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Ethyl pyruvate alleviates early brain injury following subarachnoid hemorrhage in rats

  • Experimental Research - Brain Injury
  • Published:
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Abstract

Background

Previous studies have demonstrated the neuroprotective effects of ethyl pyruvate in central nervous system (CNS) diseases. However, whether ethyl pyruvate attenuates early brain injury after subarachnoid hemorrhage (SAH) remains unknown. This study was conducted to investigate the potential effects of ethyl pyruvate on early brain injury induced by SAH and explore the underlying mechanisms.

Methods

Eighty-eight male Sprague-Dawley rats were used. An SAH model was induced by endovascular perforation. Ethyl pyruvate (100 mg/kg) or a vehicle was administered intraperitoneally at 1 h after SAH induction. SAH grade, neurological scores, brain water content, Evans blue extravasation, Western blots, and immunofluorescence were used to study the mechanisms of ethyl pyruvate.

Results

Ethyl pyruvate treatment inhibited microglia activation and reduced the expression of proinflammatory cytokines (IL-1β and TNF-α). Ethyl pyruvate treatment also prevented disruption of tight junction proteins (occluding and claudin-5) and reduced expression of MMP-9. In addition, ethyl pyruvate treatment markedly reduced TUNEL-positive cells and expression of cleaved caspase-3.

Conclusions

Our results indicated that ethyl pyruvate treatment attenuated early brain injury and improved neurological function after SAH by inhibiting microglia activation and apoptosis and stabilizing the BBB.

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Author information

Authors and Affiliations

  1. Department of Neurosurgery, The Affiliated Hospital of Hangzhou Normal University, Hangzhou, China

    Rong Fang & Mei Zhang

  2. Department of Geriatrics, The First Affiliated Hospital of Zhejiang University School of Medicine, Zhejiang, China

    Xiaojun Zheng

Authors
  1. Rong Fang
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  2. Xiaojun Zheng
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  3. Mei Zhang
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Corresponding author

Correspondence to Mei Zhang.

Ethics declarations

All experimental procedures for rats were approved by the Institutional Animal Care and Use Committee of Hangzhou Normal University and performed in accordance with the National Institutes of Health Guide for the Care and Use of Laboratory Animals

Conflict of interest

All authors certify that they have no affiliations with or involvement in any organization or entity with any financial interest or non-financial interest the subject matter or materials discussed in this manuscript.

Funding

No funding was received for this research.

Additional information

Comment

This study has the merit of focusing the research on aneurysmal subarachnoid hemorrhage (aSAH) on mechanisms of brain dysfunction that are different from cerebral vasospasm. Although cerebral vasospasm is still considered the principal cause of delayed neurological deterioration after aSAH, there is increasing scientific evidence that other pathogenetic mechanisms may play a role in determining delayed ischemia (1). Cerebral vasospasm and delayed ischemia could represent separate clinical entities both occurring in aSAH patients, but with different pathophysiologies and different relevance to the outcome. There are many hints confirming this hypothesis. Probably, the most evident is the fact that vasospasm is observed in most patients who suffer from aSAH, while only 20–30 % of them develop clinical symptoms. Another unequivocal piece of evidence showing that radiographic vasospasm and clinical outcome are not directly associated is the greater incidence of radiographic vasospasm in patients who undergo clipping as compared to those who receive endovascular treatment, but with similar results of the two techniques in terms of morbidity and mortality. These circumstances are widely recognized; nonetheless, they remain oddities that cannot be convincingly explained if we consider cerebral vasospasm as the only cause of delayed cerebral ischemia. Here the authors found that ethyl pyruvate alleviated behavioral dysfunction in experimental animals by inhibiting neural cell apoptosis and stabilizing the blood-brain barrier. These mechanisms, together with vasospasm, hypercoagulation, apoptosis, oxidative stress, cortical spreading depolarization, and inflammation, deserve further analysis concerning their role in the pathophysiology of neurological worsening after aSAH.

1. Tomasello F, Conti A (2015) The pathogenetic mechanism of delayed ischemic deficit in aneurysmal subarachnoid hemorrhage: a still-unsolved issue. World Neurosurg 84: 1207–1208.

Alfredo Conti

Messina, Italy

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Fang, R., Zheng, X. & Zhang, M. Ethyl pyruvate alleviates early brain injury following subarachnoid hemorrhage in rats. Acta Neurochir 158, 1069–1076 (2016). https://doi.org/10.1007/s00701-016-2795-3

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  • DOI: https://doi.org/10.1007/s00701-016-2795-3

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