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Concurrent use of granulocyte-colony stimulating factor with repetitive transcranial magnetic stimulation did not enhance recovery of function in the early subacute stroke in rats

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Abstract

We investigated the additive effect of repetitive transcranial magnetic stimulation (rTMS) combined with granulocyte-colony stimulating factor (G-CSF) on functional outcome in the early subacute phase of stroke. Seven-week-old male rats were subjected to permanent middle cerebral artery occlusion (MCAo) and were divided into four groups: normal saline administration with sham rTMS (group 1, n = 15), G-CSF administration with sham rTMS (group 2, n = 15), G-CSF with 1 Hz rTMS (group 3, n = 14), and G-CSF with 20 Hz rTMS (group 4, n = 15). Animals received G-CSF or saline for 5 days from the day of MCAo and were concurrently treated with 20-min rTMS on their lesioned hemisphere for 2 weeks. Neurological functional score was worse in group 4 compared to that in group 2 on day 15. In Western blots conducted on day 25, phosphorylation of endothelial nitric oxide synthase was markedly lower in groups 2, 3, and 4 than that in group 1 in the ischemic border zone. PECAM-1 expression at ischemic core was lower in groups 4 than in group 2. Caspase-3 expression was markedly higher in groups 4 than in group 1, 2, 3 at ischemic core. Iba1 expression was higher in groups 4 than in group 1, 2 at ischemic core. G-CSF combined with rTMS administered in the early subacute phase of ischemic stroke may exert a hazardous effect on functional recovery, possibly due to impaired angiogenic mechanism, decreased cell survival, and increased inflammation.

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Acknowledgments

The authors would like to thank Jin-Joo Lee for technical assistance.

Conflict of interest

This work was supported by grant from the Korean Stroke Society young investigator’s award (KSS-2009-002) and Seoul National University Hospital (09-2009-0020).

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Authors and Affiliations

  1. Department of Rehabilitation Medicine, Chungnam National University Hospital, Daejeon, 301-721, Republic of Korea

    Jaewon Beom

  2. Department of Biomedical Engineering, Seoul National University College of Medicine, Seoul, 110-744, Republic of Korea

    Jaewon Beom

  3. Department of Rehabilitation Medicine, Asan Medical Center, Seoul, 138-736, Republic of Korea

    Won Kim

  4. Department of Rehabilitation Medicine, Seoul National University Hospital, Seoul National University College of Medicine, 101 Daehak-ro, Jongno-gu, Seoul, 110-744, Republic of Korea

    Tai Ryoon Han, Kwan-Sik Seo & Byung-Mo Oh

  5. Department of Rehabilitation Medicine, Gangwon Do Rehabilitation Hospital, Chuncheon-si, Gangwon-do, 200-939, Republic of Korea

    Tai Ryoon Han

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  1. Jaewon Beom
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Correspondence to Byung-Mo Oh.

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Beom, J., Kim, W., Han, T.R. et al. Concurrent use of granulocyte-colony stimulating factor with repetitive transcranial magnetic stimulation did not enhance recovery of function in the early subacute stroke in rats. Neurol Sci 36, 771–777 (2015). https://doi.org/10.1007/s10072-014-2046-4

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  • DOI: https://doi.org/10.1007/s10072-014-2046-4

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