The autoradiographic diffusible tracer technique for the measurement of local cerebral blood flow was originally designed for use with the radioactive, inert gas 131I-labeled trifluoroiodomethane and is applicable only with tracers that exhibit unrestricted diffusion through the blood-brain barrier. Because of the technical problems associated with the use of gaseous tracers, a suitable nonvolatile tracer has been sought. [14C] Antipyrine has been used previously and found to be unsuitable because of limitations in its diffusion through the blood-brain barrier. An analogue of [14C]antipyrine, iodo [14C]antipyrine, exhibits higher partition coefficients than [14C]antipyrine between nonpolar solvents and water and might, therefore, be expected to diffuse more freely through the barrier. Its use as the tracer in the local blood flow technique leads to values considerably above those obtained with [14C]antipyrine in the rat and cat and essentially the same as those obtained with the gas trifluoro[131I]iodomethane in the cat. Iodo[14C]antipyrine appears, therefore, to be a satisfactory nonvolatile tracer for the measurement of local cerebral blood flow.

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Functional brain mapping based on changes in local cerebral blood flow (lCBF) or glucose utilization (lCMRglc) induced by functional activation is generally carried out in animals under anesthesia, usually ␣-chloralose because of its lesser effects on cardiovascular, respiratory, and reflex functions. Results of studies on the role of nitric oxide (NO) in the mechanism of functional activation of lCBF have differed in unanesthetized and anesthetized animals. NO synthase inhibition markedly attenuates or eliminates the lCBF responses in anesthetized animals but not in unanesthetized animals. The present study examines in conscious rats and rats anesthetized with ␣-chloralose the effects of vibrissal stimulation on lCMRglc and lCBF in the whisker-to-barrel cortex pathway and on the effects of NO synthase inhibition with N G -nitro-L-arginine methyl ester (L-NAME) on the magnitude of the responses. Anesthesia markedly reduced the lCBF and lCMRglc responses in the ventral posteromedial thalamic nucleus and barrel cortex but not in the spinal and principal trigeminal nuclei. L-NAME did not alter the lCBF responses in any of the structures of the pathway in the unanesthetized rats and also not in the trigeminal nuclei of the anesthetized rats. In the thalamus and sensory cortex of the anesthetized rats, where the lCBF responses to stimulation had already been drastically diminished by the anesthesia, L-NAME treatment resulted in loss of statistically significant activation of lCBF by vibrissal stimulation. These results indicate that NO does not mediate functional activation of lCBF under physiological conditions. whisker-to-barrel cortex pathway ͉ cerebral glucose utilization ͉ deoxy[ 14 C]glucose ͉ functional brain imaging ͉ iodo[ 14 C]antipyrine N euronal functional activation is normally associated with increases in local cerebral glucose utilization (lCMR glc ) and blood flow (lCBF) in anatomic units of the activated neural pathways. These associations are now widely exploited to map regions of the brain involved in specific neural and cognitive processes. The mechanisms underlying the functional activation of lCMR glc are reasonably well understood. Glucose utilization is increased by functional activation in direct proportion to the increases in spike frequency in the afferent inputs to the activated areas, and the increases are localized in neuropil and not perikarya (1, 2). The increases in lCMR glc appear to result mainly from activation of Na ϩ ,K ϩ -ATPase activity (2, 3), needed to restore ionic gradients in the neuronal elements degraded by the spike activity. Neuropil contains not only axonal and dendritic processes but also astroglial processes, and glutamate stimulates glucose utilization in astroglia, also due in part to activation of Na ϩ ,K ϩ -ATPase activity by coupled uptake of Na ϩ ions with the glutamate released during functional activation (4, 5). Glucose utilization is also increased to support the ATPdependent conversion to glutamine of the glutamate taken up by the astroglia (6).The mechan...

The [14C]deoxyglucose method for quantitative determination of local cerebral glucose utilization was extended to the macaque monkey. The necessary constants required by its operational equation were evaluated. The lumped constant, measured in 7 normal conscious monkeys, was found to equal 0.344 (SEM, +/- 0.036). The rate constants were also estimated and found to be very similar to those obtained previously in the rat. With these essential constants evaluated, the method was applied to normal conscious monkeys. Local cerebral glucose utilization was found to vary marked throughout the brain but to fall within two distributions, a higher one in gray matter and lower one in white matter. In general, the values fell in a range to be expected from previous measurements of average energy metabolism in the brain as a whole. The values were considerably lower than those observed previously in the conscious rat. Marked heterogeneity of rates of glucose utilization were observed in a number of anatomical structures. In some cases the patterns of heterogeneity were consistent with known histological cytoarchitecture; in others the heterogeneity did not conform with known cytoarchitectural features but corresponded to patterns previously demonstrated by electrophysiological techniques. Many of the regions of the cerebral cortex showed columnar patterns of distribution of higher and lower rates of glucose utilization. These may be a metabolic reflection of the columnar organization of function within the cerebral cortex.

ABSTRACT[14C]deoxyglucose-6-phosphate, the fractional turnover rate of the free [14C]deoxyglucose pool in the tissue, and the ratios of the Michaelis-Menten kinetic constants of hexokinase for deoxyglucose and glucose (6). The key to the localization possible with the method is a quantitative autoradiographic technique for the measurement of local tissue concentrations of ['4C]deoxyglucose-6-phosphate. Even without the quantification, however, the autoradiographs are themselves pictorial representations of the local rates of glucose consumption throughout the brain. Inasmuch as local energy metabolism in the brain, as in other tissues, is closely coupled to'local functional activity, the method has proved effective for the delineation of local cerebral regions with altered functional activity in response to experimentally modified physiological states (7).The binocular visual system of the monkey appeared to offer an appropriately intricate METHODSRhesus monkeys of either sex weighing 2.5-3.5 kg were used in these studies. Polyethylene catheters were inserted in a femoral artery and vein after light halothane and nitrous oxide anesthesia, and the animals were then placed in a restraining chair and allowed to recover from the anesthesia for at least 4 hr. The experimental period was initiated by the intravenous injection of a pulse of 100 ,uCi/kg of ['4C]deoxyglucose (specific activity, 50-55 mCi/mmol; New England Nuclear Corp., Boston, Mass.) contained in 3 ml of normal saline. In most of the animals, timed arterial blood samples were drawn during the ensuing 45 min period for the measurement of the arterial 4230

An enzymatic preparation from human brain converts tryptamine to tryptoline (9H-1,2,3,4-tetrahydropyrido(3,4-b)indole) in the presence of 5-methyltetrahydrofolic acid. Similarly, N-methyltryptamine and 5-hydroxytryptamine yield 1-methyltryptoline and 5-hydroxytryptoline, respectively. Neither in vitro nor in vivo formation of these compounds by human tissues has been described.

Local cerebral blood flow was measured in the mouse by means of the [14C]iodoantipyrine method. This method has been previously used in the monkey, dog, cat, and rat, but its application to small mammals such as the mouse requires special attention to potential sources of error. The small size of the mouse brain requires special attention to the rapid removal and freezing of the brain to minimize effects of postmortem diffusion of tracer in the tissue. Because of the relatively low diameter/length ratios of the catheters needed for arterial sampling in small animals, substantial errors can occur in the determination of the time course of the [14C]iodoantipyrine concentration in the arterial blood unless corrections for lag time and dead space washout in the catheter are properly applied. Local cerebral blood flow was measured in seven awake mice with appropriate care to minimize these sources of error. The values were found to vary from 48 ml/100 g/min in the corpus callosum to 198 ml/100 g/min in the inferior colliculus. The results demonstrate that the [14C]iodoantipyrine method can be used to measure local cerebral blood flow in the mouse and that the values in that species are, in general, somewhat higher than those in the rat.

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