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

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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.

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Data Availability

The data that support the findings of this study are available on request from the corresponding author. The data are not publicly available due to privacy or ethical restrictions.

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Acknowledgements

This article was a part of the thesis that was performed by Hamzeh Badeli Sarkala, PhD candidate in Anatomical Science.

Funding

This research was financed by grant number (94-01-01-10699) from the Shiraz University of Medical Sciences, Shiraz, Iran.

Author information

Authors and Affiliations

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

    Hamzeh Badeli Sarkala & Mohammad Reza Namavar

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

    Hamzeh Badeli Sarkala

  3. Neuroscience Research Center, Department of Anatomy, Faculty of Medicine, Golestan University of Medical Sciences, Gorgan, Iran

    Mehrdad Jahanshahi

  4. Department of Neuroscience, School of Advanced Medical Sciences and Technologies, Shiraz University of Medical Sciences, Shiraz, Iran

    Leila Kamali Dolatabadi

  5. Alzahra Research Institute, Isfahan University of Medical Sciences, Isfahan, Iran

    Leila Kamali Dolatabadi

  6. Histomorphometry and Stereology Research Center, Shiraz University of Medical Sciences, Shiraz, Iran

    Mohammad Reza Namavar

  7. Clinical Neurology Research Center, Shiraz University of Medical Sciences, Shiraz, Iran

    Mohammad Reza Namavar

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  1. Hamzeh Badeli Sarkala
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  2. Mehrdad Jahanshahi
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  3. Leila Kamali Dolatabadi
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Contributions

MRN designed and supervised the study, performed surgery, and edited the paper. HBS and LKD performed behavioral, histological, and stereological evaluations. HBS wrote the paper and prepared figures and graphs. MJ analyzed the data. All authors approved the final version of the paper.

Corresponding author

Correspondence to Mohammad Reza Namavar.

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All procedures were performed based on the National Institutes of Health’s Guidelines for Care and Use of Laboratory Animals and the Animal Research: Reporting in Vivo Experiments (ARRIVE) and approved by the local Ethical Committee of SUMS (SUMS.94-01-01-10699).

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Sarkala, H.B., Jahanshahi, M., Dolatabadi, L.K. et al. G-CSF improved the memory and dendritic morphology impairments in the hippocampal CA1 pyramidal neurons after brain ischemia in the male rats. Metab Brain Dis 38, 2573–2581 (2023). https://doi.org/10.1007/s11011-023-01286-4

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