Hydrocephalus is a neurological condition characterized by the overproduction, underabsorption or obstruction of cerebrospinal fluid (CSF) flow in the brain’s ventricles, often resulting in increased intracranial pressure and ventricular enlargement. This condition can affect individuals of all ages leading to developmental delays, cognitive impairment, and death in severe cases. Current treatment options, primarily surgical, rely on shunt placement or endoscopic third ventriculostomy, both of which carry risks of complications, malfunction, and revision surgeries. The majority of CSF is produced in the choroid plexus, which is composed of blood vessels and a specialized epithelial layer forming the blood-CSF barrier. To improve our understanding of the molecular basis of hydrocephalus, this study investigates ion transporters in the choroid plexus epithelial cells that regulate CSF production and homeostasis. One key transporter that has previously been implicated in CSF production is NKCC1, a sodium-potassium-chloride cotransporter that contributes to the osmotic. Changes in NKCC1 activity may influence the movement of ions and water across the apical membrane. To investigate whether NKCC1 contributes to CSF accumulation, we hypothesize that in a genetic model the hydrocephalic (TMEM 67-/-) rats will exhibit altered NKCC1 expression or phosphorylation compared to wild-type (TMEM 67+/+) rats. Immunohistochemistry was performed on brain tissue sections, focused on the choroid plexus, collected from the untreated wild-type and homozygous TMEM67 rats to compare the expression and phosphorylation on NKCC1. The results showed no significant difference in NKCC1 expression or phosphorylation between the wild-type and homozygous rats. This suggests that in this vivo model the transporter may not be the primary factor driving CSF accumulation. Future directions will include investigating protein kinase STE20/SPS1-related proline/alanine-rich kinase (SPAK). SPAK is an important part of the WNK-SPAK/OSR1 signaling pathway that phosphorylates NKCC1, as well as other important transporters in the pathway. These studies were supported by DoD Congressionally Directed Medical Research Program Grants #HT94252310296 and #HT94252310401 (BBY) and by an Indiana University, Indianapolis Layered Learning Grant and funds from the Undergraduate Research Opportunities Program. This abstract was presented at the American Physiology Summit 2026 and is only available in HTML format. There is no downloadable file or PDF version. The Physiology editorial board was not involved in the peer review process.
Kaur et al. (Fri,) studied this question.
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