More than a decade of study and re search has led to the refinement of an important technique for studying what takes place in a patient's brain during an epileptic seizure.
The work should in time help direct surgical treatments for these patients, but could also provide an entirely new way of administering drugs and for lifesaving monitoring. Earlier this month, Science Today looked at work done at Beaumont Hospital, Dublin, using a technique called microdialysis.
This report did not detail the central role played by Dr Billy O'Connor and his team in the department of human anatomy and physiology at the Conway Institute of Biomolecular and biomedical research at UCD.
Dr O'Connor became interested in microdialysis in 1984 while involved in a fellowship at Cambridge. It was a new technique which he found interesting. He got in touch with Prof Urban Ungerstedt at the department of physiology and pharmacology at the Karolinska Institute in Stockholm who was developing microdialysis and went there in 1987 after completing his PhD at NUI Galway.
Brain microdialysis allows researchers to monitor brain chemistry very precisely, he explains. Although the term is more familiar in connection with kidney dialysis, the microdialysis process is much the same. "The goal is to understand the chemical events that occur during epilepsy and to help develop new drugs to overcome it," Dr O'Connor says.
"If we understand the chemical events then we can develop new and better epileptic drugs."
Microdialysis involves inserting a very fine tube just a few millimetres into the brain. It causes no permanent damage to the brain tissue and is painless. The microdialysis tube is quite complex and is actually a tube within a tube, covered at its tip by a membrane which is porous. Chemicals can move freely either into or out of the tube without the need for liquid to be exchanged between the tube and brain tissue.
The substances of interest in the brain chemistry of epilepsy are glutamate and GABA, he explains. Glutamate causes excitation of brain neurons while GABA dampens this down. "They compete with each other to keep the brain under control. They skew off when a patient is having an epileptic seizure. It is the ratio of GABA to glutamate which tells you the condition of the patient."
After becoming associate professor in physiology and pharmacology at the Karolinska Institute, Dr O'Connor returned to Ireland in 1996 to set up a microdialysis research initiative with neurosurgeons at Beaumont Hospital. He found willing partners in professor of neurosurgery Mr Jack Philips and medical PhD candidate Dr Philip Thomas. Five patients have been microdialysed so far and much information is emerging, Dr O'Connor says. It takes just 40 minutes and provides four distinct brain chemistry readings.
Once the tube is inserted, a pump pushes two microlitres a minute of ringer solution, a liquid that acts like blood, down the centre of the inner tube and it returns along the space between the inner and outer tubes.
"Molecules such as neurotransmitters move from a high concentration in the brain into the porous tube and are carried away on the special solution. What we see is a distant echo of what is going on between nerves in the brain."
Back at UCD's Conway Institute, the relative levels of GABA and glutamate are measured using high pressure liquid chromatography. Team members there include Dr Pamela Magee, Dr Philip Thomas, Mr Michael Harte and Mr Alan Maguire.
Although microdialysis holds great potential for studying epilepsy, Dr O'Connor believes it will have an impact in many medical areas. It is already being used as a way to continuously monitor blood gas levels in critical newborns, a situation where repeated withdrawal of blood for testing would be dangerous. Because chemicals can diffuse in either direction across the porous membrane, he also sees its value in very localised and highly controllable drug delivery. "This will revolutionise our approach to the treatment of not only epilepsy but Parkinson's disease and schizophrenia as well."