Biomedical subjects

A Nehlig

Publications and source records attributed to A Nehlig.

At least 109 records · Page 6Linked to original sources

PubMed1990

Consequences of chronic phenobarbital treatment on local cerebral glucose utilization in the developing rat.

The influence of a chronic phenobarbital (PhB) treatment on postnatal evolution of local cerebral metabolic rates for glucose (LCMRglc) was studied in 58 cerebral structures of freely moving rats. The animals received a daily subcutaneous injection of PhB at a dose of 50 mg/kg between days 2 and 35 or an equivalent volume of saline for controls and were studied at 5 postnatal stages, i.e. 10, 14, 17, 21 and 35 days, and at the adult stage. Body and brain weights were both reduced by 6-21% over the whole period studied. PhB exposure induced significant decreases in LCMRglc during the period of pharmacological treatment, i.e. until 35 days, except at the stage of 17 days as well as long-term reductions in LCMRglc of adult rats in 36 out of the 58 brain regions studied. These decreases affected all systems studied, sensory systems as well as limbic, hypothalamic, motor and white matter areas. In addition to a growth retardation, PhB also seemed to be able to induce a delay in the acquisition of auditory function which matures early during postnatal life. The long-term deficits in cerebral energy metabolism due to PhB in the adult rat also confirm the behavioral deficits which have been shown previously after early PhB exposure.

Aging↗

PubMed1990

Effects of caffeine, L-phenylisopropyladenosine and their combination on local cerebral blood flow in the rat.

The quantitative [14C]iodoantipyrine autoradiographic method was applied to study the effects of acute administration of caffeine and L-phenylisopropyladenosine (LPIA) separately or in combination on local cerebral blood flow in the rat. After the injection of caffeine, cerebral blood flow rates were decreased in 13 out of the 61 structures studied, mainly in motor and auditory areas. The administration of LPIA induced a general decrease in local cerebral blood flow, which was significant in only 4 regions. The combined administration of caffeine and LPIA induced decreases in blood flow rates in 17 brain areas, motor, limbic and hypothalamic structures and increases in 3 limbic regions. The results confirm previous data on the effect of caffeine on cerebral circulation. The consequences of LPIA administration on blood flow may originate partly from peripheral effects and may also be the reflection of the reduction in the energy demand of the brain. Finally, LPIA also seems to be able to modulate caffeine effects on local cerebral blood flow when injected simultaneously with caffeine.

Adenosine↗

PubMed1990

Influence of early neonatal phenobarbital exposure on cerebral energy metabolism and behavior.

The influence of an early chronic phenobarbital (PhB) exposure on local cerebral glucose utilization (LCGU) and on behavior was studied in the rat. The animals were treated from Postnatal Day 2 to Postnatal Day 35 by a daily injection of 50 mg/kg PhB or by saline and tested between 10 and 35 days for short-term effects of the drug on LCGU and between 70 and 90 days for long-term effects of PhB on LCGU and behavior. PhB induced short- and long-lasting reductions in the overall rates of LCGU in hippocampal and cerebellar areas, but no significant changes in LCGU in the different cell layers of these two cerebral areas. PhB also changed the pattern of maturation of the rates of LCGU as compared to control subjects. The barbiturate treatment induced a decrease in the exploratory behavior of PhB- as compared to saline-treated rats in the open field, as well as a significant 25% decrease in the rate of spontaneous alternation with delay. In addition, PhB-treated rats needed significantly more time than control animals to perform their trials in the nonrewarded T maze testing. However, the neonatal barbiturate exposure did not induce changes in performances of adult rats in the rewarded eight arm maze. The results of the present study show that there is no apparent correlation between the rates of energy metabolism in the hippocampus and the impairment of learning abilities of adult rats in behavioral tests related to the hippocampus.

Animals↗

PubMed1989

Effects of caffeine and doxapram perfusion on local cerebral glucose utilization in conscious rats.

The quantitative autoradiographic 2-[14C]deoxyglucose method was used to measure the effects of a continuous infusion of the respiratory stimulants, caffeine or doxapram, 18 mg/kg per h, on local cerebral glucose utilization in the adult male rat. Local cerebral glucose utilization was measured in 54 cerebral structures from different systems. Caffeine induced widespread increases in energy metabolism, resulting in a significant increase in glucose utilization in 25 structures out of the 54 studied. These increases were distributed within all systems studied, sensory, extrapyramidal motor, limbic and hypothalamic systems. In addition, caffeine induced a non-significant, 10-15%, increase in local cerebral glucose utilization in central respiratory areas. Doxapram infusion did not change the rates of glucose utilization in any of the structures. The rates of local cerebral glucose utilization were significantly lower after doxapram than after caffeine exposure in five cerebral areas, among which were three central respiratory areas. The results confirm the absence of side-effects of doxapram as compared to caffeine when used as respiratory stimulant, especially in neonates. These results also favor a preferentially central action of caffeine on respiratory areas and a more peripheral action of doxapram on chemoreceptors, at least at therapeutic levels.

Animals↗

PubMed1989

Postnatal changes in local cerebral blood flow measured by the quantitative autoradiographic [14C]iodoantipyrine technique in freely moving rats.

The postnatal changes in local cerebral blood flow in freely moving rats were measured by means of the quantitative autoradiographic [14C]iodoantipyrine method. The animals were studied at 10, 14, 17, 21 and 35 days and at the adult stage. At 10 days after birth, rates of blood flow were very low and quite homogeneous in most cerebral structures except in a few posterior areas. From these relatively uniform levels, values of local cerebral blood flow rose notably to reach a peak at 17 days in all brain regions studied. Rates of blood flow decreased between 17 and 21 days after birth and then increased from weaning time to reach the known characteristic distribution of the adult rat. The postnatal evolution of local cerebral blood in the rat is in good agreement with previous studies in other species such as dog and humans that also show higher rates of cerebral blood flow and glucose utilization at immature stages. However, in the rat, local cerebral blood flow and local cerebral glucose utilization are not coupled over the whole postnatal period studied, since blood flow rates reach peak values at 17 days whereas glucose utilization remains still quite low at that stage. The high rate of cerebral blood flow in the 17-day-old rat may reflect the energetic and biosynthetic needs of the actively developing brain that are completed by the summation of glucose and ketone body utilization.

Aging↗

PubMed1988

Comparative effects of caffeine and L-phenylisopropyladenosine on local cerebral glucose utilization in the rat.

The quantitative [14C]2-deoxyglucose autoradiographic method was used to study the effects of the acute administration of 10 mg/kg of caffeine and 0.1 mg/kg of L-phenylisopropyladenosine (LPIA) given separately or in combination. After an injection of caffeine, the local cerebral metabolic rates for glucose (LCMRglu) were increased in 34 out of 61 structures studied, mainly in monoaminergic cell groupings, the thalamus and structures belonging to the extrapyramidal motor system. The administration of LPIA decreased the LCMRglu in 30 out of 61 structures studied. These areas were essentially monoaminergic cell groupings, structures of the extrapyramidal motor system and all hypothalamic areas. After a combined injection of caffeine and LPIA, the LCMRglu was either increased or not changed in structures affected by caffeine or LPIA given alone. The results of the present study indicate that, even if caffeine and LPIA compete for the occupation of adenosine receptors, the effects of these two substances on the energy metabolism of the brain are partly mediated by peripheral mechanisms.

Adenosine↗

PubMed1988

Cerebral glucose utilization after administration of apamin, a toxin active on Ca2+-dependent K+ channels.

The quantitative 2-[14C]deoxyglucose autoradiographic technique was used to examine the effects of acute intravenous administration of apamin, a bee venom toxin specific for one class of Ca2+-dependent K+ channels on brain energy metabolism. With doses of 0.5 mg/kg, the effects of apamin on local cerebral glucose utilization (LCGU) were limited to the habenulo-interpeduncular tract and the interpeduncular nucleus. After a 1.0 mg/kg dose, significant increases in rates of energy metabolism were additionally seen in two other limbic structures, the medial habenula and the lacunosum molecular of Ammon's horn as well as in the auditory cortex. Thirty minutes after the injection of 2 mg/kg apamin, LCGU was significantly decreased in the frontoparietal motor area, globus pallidus and accumbens nucleus. Ninety minutes after 2 mg/kg of the toxin, the average glucose utilization of the brain as a whole was enhanced by 35%, and rates of energy metabolism were significantly increased in 50 out of the 75 areas examined. The effects of apamin on cerebral glucose utilization are not totally related to the distribution of apamin binding sites. However, high densities of apamin binding sites are found in the habenulo-interpeduncular tract and the interpeduncular nucleus, the limbic areas that are highly affected by the toxin at the LCGU level.

Animals↗

PubMed1988

Local cerebral glucose utilization in controlled graded levels of hyperglycemia in the conscious rat.

Local cerebral glucose utilization assayed by the [14C]deoxyglucose ([14C]DG) method and calculated by means of its operational equation with values for the rate constants and lumped constant determined in rats under physiological conditions remains relatively stable with variations in arterial plasma glucose concentration within the normoglycemic range. Large changes in arterial plasma glucose level may, however, significantly alter the values of these constants and lead to artifactual results. Values for the lumped constant have been measured and reported for a wide range of arterial plasma glucose concentrations ranging from hypoglycemia to hyperglycemia in the rat (Schuier et al., 1981; Suda et al., 1981; Pettigrew et al., 1983). In the present study we have redetermined the rate constants in rats with arterial plasma glucose levels clamped at approximately 350, 450, and 550 mg/dl (i.e., 19, 25, and 31 mM) by a glucose clamp technique. The rate constants for the transport of DG from plasma to brain, K1*, and its phosphorylation in tissue, k3*, were found to decline with increasing plasma glucose levels, while the rate constant for its transport back from brain to plasma, k*2, remained relatively unchanged from its value in normoglycemia. These rate constants were used together with the previously determined values for the lumped constants to calculate local rates of cerebral glucose utilization in three groups of rats in which arterial plasma glucose levels were clamped at approximately 350, 450, and 550 mg/dl (i.e., 19, 25, and 31 mM). Average glucose utilization in the brain as a whole was unchanged in hyperglycemia from the values calculated in normoglycemic rats with the standard normal set of constants. Changes in the rate of glucose utilization were found, however, in the hypothalamus, globus pallidus, and amygdala during hyperglycemia.

Animals↗

PubMed1988

Quantitative autoradiographic measurement of local cerebral glucose utilization in freely moving rats during postnatal development.

The quantitative 2-14C-deoxyglucose autoradiographic method of Sokoloff et al. (1977) was used to measure local cerebral glucose utilization in freely moving developing rats. The animals were studied at 10, 14, 17, 21, and 35 d and at the adult stage. Glucose utilization was very low and quite uniform in 10- and 14-d-old rats, ranging from 20 to 30 mumol/100 gm/min, except in a few posterior areas. Between these 2 stages, rates of glucose utilization significantly increased in 6 areas, among which 4 were belonging to the auditory system. Between 14 and 17 d, glucose utilization significantly changed in 9 structures out of the 68 studied, mainly auditory, visual, parietal, and thalamic areas. Between the stages of 17 and 21 d, glucose utilization was increased by 50 or 100% in all brain structures studied, except in the medial habenula and white matter areas. After weaning time, rates of glucose utilization still significantly changed in 50 areas, widely distributed through all studied systems. Between 35 d and the adult stage, the average rate of glucose utilization did not change and rates of energy metabolism significantly increased in 13 brain areas. In one structure, the medial habenula, glucose utilization was already high 10 d after birth and did not change over the whole studied period. These increases in the rates of glucose utilization are consistent with the behavioral, anatomical, and functional changes known to occur during this period of development in the rat.

Aging↗

PubMed1987

Effects of early chronic phenobarbital treatment on the maturation of energy metabolism in the developing rat brain. I. Incorporation of glucose carbon into amino acids.

The influence of phenobarbital (PhB) on the utilization of glucose by the cerebral cortex and the cerebellum was studied in rats during postnatal development. The animals were treated from day 2 to day 35 after birth by a daily injection of 50 mg/kg PhB or by saline. The rats were studied at 5 postnatal stages: 7, 10, 14, 21 and 35 days. PhB treatment induced a 10% decrease in body and brain weight over the whole period studied and a transient significant decrease in circulating thyroxin levels at 14 days after birth. Amino acid levels in the cerebral cortex and particularly in the cerebellum were not greatly affected by the pharmacological treatment. The conversion of [2-14C]glucose into amino acids was significantly decreased in both cerebral structures between day 7 and day 14 after birth. The distribution of radioactivity between amino acids was not affected in the cerebral cortex but was significantly changed by PhB treatment in the cerebellum. Specific radioactivity values of amino acids were lower in PhB- than in saline-treated animals in both studied structures. The results of the present study show that glucose utilization is reduced in the brain of PhB-treated animals as compared to the controls and that the cerebellum seems to be more affected than the cerebral cortex.

Aging↗

PubMed1987

Effects of early chronic phenobarbital treatment on the maturation of energy metabolism in the developing rat brain. II. Incorporation of beta-hydroxybutyrate into amino acids.

The influence of phenobarbital (PhB) on the utilization of beta-hydroxybutyrate by the cerebral cortex and the cerebellum was studied in rats during postnatal maturation. The animals were treated from day 2 to day 35 after birth either by a daily injection of 50 mg/kg PhB or by saline. The rats were studied at 5 postnatal stages: 7, 10, 14, 21 and 35 days. Plasma beta-hydroxybutyrate and acetoacetate levels reached their peak values between 10 and 14 days after birth. The concentration of both ketone bodies was significantly higher in PhB- than in saline-treated rats between 10 and 35 days after birth. The total incorporation of [3-14C]beta-hydroxybutyrate into amino acids reached a peak value at 14 days after birth and was down to very low values at 35 days. It was higher in PhB- than in saline-treated rats. The specific radioactivity values of glutamate, glutamine, aspartate and GABA were significantly higher in PhB- than in saline-treated especially at 10 days after birth. These results demonstrate that a PhB treatment induces an increase in brain ketone body utilization in neonate rats, which is likely to balance the decrease in brain glucose utilization induced by this pharmacological treatment.

3-Hydroxybutyric Acid↗

PubMed1987

Caffeine-diazepam interaction and local cerebral glucose utilization in the conscious rat.

The quantitative 2-[14C]deoxyglucose autoradiographic method was used to study the effects of the acute administration of a sedative anticonvulsant dose of diazepam (2 mg/kg) on rat brain energy metabolism. This benzodiazepine was injected to rats chronically treated for two weeks either by caffeine (10 mg/kg/day) or by saline. After the administration of diazepam to saline-treated rats, average glucose utilization of the brain as a whole was reduced by 21% and rates of glucose utilization were deeply decreased in frontal and auditory cortex, mammillary body, lateral thalamus, medial and lateral geniculate. In caffeine-treated rats, the administration of diazepam induced the same effects of brain energy metabolism as in saline-treated rats. The results of the present study indicate that diazepam mainly decreases glucose utilization in structures widely believed to mediate anxiety.

Animals↗

PubMed1987

Glucose and amino acid metabolism in chick telencephalon slices: changes with incubation conditions and animals' development.

Glucose and amino acid metabolism in 1- and 30-day-old chick telencephalon slices was studied in two incubation media in the presence or in the absence of a continuous oxygenation. Medium 1 has a composition and a tonicity similar to cerebrospinal fluid, medium 2 is hypertonic and does not contain any K+ ions. The incorporation of glucose carbon into amino acids and the distribution of radioactivity between the different amino acids are close to the ones observed in the chick brain in vivo only when the slices are incubated in medium 1, with oxygen at 30 days and without oxygen for the 1-day-old chick. It also appears that if oxygenation is necessary for incubation of mature brain tissue in vitro, the absence of the medium oxygenation is more suitable for the study of glucose metabolism in 1-day-old chick brain slices.

Aging↗

PubMed1987

Effects of insulin on local cerebral glucose utilization in the rat.

The effects of hyperinsulinemia on local cerebral glucose utilization were studied by the quantitative autoradiographic 2-[14C]deoxyglucose method in normal conscious rats under steady-state normoglycemic conditions. Hyperinsulinemia and a steady state of normoglycemia were achieved and maintained during the experimental period by a continuous intravenous (i.v.) infusion of insulin given simultaneously with a programmed i.v. infusion of D-glucose. Hyperinsulinemia under normoglycemic conditions did not change the average rate of glucose utilization in the brain as a whole, but significant increases in local glucose utilization were found selectively in the ventromedial, dorsomedial, and anterior hypothalamic nuclei. The results suggest that a known anatomical pathway linking the dorsomedial and anterior nuclei with the ventromedial nucleus of the hypothalamus may be physiologically activated in response to hyperinsulinemia.

Animals↗

PubMed1987

Effects of insulin on hexose transport across blood-brain barrier in normoglycemia.

The effects of insulin on 3-O-[14C]methylglucose transport across the blood-brain barrier (BBB) were studied in conscious rats under steady-state normoglycemic conditions. The [14C]methylglucose was infused intravenously at a constant rate, and animals were killed at various times between 5 and 30 min after the initiation of the infusion. The time course of the arterial plasma concentration of [14C]methylglucose was determined in timed arterial blood samples taken during the infusion. Local cerebral tissue concentrations of [14C]methylglucose at the time of killing were determined by quantitative autoradiography of brain sections. The rate constants for inward and outward transport of [14C]methylglucose across the BBB, K1, and k2, respectively, were estimated by a least-squares, best-fit of a kinetic equation to the measured time courses of plasma and tissue concentrations. K1 and k2 were reduced by an average of 24 and 31%, respectively, in gray matter and 7 and 16% in white matter from values estimated similarly in normal insulinemic control rats. The equilibrium distribution ratio, K1/k2, for [14C]methylglucose in brain increased by approximately 10-11% in the hyperinsulinemic animals. Because 3-O-[14C]methylglucose shares the same carrier that transports glucose and other hexoses across the BBB, these results suggest that hyperinsulinemia decreases the rate constants for transport but increases the distribution space for hexoses in brain. These effects are, however, quite small and are probably minor or negligible when compared with the major effects of insulin in other tissues.

3-O-Methylglucose↗

PubMed1986

Comparative effects of acute and chronic administration of caffeine on local cerebral glucose utilization in the conscious rat.

The quantitative 2-[14C]deoxyglucose autoradiographic method was used to compare the effects of acute and chronic administration of caffeine on rat brain energy metabolism. The acute intravenous administration of caffeine (10 mg/kg) to naive rats induced widespread increases in glucose utilization in 20 of 62 structures, mainly in striatal and related areas as well as in the 2 raphe nuclei and the locus coeruleus. After 2 weeks' chronic intraperitoneal injection of caffeine (10 mg/kg), increases in glucose utilization were seen in 6 of 62 structures: the substantia nigra, pars compacta, dorsal raphe, locus coeruleus and the 3 parts of the caudate nucleus. An acute caffeine injection (10 mg/kg) to these chronically caffeine-treated rats induced a further increase in glucose utilization in 9 additional structures but there was no significant difference in the effects of an acute administration of caffeine whether the rats had been chronically pretreated with caffeine or saline. The results of the present study show that brain energy metabolism seems to be subject to only partial tolerance to central stimulation by caffeine.

Animals↗

PubMed1986

Ambient temperature and ketone body plasma concentration in fasting geese.

The effect on ketonemia of alternate exposure to ambient temperatures (Ta) of 25 and 5 degrees C was investigated in fasting geese. Three experimental birds were compared to three controls continuously exposed to 25 degrees C Ta while fasting. During the first 9 days of fasting, when both groups were exposed to 25 degrees C, plasma concentration of beta-hydroxybutyrate (beta-OHB) increased similarly in both, from 0.10 +/- 0.02 to 6.62 +/- 0.71 mmol X L-1. It later plateaued at 8-9 mmol X L-1 in the control birds. When the experimental birds were exposed to 5 degrees C Ta between the 9th and 15th day of the fast, it increased further during the first 24 h but thereafter decreased of 57%, from 8.62 +/- 1.56 to 3.73 +/- 1.24 mmol X L-1. This decrease was reversed within the 6 days of return to 25 degrees C Ta. In both groups, plasma acetoacetate (AcAc) concentration remained very low during the fast: 51 +/- 1 mumol X L-1. This reversible cold-induced effect on ketonemia may be used for investigating the possible role of ketone bodies in protein sparing during fasting.

3-Hydroxybutyric Acid↗

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↗