Simultaneous Measurement of Cerebral Blood Flow and Unidirectional Movement of Substances Across the Blood‐Brain Barrier: Theory, Method, and Application to Leucine

Abstract

The uptake of compounds by the brain depends upon cerebral blood flow. To determine the normal blood flow-cerebral extraction relationship, a method for rapid, simultaneous measurement of cerebral blood flow and brain extraction was developed and applied to blood-brain leucine transfer. Awake rats were injected i.v. with a mixture of n-[14C]butanol and [3H]leucine. The quantities of indicators accumulated over the following 5-12 s in brain and in a sample of arterial blood withdrawn at a known rate were used to determine the flux of butanol and leucine into brain. Butanol extraction was assessed independently by measuring arterial and cerebral venous concentrations of the indicator after a bolus injection. Cerebral blood flow was equal to the ratio of butanol flux into brain to butanol extraction by brain; leucine extraction was then calculated as the ratio of leucine influx to cerebral blood flow. Leucine extraction by brain and cerebral blood flow were related exponentially. The maximum velocity of active leucine transport was virtually the same at flows of 150 and 400 ml/100 g per min. The method is theoretically applicable to the measurement of the extraction of any compound from blood by brain. By measuring the normal blood flow-extraction relationship, one can differentiate changes in extraction secondary to altered flow from changes intrinsic to pathologic conditions with inconstant cerebral blood flow.