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We applied a multiple regression/discriminant analysis to resting metabolic data from patients with first hemiparetic suprathalamic infarctions to determine if metabolic interdependencies, which may separate recovered (N=12) from nonrecovered (N=9) patients, suggest important motor-recovery pathways. Recovered, vs. nonrecovered, patients showed an enhanced ipsilesional thalamic-contralesional cerebellar metabolic interdependency. This pattern correctly classified 91% of recovered and 88% of nonrecovered patients. Metabolic interactions involving bilateral supplementary motor area, ipsilesional thalamus, and contralesional cerebellum distinguished all recovered patients from age/sex-matched controls (N=12). These results suggest that altered functional interactions in thalamic circuitry may reflect plastic reorganization associated with motor recovery from hemiparesis.

Microvascular bed structure and functions are known to vary throughout the brain. Microvascular responses to high doses of pentobarbital sodium might therefore differ among brain areas. This possibility was examined by measuring local cerebral blood flow (LCBF) with [14C]iodoantipyrine in 52 brain areas at 5, 10, 25, and 60 min after intraperitoneal administration of pentobarbital (50 mg/kg). From 5 to 60 min, LCBF was significantly lowered in 17 of 25 forebrain gray matter areas but in only 1 of 18 hindbrain gray matter structures, the pontine nuclei. Smaller, shorter duration lowering of LCBF was also observed in ten other brain areas. In both control and treated rats, LCBF was found to vary within individual brain structures. The pattern of these LCBF variations was columnar in the cerebral cortex and the hippocampus but was patchy in the caudate-putamen, thalamus, and inferior colliculus. These results indicate that pentobarbital anesthesia more strongly alters LCBF in the forebrain than in the hindbrain and produces different patterns of changes in LCBF than in local cerebral glucose utilization, which was measured with 2-deoxyglucose in a companion study.

Studies with positron-emission tomography have indicated that muscarinic acetylcholine receptors may be involved in the mechanism of enhancement of cerebral blood flow (CBF) by neuronal functional activation. We examined the effects of muscarinic receptor blockade by scopolamine on the local CBF responses to vibrissal stimulation in the whisker-to-barrel cortex sensory pathway in unanesthetized rats. Local CBF was measured by the quantitative autoradiographic [(14)C]iodoantipyrine method. Scopolamine (0.4 or 0.8 mg/kg) was injected i.v. 30 min before measurement of local CBF; control rats received equivalent volumes of physiological saline. Vibrissae on the left side of the face were stroked continuously throughout the 1-min period of measurement of CBF. Local CBF was determined bilaterally in four structures of the pathway, i.e., spinal and principal sensory trigeminal nuclei, ventral posteromedial thalamic nucleus, and barrel field of the sensory cortex, as well as in four representative structures unrelated to the pathway. The higher dose of scopolamine raised baseline CBF in the two trigeminal nuclei, but neither dose diminished the percentage of increases in local CBF because of vibrissal stimulation in any of the stations of the pathway. These results do not support involvement of muscarinic receptors in the mechanism of enhancement of local CBF by functional neuronal activation, at least not in the whisker-barrel cortex sensory pathway in the unanesthetized rat.

To assess the contributions of the basal forebrain cholinergic nuclei to visual recognition memory in macaques, we compared the effects of lesions of (a) the nucleus basalis of Meynert, (b) the medial septal and diagonal band nuclei, and (c) all nuclei combined on performance of delayed nonmatching-to-sample with trial-unique stimuli. Whereas monkeys with the separate lesions did not differ from each other or from normal control animals, those with combined lesions showed a significant impairment. With time and extended practice, however, the performance of the animals with combined lesions recovered to normal levels. During the recovery period, these monkeys showed an initially increased sensitivity to scopolamine that later dissipated, at which time they also failed to show the improvement that follows physostigmine administration in normal animals. Postmortem assessment of cortical choline acetyltransferase activity revealed that only the group with combined lesions had significant depletion of this enzyme. The results suggest that (1) the basal forebrain cholinergic system participates in mnemonic processes in primates and that (2) extensive damage to this system is necessary before impairments in recognition memory, even transient ones, can be observed.

It is sometimes desirable to obtain a specified blood level which obeys a prescribed mathematical form. Following an approach based on impulse analysis via Laplace Transform techniques, a general method for an input injection schedule which will achieve this goal is derived. Specific infusion schedules are given which attain blood levels that are constant, increase linearly, decay exponentially, and increase exponentially. Further, simpler approximate infusion schedules are also derived whose outputs achieve the desired function after a short time. Two illustrative experimental examples-one for [14C]EDTA-Ca in anesthetized rhesus monkeys and the other for 2-deoxy-D-[1-14C]glucose in the conscious rat-are presented in detail. The assumptions are discussed and an error analysis is performed.

Am. L Physinl.: 2kart I&c*. 2hyCL $3): H299-~3~1j 1978. - Vascular permeability P in different cerebral regions of the conscious rat was determined, independently of blood flow, for “C tracers of glycerol, mannitol, sucrose, and inulin. A tracer was injected intravenously, arterial plasma concentrations were monitored, and regional brain concentrations were measured at specific times thereafter. A plasma-brain two-compartment model was used to calculate mean regional values of P, letting capillary area equal 240 cm”*g? P was Z4 X 10+ cm * s-* for glycerol, 0.95-1.4 X lop7 for mannitol, 2.53,O x 10mH for sucrose, and 1.0-1.4 x IO-!) for inulin. Cerebrovascular permeability coefficients correspond to coefficients at single cell membranes and lipid bilayers, but are 1,000 times less than at muscle capillaries, The relation between cerebrovascular prmeability and octanol/water partition suggests that saccharides diffuse into the brain through homogeneous endothelial cell membranes and not through capillary pores or by means of vesicles. Estimated cerebral distribution volumes for the tracers indicate that glycerol distributes rapidly within the brain extracellular and intracellular compartments and may be incorporated into the metabolic pool, that mannitol distributes extracellularly and partially intracellularly, and that sucrose remains within the extracellular space.

Cerebrovascular permeability to 14C-sucrose was measured independently of cerebral blood flow in the rat, following unilateral osmotic opening of the blood-brain barrier by hypertonic arabinose solution. An increase in regional permeability to 14C-sucrose was correlated with the extent of brain staining by intravascular Evans blue-albumin, a visual barrier tracer. To obtain the product of capillary permeability and surface area, 14C-sucrose was injected intravenously, the arterial plasma concentration curve was determined and integrated over a 10-minute period, and brain parenchymal concentration was calculated after subtracting vascular radioactivity from net tissue radioactivity. Conditions were chosen so that a simple diffusion equation could be applied to exchange between plasma and brain compartments, in the absence of back flux from brain. The method should be of use for studying effects of microwaves on the cerebral vasculature.

1. Distributions of dense bodies per platelet were evaluated in unstimulated human platelets and in platelets stimulated to secrete by the addition of varying amounts of thrombin or the ionophore A23187. Since distributions were not Gaussian, they were compared by non-parametric methods. 2. Most distribution obtained following varying levels of dense-body release differed significantly from the control (unstimulated) distribution. In general, distribution from points widely separated in terms of per cent release of total dense-body content also differed significantly. Distributions obtained at points where the total number of dense bodies lost was approximately the same did not differ significantly, regardless of the drug and incubation conditions used to produce the dense-body loss. 3. Dense bodies were lose from platelets during the secretory process (measured as the release of either calcium or ATP), and the number of dense bodies lost correlated at a significant level with the amounts of both substances secreted. 4. Following maximal secretion produced by either thrombin or A23187, a population of dense bodies (refractory dense bodies) remained in platelets. The refractory dense bodies could not have been distributed uniformly among the control populations of either platelets or dense bodies. The distribution of refractory dense bodies could, however, be described by a model in which platelets containing large numbers of dense bodies had a greater proportion of their dense-body complement refractory than did platelets containing fewer dense bodies.

A four-compartment model was derived to analyze drug exchange among cerebral capillary plasma, cerebrospinal fluid (CSF), and the brain extracellular and intracellular (or bound) compartments. Equations that were derived incorporated the factor of cerebral blood flow. They were fit by nonlinear least squares to measured brain, plasma, and CSF (when available) concentrations of [14C]urea in the rat, in response to a step increase in plasma concentration, to intravenous infusion, or to a bolus injection of tracer. Best-fit values for the transfer constants were consistent among the three administrative regimens and agreed with published values, when available. Expressions also were derived and numerically evaluated for the lower limit of the brain extracellular space, for half times of brain [14C]urea uptake, and for the steady-state brain/plasma distribution volume. The model should make it possible to use transfer constants obtained for a given drug from one study (e.g., constant plasma concentration) to predict brain concentrations from measured plasma concentrations in other acute or chronic studies.