Monitoring cellular edema at single-neuron level by electrical resistance measurements

Electrical resistance measurements have been used for investigating extracellular volume fraction (EVF) of brain tissue. Conventional techniques using multiple metal electrodes are limited in their spatial resolution, and thus not suitable for detecting local EVF changes at cellular level. We used a multibarrelled glass microelectrode to monitor cellular swelling locally at single-neuron level. The microelectrode was placed in CA1 region of the rat hippocampus, in situ. A constant current pulse was applied between one of the barrels and a reference electrode placed in the neck. The resultant voltage drop, which was directly proportional to the resistance of the immediate environment surrounding the tip of the microelectrode, was recorded through another barrel. A third barrel was used for iontophoretic injection of N-methyl-D-aspartate (NMDA) for inducing local cellular edema. The effect of diffuse edema induced by bilateral carotid artery ligation on EVF was also investigated. NMDA application increased the local tissue resistance by 2.0-, and ischemia, by 3.4-folds. We conclude that the method described can detect changes in EVF of minute volumes of brain tissue, and is suitable for monitoring very local effects of drugs or changes in the metabolism on cell volume.