‍-induced rat seizure model. A selected panel of long noncoding RNAs (lncRNAs)

which maintain an elaborate balance in brain neural regulatory networks as well as the autophagy pathway

was also targeted.

Methods

The impact of intravenously administered EPCs on PTZ-induced kindling in rats was evaluated by measuring the expression of neuronal damage markers

neurotrophic factors

and relevant lncRNA genes. Rat behavior was assessed using Y-maze test and open field test (OFT).

Results

EPCs mitigated seizure-associated neurological damage and reversed PTZ-induced working memory and locomotor activity deficits

as evidenced by improved performance in the Y-maze test and OFT. EPC treatment reversed the downregulation of the expression of the lncRNAs

Evf2

Pnky

Dlx1

APF

HOTAIR

and

FLJ11812

. EPCs also boosted vascular endothelial growth factor (VEGF) expression. The ameliorative effect achieved by EPCs was comparable to that produced by valproate.

Conclusions

These findings indicate that EPCs ameliorate kindling epileptic seizures and their associated abnormalities and that the effect of EPCs may be mediated via the upregulation of certain regulatory lncRNAs.

关键词

Keywords

references

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