Mapping cerebral metabolic and blood flow effects of general anaesthetics

A central research problem in pharmacology has been identification of the mechanism(s) and site(s) of action of general anaesthetics within the central nervous system. Ideally, a method to investigate the effects of general anaesthetics should provide information on the functional changes occurring in neuronal cells during the anaesthetic state. Electrical activity of the primary neuronal function can not be easily mapped but drives neuronal metabolic activities. Specifically, under normal conditions glucose is almost the exclusive substrate for neuronal energetic requirements and is a major factor that regulates cerebral blood flow; hence, determination of regional cerebral metabolic rates for glucose (rCMRglc) and regional blood flow (rCBF) provide two surrogate measures of neuronal functional activities. In the late 1970s were introduced the [14C] 2-deoxy-d-glucose [1] and [14C] iodoantipyrine [2] autoradiographic techniques for the measurement of rCMRglc and rCBF in animals. Deoxyglucose is an analogue of glucose that is taken up at a fixed ratio with glucose, trapped into the neuronal cells, and not further metabolized [1]; antipyrine is a highly diffusible molecule that freely crosses the bloodbrain barrier and distributes according to blood flow [2]. Brain concentrations of both [14C] 2-deoxy-D-glucose and [14C] iodoantipyrine are hence markers of rCMRglc and rCBF and can then be determined autoradiographically.