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Systemic Administration of LPS Worsens Delayed Deterioration Associated with Vasospasm After Subarachnoid Hemorrhage Through a Myeloid Cell-Dependent Mechanism

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Abstract

Background

Delayed deterioration associated with vasospasm (DDAV) after aneurismal subarachnoid hemorrhage (SAH) is a major cause of morbidity. We have previously shown that myeloid cell depletion before experimental SAH in a murine model ameliorates DDAV. In this study, we address whether systemic administration of lipopolysaccharide (LPS) worsens DDAV in a myeloid cell-dependent fashion.

Methods

We challenged mice in our experimental SAH model with LPS before hemorrhage and evaluated the degree of vasospasm on day 6 with India ink angiography; behavioral deficits by rotorod, Y-maze, and Barnes maze testing; microglial activation early after SAH by immunohistochemistry; and the brain levels of the chemokines CCL5 and KC at the time of vasospasm. Another group of animals were given the myeloid cell-depleting antibody against the neutrophil antigen Ly6G/C prior to LPS administration and SAH.

Results

LPS followed by SAH significantly worsens angiographic vasospasm as well as performance on the Barnes maze but not the Y-maze or rotorod tests. There was an increased activation of microglia in animals with LPS before SAH compared to SAH alone. Depletion of myeloid cells before LPS administration inhibited the development of vasospasm, improved the performance on behavioral tests, and reduced microglial activation. The chemokines CCL5 and KC were incrementally elevated in SAH and LPS SAH, but suppressed in animals with myeloid cell depletion.

Conclusions

LPS administration before SAH worsens DDAV through a myeloid cell-dependent mechanism supporting studies in humans which show that systemic inflammation increases the likelihood of developing DDAV.

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Acknowledgments

The authors would like to thank James Bena for the statistical assistance. This work was supported by a grant from the NIH (K08-NS051350 JJP) and the Cleveland Clinic Cerebrovascular Center (Institutional Support JJP).

Conflict of interest

The authors declared that they have no conflicts of interest.

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Authors and Affiliations

  1. Cerebrovascular Center, Cleveland Clinic, NC30, 9500 Euclid Ave., Cleveland, OH, 44195, USA

    Saksith Smithason & J. Javier Provencio

  2. Neuroinflammation Research Center, Cleveland Clinic, NC30, 9500 Euclid Ave., Cleveland, OH, 44195, USA

    Saksith Smithason, Shari Korday Moore & J. Javier Provencio

Authors
  1. Saksith Smithason
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  2. Shari Korday Moore
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  3. J. Javier Provencio
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Correspondence to J. Javier Provencio.

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Smithason, S., Moore, S.K. & Provencio, J.J. Systemic Administration of LPS Worsens Delayed Deterioration Associated with Vasospasm After Subarachnoid Hemorrhage Through a Myeloid Cell-Dependent Mechanism. Neurocrit Care 16, 327–334 (2012). https://doi.org/10.1007/s12028-011-9651-3

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  • DOI: https://doi.org/10.1007/s12028-011-9651-3

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