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Valproic Acid Pretreatment Reduces Brain Edema in a Rat Model of Surgical Brain Injury

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Brain Edema XVI

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

Abstract

Surgically induced brain injury (SBI) results in brain edema and neurological decline. Valproic acid (VA) has been shown to be neuroprotective in several experimental brain diseases. In this study, we investigated the pretreatment effect of VA in a rat model of SBI. A total of 57 male Sprague-Dawley rats were use in four groups: sham, SBI + vehicle, SBI + low dose (100 mg/kg) VA, and SBI + high dose (300 mg/kg) VA. SBI was induced by partially resecting right frontal lobes. Shams underwent identical surgical procedures without brain resection. VA or vehicle was administered subcutaneously 30 min prior to SBI. At 24 and 72 h post SBI, neurobehavior and brain water content were assessed as well as matrix metalloproteinases (MMPs) activities. There was significantly higher brain water content within the right frontal lobe in SBI rats than in shams. Without neurobehavioral improvements, the low-dose but not high-dose VA significantly reduced brain edema at 24 h post SBI. The protection tends to persist to 72 h post SBI. At 24 h post SBI, low-dose VA did not significantly reduce the elevated MMP-9 activity associated with SBI. In conclusion, VA pretreatment attenuated brain edema at 24 h after SBI but lacked MMP inhibition. The single dose VA was not associated with neurobehavioral benefits.

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Acknowledgments

This study is partially supported by grants from National Institute of Health (NIH) NS081740, NS043338 to J. Zhang.

Conflict of Interest Statement

All authors have no conflicts of interest to disclose.

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Authors and Affiliations

  1. Department of Anesthesiology, Loma Linda University, Room 2532 LLUMC, 11234 Anderson Street, Loma Linda, CA, 92374, USA

    Lei Huang, Nikan H. Khatibi, Richard L. Applegate II MD, Robert D. Martin & John Zhang

  2. Division of Physiology, Department of Basic Science, Loma Linda University, Loma Linda, CA, USA

    Lei Huang, Wendy Woo, Prativa Sherchan, Paul Krafft, William Rolland & John Zhang

  3. Department of Neurosurgery, Loma Linda University, Loma Linda, CA, USA

    John Zhang

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  1. Lei Huang
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  2. Wendy Woo
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  3. Prativa Sherchan
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  4. Nikan H. Khatibi
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  5. Paul Krafft
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  6. William Rolland
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  7. Richard L. Applegate II MD
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  8. Robert D. Martin
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  9. John Zhang
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Corresponding author

Correspondence to Richard L. Applegate II MD .

Editor information

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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Huang, L. et al. (2016). Valproic Acid Pretreatment Reduces Brain Edema in a Rat Model of Surgical Brain 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_53

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  • DOI: https://doi.org/10.1007/978-3-319-18497-5_53

  • 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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