Cerebral edema tops menu for VUMC's first brain research dinner
Dr. Kenneth Smithson (left) and Kevin Strange, Ph.D., are the co-organizers of the "Bench-to-Bedside Brain Dinner" series, which kicked off last week. (Photo by Anne Rayner)
Basic and clinical neuroscience investigators passed around the salt, pepper, hot sauce and brain tidbits at Vanderbilt University Medical Center's first "Bench-to-Bedside Brain Dinner."
The conferences, planned for the last Thursday of each month, provide the setting for informal conversations between clinical and basic science researchers interested in the human brain and sensory systems. These conversations, organizers say, will prompt the transfer of ideas and discoveries back and forth between the laboratory and the clinic.
Dr. Kenneth G. Smithson, assistant professor of Anesthesiology, and Kevin Strange, Ph.D., professor of Anesthesiology and Pharmacology, presented the results of their collaborative efforts to understand and treat cerebral edema, or brain swelling.
"Cerebral edema is pervasive in neurological injury," Smithson said. "About one million Americans seek help each year for a traumatic brain injury with consequent cerebral edema, and even with our best medical management, 30 percent of these people are left severely disabled. Traumatic brain injury remains the leading cause of death in young people between the ages of 18 and 35 years old."
Smithson and Strange are the co-organizers of the "Bench-to-Bedside Brain Dinner" series. Informal conversations between the two sparked questions about the rationale for using the diuretic drugs furosemide and bumetanide to reduce increased pressure inside the cranium.
"The model was that these drugs reduced cerebrospinal fluid (CSF) production by blocking an ion cotransporter on the blood side of choroid plexus cells," Smithson said.
The choroid plexus separates the brain's cavities from the blood and is primarily responsible for secreting CSF. The diuretic-sensitive cotransporter was believed to move salt ions for secretion in CSF from the blood into choroid plexus cells.
Strange spotted a flaw in this model.
"The ion cotransporter the drugs block is on the wrong side of the cell to be participating in CSF production," Strange said. "We became interested in understanding the true function of the cotransporter."
Strange has studied individual cells of the choroid plexus, using cell volume change as a readout for transporter activity.
"We're proposing that the cotransporter is really functioning to buffer CSF and brain potassium levels. Potassium levels have to be tightly controlled for the brain to function correctly," Strange said.
Strange and Smithson conclude that there is no basis for using furosemide and bumetanide to inhibit CSF secretion. The drugs must be using some other mechanism to lower intracranial pressure, they said.
Discovering the true pathways responsible for CSF secretion will provide new targets for the therapeutic management of cerebral edema, they said.