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Neuroprotective effects of neurotropin in a mouse model of hypoxic–ischemic brain injury

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Abstract

Purpose

Ischemic–hypoxic insult leads to detrimental effects on multiple organs. The brain is especially vulnerable, and it is hard to regenerate once damaged. Currently, therapeutic options are very limited. Previous studies have reported neuroprotective effects of neurotropin, a non-protein extract derived from the inflamed skin of rabbits inoculated with vaccinia virus, using a murine model of peripheral nerve injury and cultured cell lines. However, whether neurotropin might have protective effects against brain injuries remains unclear. We, therefore, investigated the neuroprotective effect of neurotropin and possible underlying mechanisms, using a mouse model of hypoxic–ischemic brain injury.

Methods

Hypoxic–ischemic brain injury was induced via a combination of the left common carotid artery occlusion and exposure to hypoxic environment (8% oxygen) in adult male C57BL/6 mice. Immediately following induction of hypoxia–ischemia, mice received either saline or 2.4 units of neurotropin. The survival rate, neurological function, infarct volume, and expression of inflammatory cytokines were evaluated.

Results

Compared to the control group, the neurotropin group exhibited a significantly higher survival rate (100% vs. 62.5%, p < 0.05) and lower neurological deficit scores (1; 0–2 vs. 3; 0–5, median; range, p < 0.05) after the hypoxic–ischemic insult. The administration of neurotropin also reduced infarct volume (18.3 ± 5.1% vs. 38.3 ± 7.2%, p < 0.05) and mRNA expression of pro-inflammatory cytokines.

Conclusions

The post-treatment with neurotropin improved survival and neurological outcomes after hypoxic–ischemic insult. Our results indicate that neurotropin has neuroprotective effects against hypoxic–ischemic brain injury by suppressing pro-inflammatory cytokines.

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Funding

This work was supported by the Japan Society for Promotion of Science (JSPS KAKENHI Grant number 15K10507 and 17K11044).

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Authors and Affiliations

  1. Department of Anesthesiology, Faculty of Medicine, University of Yamanashi, 1110 Shimokato, Chuo, Yamanashi, 4093898, Japan

    Sohei Hishiyama, Masakazu Kotoda & Takashi Matsukawa

  2. Surgical Center, University of Yamanashi Hospital, University of Yamanashi, Chuo, Yamanashi, Japan

    Tadahiko Ishiyama & Kazuha Mitsui

Authors
  1. Sohei Hishiyama
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  2. Masakazu Kotoda
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  3. Tadahiko Ishiyama
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  4. Kazuha Mitsui
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  5. Takashi Matsukawa
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Correspondence to Masakazu Kotoda.

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Hishiyama, S., Kotoda, M., Ishiyama, T. et al. Neuroprotective effects of neurotropin in a mouse model of hypoxic–ischemic brain injury. J Anesth 33, 495–500 (2019). https://doi.org/10.1007/s00540-019-02655-z

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  • DOI: https://doi.org/10.1007/s00540-019-02655-z

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