Inflammation-dependent cerebrospinal fluid hypersecretion by the choroid plexus epithelium in posthemorrhagic hydrocephalus
Nature Medicine 23, 997 (2017).
doi:10.1038/nm.4361
Authors: Jason K Karimy, Jinwei Zhang, David B Kurland, Brianna Carusillo Theriault, Daniel Duran, Jesse A Stokum, Charuta Gavankar Furey, Xu Zhou, M Shahid Mansuri, Julio Montejo, Alberto Vera, Michael L DiLuna, Eric Delpire, Seth L Alper, Murat Gunel, Volodymyr Gerzanich, Ruslan Medzhitov, J Marc Simard & Kristopher T Kahle
The choroid plexus epithelium (CPE) secretes higher volumes of fluid (cerebrospinal fluid, CSF) than any other epithelium and simultaneously functions as the blood–CSF barrier to gate immune cell entry into the central nervous system. Posthemorrhagic hydrocephalus (PHH), an expansion of the cerebral ventricles due to CSF accumulation following intraventricular hemorrhage (IVH), is a common disease usually treated by suboptimal CSF shunting techniques. PHH is classically attributed to primary impairments in CSF reabsorption, but little experimental evidence supports this concept. In contrast, the potential contribution of CSF secretion to PHH has received little attention. In a rat model of PHH, we demonstrate that IVH causes a Toll-like receptor 4 (TLR4)- and NF-κB-dependent inflammatory response in the CPE that is associated with a ∼3-fold increase in bumetanide-sensitive CSF secretion. IVH-induced hypersecretion of CSF is mediated by TLR4-dependent activation of the Ste20-type stress kinase SPAK, which binds, phosphorylates, and stimulates the NKCC1 co-transporter at the C...
Source: Nature Medicine - Category: General Medicine Authors: Jason K Karimy Jinwei Zhang David B Kurland Brianna Carusillo Theriault Daniel Duran Jesse A Stokum Charuta Gavankar Furey Xu Zhou M Shahid Mansuri Julio Montejo Alberto Vera Michael L DiLuna Eric Delpire Seth L Alper Murat Gunel Volodymyr Gerzanich Rusla Tags: Letter Source Type: research
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