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Cerebrospinal Fluid from Aneurysmal Subarachnoid Hemorrhage Patients Leads to Hydrocephalus in Nude Mice

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Abstract

Objective

Our prior studies have found that intracerebroventricular injection of blood components can cause hydrocephalus and choroid plexus epiplexus cell activation in rats. To minimize the cross-species reaction, the current study examines whether intraventricular injection of acellular components of cerebrospinal fluid (CSF) from subarachnoid hemorrhage patients can cause hydrocephalus and epiplexus macrophage activation in nude mice which lack a T cell inflammatory response.

Methods

Adult male nude mice received intraventricular injections of acellular CSF from subarachnoid hemorrhage patients or a control patient. All mice had preoperative magnetic resonance imaging as baseline and postoperative scans at 24 h after CSF injection to determine ventricular volume. Brains were harvested at 24 h for brain histology, immunohistochemistry, and electron microscopy.

Results

Intraventricular injection of CSF from two of five subarachnoid hemorrhage patients obtained < 48 h from ictus resulted in ventricular enlargement at 24 h. CSF-related hydrocephalus was associated with activation of epiplexus macrophages and ependymal injury.

Conclusions

Components of the acellular CSF of subarachnoid hemorrhage patients can cause epiplexus macrophage activation, ependymal cell damage, and ventricular enlargement in nude mice. This may serve as a unique model to study mechanisms of hydrocephalus development following subarachnoid hemorrhage.

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Author Contributions

Study was conceived and designed by GX and ASP. Data were acquired, analyzed, and interpreted by SW, JW, and YH. Statistical expertise was provided by SW. The article was drafted by SW, RFK, GX, and ASP. Supervision was provided by GX. All authors reviewed the final version, which was approved on behalf of all authors by GX and ASP.

Sources of Support

YH, RFK, GX, and ASP were supported by grants NS-090925, NS-096917, NS-106746, NS-108042, NS-112394 and NS-116786 from the National Institutes of Health.

Conflicts of Interest

The authors report no conflicts of interest.

Ethical Approval

The study was approved by the University of Michigan Institutional Review Board. Animal use protocols were approved by the University of Michigan Committee on the Use and Care of Animals.

Informed Consent

Informed consent was obtained from the patients whose cerebrospinal fluid was sampled.

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Author notes

  1. Guohua Xi and Aditya S. Pandey: Co-senior authors.

Authors and Affiliations

  1. Department of Neurosurgery, University of Michigan, Ann Arbor, MI, USA

    Shu Wan, Jialiang Wei, Ya Hua, Sravanthi Koduri & Richard F. Keep

  2. Brain Center, Zhejiang Hospital, Hangzhou, Zhejiang Province, China

    Shu Wan

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

    Guohua Xi

  4. Department of Neurosurgery, University of Michigan, 3552 Taubman Center, 1500 E. Medical Center Drive, Ann Arbor, MI, 48109, USA

    Aditya S. Pandey

Authors
  1. Shu Wan
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  2. Jialiang Wei
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  3. Ya Hua
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  4. Sravanthi Koduri
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  5. Richard F. Keep
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  6. Guohua Xi
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  7. Aditya S. Pandey
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Corresponding authors

Correspondence to Guohua Xi or Aditya S. Pandey.

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Wan, S., Wei, J., Hua, Y. et al. Cerebrospinal Fluid from Aneurysmal Subarachnoid Hemorrhage Patients Leads to Hydrocephalus in Nude Mice. Neurocrit Care 34, 423–431 (2021). https://doi.org/10.1007/s12028-020-01031-0

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  • DOI: https://doi.org/10.1007/s12028-020-01031-0

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