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Brain Edema XVI pp 379–384Cite as

Effects of Aerobic Capacity on Thrombin-Induced Hydrocephalus and White Matter Injury

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Part of the book series: Acta Neurochirurgica Supplement ((NEUROCHIRURGICA,volume 121))

Abstract

We have previously shown that intracerebral hemorrhage-induced brain injury is less in rats bred for high aerobic capacity (high capacity runners; HCR) compared with those bred for low aerobic capacity (low capacity runners; LCRs). Thrombin, an essential component in the coagulation cascade, is produced after cerebral hemorrhage. Intraventricular injection of thrombin causes significant hydrocephalus and white matter damage. In the present study, we examined the effect of exercise capacity on thrombin-induced hydrocephalus and white matter damage. Mid-aged (13-month-old) female LCRs (n = 13) and HCRs (n = 12) rats were used in this study. Rats received an intraventricular injection of thrombin (3 U, 50 μl). All rats underwent magnetic resonance imaging (MRI) at 24 h and were then euthanized for brain histology and Western blot. The mortalities were 20 % in LCRs and 33 % in HCRs after thrombin injection (p > 0.05). No rats died after saline injection. Intraventricular thrombin injection resulted in hydrocephalus and periventricular white matter damage as determined on MRI. In LCR rats, thrombin induced significant ventricle enlargement (23.0 ± 2.3 vs12.8 ± 1.9 mm3 in LCR saline group; p < 0.01) and white matter lesion (9.3 ± 7.6 vs 0.6 ± 0.5 mm3 in LCR saline group, p < 0.05). In comparison, in HCR rats thrombin induced less ventricular enlargement (17.3 ± 3.9 vs 23.0 ± 2.3 mm3 in LCRs, p < 0.01) and smaller white matter lesions (2.6 ± 1.2 mm3 vs 9.3 ± 7.6 mm3 in LCRs, p < 0.05). In LCR rats, there was also upregulation of heat shock protein-32, a stress marker, and microglial activation in the periventricular white matter. These changes were significantly reduced in HCR rats. Intraventricular injection of thrombin caused more white matter damage and hydrocephalus in rats with low aerobic capacity. A differential effect of thrombin may contribute to differences in the effects of cerebral hemorrhage with aerobic capacity.

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Acknowledgments

This study was supported by grants NS-073959, NS079157, and NS-084049 from the National Institutes of Health (NIH) and 973 Program-2014CB541600. The LCR-HCR rat model system was funded by the Office of Research Infrastructure Programs/OD grant R24OD010950 and by grant R01DK099034 (to LGK and SLB) from the National Institutes of Health. SLB was also supported by National Institutes of Health grants R01DK077200 and R01GM104194. We acknowledge the expert care of the rat colony provided by Molly Kalahar and Lori Heckenkamp. Contact LGK (lgkoch@med.umich.edu) or SLB (brittons@umich.edu) for information on the LCR and HCR rats: these rat models are maintained as an international resource with support from the Department of Anesthesiology at the University of Michigan, Ann Arbor, Michigan.

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Authors and Affiliations

  1. Department of Neurosurgery, University of Michigan, R5018 Biomedical Science Research Building, 109 Zina Pitcher Place, Ann Arbor, MI, 48109-2200, USA

    Wei Ni, Feng Gao, Mingzhe Zheng, Richard F. Keep PhD, Guohua Xi MD & Ya Hua MD

  2. Department of Neurosurgery, Huashan Hospital, Fudan University, Shanghai, China

    Wei Ni & Mingzhe Zheng

  3. Department of Neurology, the 2nd Affiliate Hospital, Zhejiang University, Zhejiang, China

    Feng Gao

  4. Department of Anesthesiology, University of Michigan, Ann Arbor, MI, USA

    Lauren G. Koch & Steven L. Britton

Authors
  1. Wei Ni
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  2. Feng Gao
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  3. Mingzhe Zheng
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  4. Lauren G. Koch
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  5. Steven L. Britton
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  6. Richard F. Keep PhD
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  7. Guohua Xi MD
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  8. Ya Hua MD
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Corresponding author

Correspondence to Ya Hua MD .

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Editors and Affiliations

  1. Department of Anesthesiology, Loma Linda University School of Medicine, Loma Linda, California, USA

    Richard L. Applegate

  2. Department of Neurosurgery, Soochow University The First Affiliated Hospital, Suzhou, Jiangsu, China

    Gang Chen

  3. Department of Neurosurgery, Third Military Medical University Southwest Hospital, Chongqing, China

    Hua Feng

  4. Dept.of Anesthesiology, Physiology and Neurosurgery, Loma Linda University School of Medicine, Loma Linda, California, USA

    John H. Zhang

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© 2016 Springer International Publishing Switzerland

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Ni, W. et al. (2016). Effects of Aerobic Capacity on Thrombin-Induced Hydrocephalus and White Matter Injury. In: Applegate, R., Chen, G., Feng, H., Zhang, J. (eds) Brain Edema XVI. Acta Neurochirurgica Supplement, vol 121. Springer, Cham. https://doi.org/10.1007/978-3-319-18497-5_65

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  • DOI: https://doi.org/10.1007/978-3-319-18497-5_65

  • Publisher Name: Springer, Cham

  • Print ISBN: 978-3-319-18496-8

  • Online ISBN: 978-3-319-18497-5

  • eBook Packages: MedicineMedicine (R0)

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