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G-CSF 改善了雄性大鼠脑缺血后海马 CA1 锥体神经元的记忆和树突形态损伤。

G-CSF improved the memory and dendritic morphology impairments in the hippocampal CA1 pyramidal neurons after brain ischemia in the male rats.

机构信息

Department of Anatomical Sciences, School of Medicine, Shiraz University of Medical Sciences, Shiraz, Iran.

Department of Anatomy, School of Medicine, Iran University of Medical Sciences, Tehran, Iran.

出版信息

Metab Brain Dis. 2023 Dec;38(8):2573-2581. doi: 10.1007/s11011-023-01286-4. Epub 2023 Sep 20.

DOI:10.1007/s11011-023-01286-4
PMID:37728699
Abstract

BACKGROUND

Stroke remains the leading cause of death and disability in the world. A new potential treatment for stroke is the granulocyte colony-stimulating factor (G-CSF), which exerts neuroprotective effects through multiple mechanisms. Memory impairment is the most common cognitive problem after a stroke. The suggested treatment for memory impairments is cognitive rehabilitation, which is often ineffective. The hippocampus plays an important role in memory formation. This project aimed to study the effect of G-CSF on memory and dendritic morphology of hippocampal CA1 pyramidal neurons after middle cerebral artery occlusion (MCAO)in rats.

METHODS

Male Sprague-Dawley rats were divided into three groups: the sham, control (MCAO + Vehicle), and treatment (MCAO + G-CSF) groups. G-CSF (50 µg/kg S.C) was administered at 6, 24, and 48 h after brain ischemia induction. The passive avoidance task to evaluate learning and memory was performed on days 6 and 7 post-ischemia. Seven days after MCAO, the brain was removed and the hippocampal slices were stained with Golgi. After that, the neurons were analyzed for dendritic morphology and maturity.

OUTCOMES

The data showed that stroke was associated with a significant impairment in the acquisition and retention of passive avoidance tasks, while the G-CSF improved learning and memory loss. The dendritic length, arborization, spine density, and mature spines of the hippocampus CA1 neurons were significantly reduced in the control group, and treatment with G-CSF significantly increased these parameters.

CONCLUSION

G-CSF, even with three doses, improved learning and memory deficits, and dendritic morphological changes in the CA1 hippocampal neurons resulted from brain ischemia.

摘要

背景

中风仍然是世界上导致死亡和残疾的主要原因。一种新的中风潜在治疗方法是粒细胞集落刺激因子(G-CSF),它通过多种机制发挥神经保护作用。记忆障碍是中风后最常见的认知问题。建议使用认知康复治疗记忆障碍,但往往效果不佳。海马体在记忆形成中起着重要作用。本项目旨在研究 G-CSF 对大脑中动脉闭塞(MCAO)后大鼠海马 CA1 锥体神经元记忆和树突形态的影响。

方法

雄性 Sprague-Dawley 大鼠分为三组:假手术组、对照组(MCAO+Vehicle)和治疗组(MCAO+G-CSF)。脑缺血诱导后 6、24 和 48 小时给予 G-CSF(50μg/kg S.C)。缺血后第 6 和第 7 天进行被动回避任务以评估学习和记忆。MCAO 后 7 天取出大脑,用 Golg 染色海马切片。之后,分析神经元的树突形态和成熟度。

结果

数据显示,中风与被动回避任务的获得和保留明显受损有关,而 G-CSF 可改善学习和记忆丧失。对照组海马 CA1 神经元的树突长度、分支、棘密度和成熟棘明显减少,而 G-CSF 治疗显著增加了这些参数。

结论

即使给予三剂 G-CSF,也能改善学习和记忆缺陷,并改善脑缺血引起的 CA1 海马神经元的树突形态变化。

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