Coupling Between Cerebral Blood Flow and Metabolism in the Primate: Methodological and Pharmacological Issues

Abstract

The concept of coupling between cerebral blood flow (CBF), metabolism and function was enunciated as early as 1890 by Roy and Sherrington, as follows: “We conclude then that the chemical products of cerebral metabolism contained in the lymph which bathes the walls of the arterioles of the brain can cause variations of the calibre of the cerebral vessels: that in this re-action the brain possesses an intrinsic mechanism by which its vascular supply can be varied locally in correspondence with local variations of functional activity.” However, this hypothesis remained to be tested until techniques for measurements of regional CBF and metabolism were available. A major step in this issue was achieved by the development of autoradiogra phic methods which allows the measurement of local CBF with tracers such as [¹³¹I]trifluoroiodomethane [1] or [¹⁴C]iodoantipyrine [2]. The tight relationship between regional CBF and function was demonstrated by measuring specific increases in CBF after experimentally induced local increases in functional activity that are restricted to a few defined neuroanatomical areas [3]. As an example, olfactory stimulation specifically enhanced the cerebral glucose metabolism (CMRGlu), as measured by the [¹⁴C]deoxyglucose technique, in the brain regions from the olfactory system [3]. With the advent of non invasive techniques such as positron emission tomography (PET) and, more recently, functional magnetic resonance imaging (MRI), such studies have become increasingly possible in man [4, 5]. From this succint historical description, it is evident that advances in our understanding of the relationships between CBF, metabolism and function are completely dependent on the technological progress in the measurement of each of these parameters. Such developments include improvement not only in their spatial but also in their temporal resolution.