Inflammation in acquired hydrocephalus: pathogenic mechanisms and therapeutic targets

Jason K. Karimy, Benjamin C. Reeves, Eyiyemisi Damisah, Phan Q. Duy, Prince Antwi, Wyatt David, Kevin Wang, Steven J. Schiff, David D. Limbrick, Seth L. Alper, Benjamin C. Warf, Maiken Nedergaard, J. Marc Simard, Kristopher T. Kahle

Research output: Contribution to journalReview article

1 Scopus citations

Abstract

Hydrocephalus is the most common neurosurgical disorder worldwide and is characterized by enlargement of the cerebrospinal fluid (CSF)-filled brain ventricles resulting from failed CSF homeostasis. Since the 1840s, physicians have observed inflammation in the brain and the CSF spaces in both posthaemorrhagic hydrocephalus (PHH) and postinfectious hydrocephalus (PIH). Reparative inflammation is an important protective response that eliminates foreign organisms, damaged cells and physical irritants; however, inappropriately triggered or sustained inflammation can respectively initiate or propagate disease. Recent data have begun to uncover the molecular mechanisms by which inflammation — driven by Toll-like receptor 4-regulated cytokines, immune cells and signalling pathways — contributes to the pathogenesis of hydrocephalus. We propose that therapeutic approaches that target inflammatory mediators in both PHH and PIH could address the multiple drivers of disease, including choroid plexus CSF hypersecretion, ependymal denudation, and damage and scarring of intraventricular and parenchymal (glia–lymphatic) CSF pathways. Here, we review the evidence for a prominent role of inflammation in the pathogenic mechanism of PHH and PIH and highlight promising targets for therapeutic intervention. Focusing research efforts on inflammation could shift our view of hydrocephalus from that of a lifelong neurosurgical disorder to that of a preventable neuroinflammatory condition.

Original languageEnglish (US)
Pages (from-to)285-296
Number of pages12
JournalNature Reviews Neurology
Volume16
Issue number5
DOIs
StatePublished - May 1 2020

All Science Journal Classification (ASJC) codes

  • Clinical Neurology
  • Cellular and Molecular Neuroscience

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    Karimy, J. K., Reeves, B. C., Damisah, E., Duy, P. Q., Antwi, P., David, W., Wang, K., Schiff, S. J., Limbrick, D. D., Alper, S. L., Warf, B. C., Nedergaard, M., Simard, J. M., & Kahle, K. T. (2020). Inflammation in acquired hydrocephalus: pathogenic mechanisms and therapeutic targets. Nature Reviews Neurology, 16(5), 285-296. https://doi.org/10.1038/s41582-020-0321-y