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Biomedical subjects

L Sokoloff

Publications and source records attributed to L Sokoloff.

At least 145 records · Page 8Linked to original sources
PubMed1985

Metabolic and kinetic considerations in the use of [125I]HIPDM for quantitative measurement of regional cerebral blood flow.

The metabolic degradation and the kinetics of the cerebral uptake of N,N,N'-trimethyl-N'-(2-hydroxy-3-methyl-5-[125I]iodobenzyl)-1, 3-propanediamine ([125I]HIPDM) have been studied in conscious, adult male Sprague-Dawley rats to determine its suitability as a tracer for the quantitative measurement of regional CBF (rCBF). rCBF was calculated by the indicator fractionation and the tissue equilibration methods in experiments of different durations up to 1 h. The values of rCBF obtained with [125I]HIPDM were compared with those obtained in concurrent measurements with [14C]iodoantipyrine in the same animals. Results of the experiments demonstrate that [125I]HIPDM is an inadequate tracer for use with the indicator fractionation method and that any method that employs [125I]HIPDM for the determination of rCBF must take into account its metabolic degradation, diffusion limitations, and bidirectional flux across the blood-brain barrier. With the tissue equilibration method, consistent determinations of rCBF may be possible with [125I]HIPDM by measurement of the time course of its concentration in arterial blood, corrected for the presence of 125I-labeled metabolic products, and its concentration in the brain at any time up to 1 h after its administration. The method may be adapted to measure rCBF in humans by means of single-photon emission tomography with [123I]HIPDM.

Animals↗
PubMed1985

Local cerebral glucose utilization in normal female rats: variations during the estrous cycle and comparison with males.

The quantitative 2-[14C]deoxyglucose autoradiographic method was used to study the fluctuations of energy metabolism in discrete brain regions of female rats during the estrous cycle. A consistent though statistically nonsignificant cyclic variation in average glucose utilization of the brain as a whole was observed. Highest levels of glucose utilization occurred during proestrus and metestrus, whereas lower rates were found during estrus and diestrus. Statistically significant fluctuations were found specifically in the hypothalamus and in some limbic structures. Rates of glucose utilization in the female rat brain were compared with rates in normal male rats. Statistically significant differences between males and females at any stage of the estrous cycle were confined mainly to hypothalamic areas known to be involved in the control of sexual behavior. Glucose utilization in males and females was not significantly different in most other cerebral structures.

Animals↗
PubMed1985

Influence of gamma-hydroxybutyrate on the relationship between local cerebral glucose utilization and local cerebral blood flow in the rat brain.

The relationship between local cerebral glucose utilization (LCGU) and local CBF (LCBF) was examined during the action of gamma-hydroxybutyrate (GHB) (900 mg/kg i.v.) in conscious rats. GHB induced discrepant effects on blood flow and metabolism. LCGU was markedly depressed in all structures examined, whereas LCBF was differently affected in that no related changes were observed. Global glucose utilization was markedly depressed (-51%), whereas global blood flow was not significantly altered. The marked dissociation between the changes in global glucose utilization and global blood flow induced by GHB is reflected only to a minor degree in the local values inasmuch as the correlation between LCGU and LCBF was only slightly weakened and its heterogeneity was increased.

Animals↗
PubMed1985

Differential effects of electrical stimulation of sciatic nerve on metabolic activity in spinal cord and dorsal root ganglion in the rat.

Electrical stimulation of the proximal stump of the transected sciatic nerve produces a frequency-dependent activation of glucose utilization, measured with the autoradiographic deoxy [14C]glucose method, in the dorsal horn of the spinal cord but produces no change in glucose utilization in the dorsal root ganglion cells. These results suggest that axon terminals and not the cell bodies are the sites of enhanced metabolic activity during increased functional activity of this pathway.

Afferent Pathways↗
PubMed1985

Effects of ageing on local rates of cerebral protein synthesis in Sprague-Dawley rats.

The effects of ageing on local rates of protein synthesis in 39 brain structures in resting conscious rats have been examined. Young adult rats (aged 6 months) have been compared with a group of middle-aged/aged rats (aged 15-23 months). The results show that ageing is associated with significant decreases in rates of protein synthesis in the brain as a whole as well as in several specific brain regions. Brain regions involved in visual and auditory function were selectively affected, perhaps due to a chronic lack of sensory input. Several regions involved in motor function and two areas in the limbic system had significantly decreased rates of protein synthesis in the old rats. Notably, there was a significant age-related decrease in protein synthesis in the locus coeruleus which contains the cell bodies of origin of the major ascending noradrenergic innervation of the cortex.

Aging↗
PubMed1984

Metabolic and behavioral consequences of lidocaine-kindled seizures.

Daily administration of lidocaine results in progressive increases in frequency and duration of convulsions in response to a dose of drug which was previously subconvulsive--a pharmacological kindling phenomenon. The effects of such lidocaine-kindling on local cerebral glucose utilization were determined by the 2-[14C]deoxyglucose method. Lidocaine-treated animals, in the absence of convulsions, exhibited decreased glucose utilization in most brain structures compared to saline-treated animals and showed no increase in aggressive behavior. In animals displaying lidocaine-kindled convulsions there were marked increases in glucose utilization in either the hippocampus and amygdala or in perirhinal cortical areas during the seizure administration; these animals also displayed long-lasting increases in irritable behavior. Seizure duration was positively correlated with the rate of glucose utilization in the hippocampus, amygdala and septum, but inversely correlated in several non-limbic areas. These data suggest that lidocaine-kindled seizures are highly localized to limbic and perirhinal structures and are associated with important behavioral consequences.

Aggression↗
PubMed1984

Correlation of dose-dependent effects of acute amphetamine administration on behavior and local cerebral metabolism in rats.

Rates of local cerebral glucose utilization were measured by means of the quantitative autoradiographic 2-[14C]deoxyglucose technique in conscious rats following the acute administration of D-amphetamine (0.2-5.0 mg/kg, i.v.). Changes in locomotor and stereotypic behavior in similarly treated rats were examined as well. Administration of low doses (0.2 and 0.5 mg/kg) of amphetamine resulted in increased locomotor activity, accompanied by elevations in glucose utilization limited mainly to the nucleus accumbens. A moderate dose of D-amphetamine (1.0 mg/kg) produced locomotion and stereotypic sniffing. Metabolic activity at this dose was increased in the nucleus accumbens, throughout neocortical areas, and in components of the extrapyramidal system. A high dose of amphetamine (5.0 mg/kg) produced stereotypic gnawing and licking and was associated with significant increases in glucose utilization in the extrapyramidal system, most prominently in the subthalamic nucleus. These data demonstrate that the acute administration of D-amphetamine produces effects on local cerebral glucose utilization and on behavior that differ with dose. The results also show a strong coupling between locomotion and the level of metabolic activity in the nucleus accumbens and demonstrate that the different forms of stereotypic behavior elicited by high and moderate doses of amphetamine are correlated with distinct patterns of distribution of local cerebral glucose utilization, indicating mediation by different neuronal circuits.

Animals↗
PubMed1984

Effects of acute administration of caffeine on local cerebral glucose utilization in the rat.

The quantitative 2-[14C]deoxyglucose autoradiographic method was used to study the effects of acute intravenous injections (15 min prior to study) of caffeine on brain energy metabolism. With doses of 0.1 mg/kg the effects of caffeine on cerebral glucose utilization were limited to the habenula, spinal trigeminal and paraventricular nuclei. After the 1.0 mg/kg dose significant increases were additionally seen in the caudate, ventral tegmental area and medial septum. After the injection of 10 mg/kg of caffeine, average glucose utilization of the brain as a whole was increased by 15%, and of 71 structures examined 31 structures were statistically significantly affected. Among these were all brainstem monoaminergic cell groupings, components of the extrapyramidal motor system, anterior cingulate, and medial prefrontal cortex. In the hypothalamus glucose utilization increased only in the paraventricular nucleus, arcuate nucleus, and median eminence. This study demonstrates that there is a correlation between the known stimulant effects of caffeine on behavior and widespread increases in glucose utilization throughout the brain.

Animals↗
PubMed1984

Metabolic mapping of the brain during rewarding self-stimulation.

Local rates of cerebral glucose utilization were measured in rats by the quantitative 2-deoxy-D-[14C]glucose autoradiographic method during electrical stimulation of the ventral tegmental area. Rats trained in intracranial self-stimulation showed a pattern of changes in forebrain metabolic activity distinctly different from the pattern seen in rats stimulated by the experimenter. These findings provide information about the distribution of local cerebral activity specific to reinforced instrumental behavior.

Animals↗
PubMed1984

Acute administration of high doses of estrogen increases glucose utilization throughout brain.

The effects of high intravenous doses of estradiol benzoate on local cerebral glucose utilization were studied by the [14C]2-deoxyglucose method in conscious ovariectomized adult rats. Statistically significant increases in glucose utilization averaging 20% were observed in 42 of 60 anatomically discrete regions of the estrogen-treated animals. The possible role of catechol estrogen, a potent inhibitor of catechol-O-methyltransferase, in these effects is considered.

Animals↗
PubMed1984

Modeling metabolic processes in the brain in vivo.

Positron emission tomography provides a means to measure local concentrations of positron-emitters in brain and to reconstruct pictorial images of the distribution of isotope in the brain. This capability is useful when the isotope is confined to a defined chemical species, and its concentration when combined with other measurable variables can be used to assay a physiological or biochemical process. Common variables are concentration and/or specific activity of the precursor tracer molecule in blood or plasma, the kinetics of exchange of the precursor molecule between blood and/or plasma and tissue, and the distribution space of the tracer in the tissue. These variables must be related, usually by an equation based on a kinetic model of the process under study. An example of such a method is the 2-deoxyglucose method which measures local rates of glucose utilization in brain. It was first developed with [14C]deoxyglucose and autoradiography in animals and has demonstrated a close relationship between local functional activity and glucose utilization in brain. It has proved useful to map regions of altered functional activity in the central nervous system in a variety of physiological and pharmacological states. By a combination of this technique with positron emission tomography and the positron-emitting analog, [18F]fluorodeoxyglucose, the method has been adapted for use in humans.

Animals↗
PubMed1984

Human brain glucose utilization and cognitive function in relation to age.

Brain oxidative metabolism was examined with positron emission tomography and [18F]2-deoxy-D-glucose in 40 healthy men aged 21 to 83 years, under conditions of reduced visual and auditory stimulation. The mean cerebral metabolic rate for glucose (CMRglc) equaled 4.6 to 4.7 mg X 100 gm-1 X min-1 and did not correlate significantly with age (p greater than 0.05). Regional cerebral metabolic rates for glucose (rCMRglc) and Q ratios (rCMRglc/CMRglc), which had lower coefficients of variation than did rCMRglc, also did not correlate with age. Hyperfrontality of cerebral metabolism was absent at all ages. Age decrements were demonstrated in the error score on the Benton Revised Visual Retention Test and in the Performance Subtest scaled score of the Wechsler Adult Intelligence Scale (WAIS) but not in the Verbal Subtest scaled score of the WAIS. The cognitive test scores did not correlate with brain metabolic rates. The results indicate that brain oxidative metabolism, when measured under resting conditions with reduced sensory input, is not reduced in relation to age in healthy men. Furthermore, no significant relations between intelligence and resting cerebral metabolism are evident.

Adult↗
PubMed1984

Spontaneous degenerative spinal disease in the laboratory rabbit.

The spines of 35 rabbits (32 New Zealand white and 3 AC/J), ranging in age from 3 months to 8 1/2 years, were investigated systematically for spontaneous degenerative changes. Three types of lesion were observed. (1) The nucleus pulposus underwent chondroid metaplasia throughout the length of the vertebral column by the age of 2 years. (2) Hydroxyapatite deposition was found in the nucleus pulposus in 12 of 20 animals examined roentgenographically. The lesion occurred principally in the distal thoracic segments and was first observed in 3-month-old rabbits. (3) Spondylosis occurred in each of four macerated spines from animals greater than 24 months old. Portions of the spine spared by disc calcification were affected.

Age Factors↗
PubMed1984

Attempts to combine 2-deoxyglucose autoradiography and tyrosine hydroxylase immunohistochemistry.

The possibilities were analysed to combine the 2-deoxyglucose technique and indirect immunofluorescence histochemistry using tyrosine hydroxylase antiserum, with the aim to study functional activity in immunohistochemically characterized single neurons. Since the product measured with the 2-deoxyglucose method is water soluble and since immunohistochemistry requires that sections repeatedly run through aqueous media, the 2-deoxyglucose method was carried out before fixation and immunohistochemistry. The routine rapid thaw-mounting at + 60 degrees C of sections for 2-deoxyglucose autoradiography was found not to be compatible with immunohistochemistry. Instead a new mounting technique based on "gluing" the sections on to the object slide with a mixture of a standard mounting medium (Permount) and xylene was used to avoid diffusion at this stage. Two procedures were outlined, both starting with unfixed brains cut on a cryostat. In Method I autoradiographic sheet film was used. After autoradiographic exposure, the section was immersion-fixed in formalin, processed for immunohistochemistry, analysed and photographed in a fluorescence microscope and the results compared with the autoradiographic distribution patterns on the film. However, only the low resolution of the routine 2-deoxyglucose technique was obtained, which did not allow analysis of activity in single cells. In Method II, liquid emulsion applied by the loop technique was used. After exposure, autoradiographic developing and fixation, dehydration, mounting, analysis and photography of autoradiographs in the light microscope, the cover-slip was removed, the sections rehydrated and processed for indirect immunofluorescence histochemistry. With this procedure single autoradiographically labeled cells were observed, some of which contained tyrosine hydroxylase. Thus, with Method II it may in the future be possible to monitor functional activity in single immunohistochemically identified neuronal cell bodies. In order to obtain a useful and reliable method for this purpose, however, further extensive work with regard to, for example, quantification will be required.

Animals↗