Yale researchers will test the feasibility of using multiphoton fluorescence imaging in animal model tissue of epilepsy to determine whether this technique can reveal how brain metabolism is slowed in this disease and how this process contributes to seizure development.
Research has demonstrated that brain metabolism is slowed in people with epilepsy, but the reasons for this hypometabolism, and its consequences for seizure development, are not currently understood. Neurons that communicate with one another through release of the excitatory neurotransmitter glutamate depend upon astrocytes to clear away excess glutamate from the synapses that connect neurons to one another. If glutamate is insufficiently cleared, neurons may become overstimulated, leading to seizures. The investigators hypothesize that malfunctioning astrocytes have defects in their mitochondria, a component that ordinarily produces energy for nerve cells.
They will investigate this hypothesis using multiphoton fluorescence microscopy to observe the functioning of astrocytes and neurons in animal model epilepsy tissue. This imaging technique can measure exactly how long it takes, after stimulating a molecule (called NADH) that is involved in energy metabolism in mitochondria, to emit fluorescence. Through this imaging technique, they will determine whether there are too few NADH molecules, or whether the levels are normal but the molecules are malfunctioning.
Significance: If the researchers demonstrate the feasibility of using this imaging technique to identify the basis of metabolic dysfunction in astrocytes, the technique then can be tested in tissue removed from patients undergoing surgery for intractable epilepsy. Ultimately, the findings may lead to development of drugs that specifically target metabolic dysfunction of astrocytes. Moreover, this imaging technique could be used by neurosurgeons prior to surgery for intractable epilepsy, as a marker to more accurately differentiate normal from epileptic brain tissue.