Na-K-Cl co-transporter and its role in CSF formation

Na-K-Cl Co-Transporter, Neuropeptides, and Choroid Epithelial ‘Neuroendocrine’ Cells Impact CSF Production

The Symposium’s keynote speaker, Conrad Johanson, Ph.D., Professor of Clinical Neuroscience and the Director of Neurosurgical Research at the Brown Medical School in Providence, RI, as well as an IHRF Scientific Advisor, presented his work on the Na-K-Cl co-transporter and its role in CSF formation and ion homeostasis.

Dr. Johanson found that the Na-K-Cl transporter can bi-directionally transport sodium (Na), potassium (K) and chloride (Cl) ions into and out of CSF. These ions must be kept in homeostatic balance. It is likely that the Na-K-Cl transporter also plays an important part in modulating CSF production and perhaps, under certain circumstances, reabsorption. Neuropeptides also help to regulate CSF formation. Th ey can alter ion transport and cause neuroendocrine-like “dark cells” to develop in the epithelial layer of the choroid plexus, the site where CSF is produced in the brain. (“Dark cells” appear when there is CSF inhibition.)

According to Dr. Johanson’s research, several changes occur in a hydrocephalus model including an increase in CSF; neuroendocrine receptor plasticity in the choroid plexus; an increase in the width of the intercellular space between epithelial cells of the choroid plexus (suggesting CSF inhibition); an increase in the number of “dark cells”; and an increase in the expression of the Na-K-Cl cotransporter. These changes are thought to be signs of a decrease in CSF production in order to re-establish homeostasis (a process known as downregulating).

Downregulating is believed to occur in response to elevated intracranial pressure. If this holds true, then these findings could be a major discovery as to whether
intracranial hypertension is caused by an impediment to CSF outflow or by CSF hypersecretion. The evidence from Dr. Johanson’s study does not support the theory of CSF hypersecretion.