Distribution, uptake and hydrolysis of cholesterol oleate (-1-14C) in brain tissue after its injection in the cerebral ventricles of the conscious cat]

Distribution, uptake and hydrolysys of cholesteryl oleate (-1-14C) in vivo in the cat's brain were investigated. Four hours following intraventricular injection of cholesteryl oleate (-1-14C), about one third of the injected radioactivity was taken up and about 50 % of that radioactive material was hydrolysed by brain tissue. Even more, the labelled material was found in the brain tissue surrounding the cerebral ventricles as well as in the cerebral cortex, but in varying amounts: the smallest amounts were found in the cerebral cortex, while the highest were in the hypothalamus. Radioactive material was also detected in the peripheral venous blood.     

Uptake and esterification of (4-14C) cholesterol after injection into the cerebral ventricles of conscious cats]

The brain tissue had appreciable capacity to take up and to esterify (4-14C) cholesterol from the cats cerebral ventricles. The highest values of radioactive material in the brain tissue were found 30 minutes after intraventricular injection of (4-14C) cholesterol. Thereafter, within a few hours most of the labelled cholesterol disappeared and by the end of 48 h the brain tissue retained only small amounts of it. at the same time, radioactive material was found in the peripheral venous blood, but in very small amounts. The analysis for cholesterol esters showed that about 50 % of (4-14C) cholesterol taken up by the brain tissue had undergone esterification. The rate of esterification of cholesterol within 48 h remained more or less constant, although a significant peak was noted by the end of 24 h.     

The Subcommissural Organ-Liquor Fibre Complex: the Binding of Catecholamines to the Liquor Fibre in Frogs of the Rana esculenta Complex

Tritiated catecholamines were administered to European green frogs by means of injection into the brain cavity. Their fate within the brain was followed autoradiographically. Especially after injection of ³H-noradrenaline, considerable amounts of radioactive material were found closely associated with the liquor fibre (Reissner's fibre; LF) which is produced by the subcommissural organ. In frogs which survived 3 or 12 hours after injection, the association of radioactive material with the LF appeared to be restricted mainly to the cerebral ventricles, whereas in frogs which survived 24 hours, the radioactivity associated with the LF was most abundant well into the central canal of the spinal cord. The results indicate that the LF is able to pick up, from the cerebrospinal fluid, and bind certain catecholaminergic substances (especially noradrenaline, but not dopamine) and/or their metabolites by rather strong binding forces. The attached material is then transported by the LF into the central canal of the spinal cord, with its practically stagnant fluid content. These results confirm data known from the literature. which are indicative of the LF being involved in regulation of the composition of the fluid within the central canal, e.g. by providing this canal with catecholaminergic substances and/or by removing them from it.     

Metabolism of (1-14C)-palmitic acid in the cat's brain]

Following injection into the cerebral ventricles of conscious cats, (1-14C) palmitic acid was rapidly taken up and incorporated into a variety of brain lipids. The peak of uptake of (1-14C) palmitic acid, about 50% of injected radioactive material, into the brain tissue was obtained within the first 24 h following its administration. Thereafter, the radioactivity slowly decreased reaching the least value by the end of the second week. The most heavily labelled lipids were the phospholipids, while the free fatty acids were appreciably labelled. Small percentage of the radioactive material was found in monoglycerides, diglycerides and triglycerides. The least incorporation was into cholesterol esters.     

Regional distribution of gamma-aminobutyric acid (GABA) in brain of the rhesus monkey

—The concentrations of γ-aminobutyric acid (GABA) in twenty different regions of Rhesus monkey brain were studied. The highest levels were found in the substantia nigra, globus pallidus, and hypothalamus. Regions of the cerebral cortex and thalamus contained low amounts and white matter the lowest. Indirect evidence supporting an inhibitory transmitter role for GABA is discussed.     

Distribution of Cholecystokinin-Like Peptides in the Human Brain

Abstract: The regional distribution of cholecystokinin-like immunoreactivity (CCK-LI) in postmortem human brain material has been investigated. CCK-LI was concentrated particularly in the forebrain (all cerebral cortical areas, amygdala, and hippocampus), with smaller amounts in the basal ganglia, hypothalamus, and periventricular grey. Lowest amounts of CCK-LI were found in the thalamus, cerebellum, and spinal cord.     

The hydromechanics of hydrocephalus: Steady-state solutions for cylindrical geometry

Hydrocephalus is a state in which the circulation of cerebrospinal fluid is disturbed. This fluid, produced within the brain at a constant rate, moves through internal cavities in it (ventricles), then exits through passages so that it may be absorbed by the surrounding membranes (meninges). Failure of fluid to move properly through these passages results in the distention of the passages and the ventricles. Ultimately, this distention causes large displacements and distortion of brain tissue as well as an increase of fluid in the extracellular space of the brain (edema). We use a two-phase model of fluid-saturated material to simulate the steady state of the hydrocephalic brain. Analytic solutions for the displacement of brain tissue and the distribution of edema for the annular regions of an idealized cylindrical geometry and small-strain theory are found. The solutions are used for a large-deformation analysis by superposition of the responses obtained for incrementally increasing loading. The effects of structural and hydraulic differences of white and gray brain matter, and the ependymal lining surrounding the venticles, are examined. The results reproduce the characteristic steady-state distribution of edema seen in hydrocephalus, and are compared with experiment.     

Insulin immunohistochemistry of rodent CNS: Apparent species differences but good correlation with radioimmunological data

Summary Using an indirect immunofluorescence technique the distribution of insulin was mapped in brains of Wistar strain rats and mice. Insulin immunoreactivity was found to be widely distributed throughout mouse CNS, whereas in rat brain a restriction of immunoreactive material to cerebral blood vessels and ependymal cells and/or tanycytes of the brain ventricles was observed. In radioimmunological studies the amount of insulin (IRI) was estimated for different brain areas (cerebral cortex, brain stem, cerebellum, hippocampus, thalamus and hypothalamus). In the case of Wistar rats very low levels of IRI were found. On the contrary, the same regions in mouse brain contained considerably greater amounts of IRI. The comparison between histochemical and biochemical data revealed a good correlation. It is concluded that part of the insulin measured by radioimmunoassay is associated with neuronal structures.Research supported by the Ministerium für Hoch- und Fachschulwesen der DDR and Ministerium für Gesundheitswesen der DDR     

Decreased Thalamocortical Functional Connectivity after 36 Hours of Total Sleep Deprivation: Evidence from Resting State fMRI

Objectives

The thalamus and cerebral cortex are connected via topographically organized, reciprocal connections, which hold a key function in segregating internally and externally directed awareness information. Previous task-related studies have revealed altered activities of the thalamus after total sleep deprivation (TSD). However, it is still unclear how TSD impacts on the communication between the thalamus and cerebral cortex. In this study, we examined changes of thalamocortical functional connectivity after 36 hours of total sleep deprivation by using resting state function MRI (fMRI).

Materials and Methods

Fourteen healthy volunteers were recruited and performed fMRI scans before and after 36 hours of TSD. Seed-based functional connectivity analysis was employed and differences of thalamocortical functional connectivity were tested between the rested wakefulness (RW) and TSD conditions.

Results

We found that the right thalamus showed decreased functional connectivity with the right parahippocampal gyrus, right middle temporal gyrus and right superior frontal gyrus in the resting brain after TSD when compared with that after normal sleep. As to the left thalamus, decreased connectivity was found with the right medial frontal gyrus, bilateral middle temporal gyri and left superior frontal gyrus.

Conclusion

These findings suggest disruptive changes of the thalamocortical functional connectivity after TSD, which may lead to the decline of the arousal level and information integration, and subsequently, influence the human cognitive functions.     

SYNTHESIS OF RADIOACTIVE ACETYLCHOLINE FROM [3H]CHOLINE AND ITS RELEASE FROM CEREBRAL CORTEX SLICES IN VITRO

Abstract— Guinea pig cerebral cortex slices were incubated for 60 min in a medium containing [³H]choline with or without the addition of 33 mM-KCl for the last 30 min. KC1 caused the release into the medium of large amounts of both bioassayable and radioactive ACh, while at the same time their concentrations in the tissue decreased. The specific activity (d.p.m./pmol) of the ACh released by KC1 was greater than that released in control incubations, indicating that it comes from a newly synthesized, more radioactive store. The amounts of [³H]choline, [³H]ACh and the specific activity of tissue acetylcholine reached a plateau in the tissue 30 min after the addition of isotope. However isotopic equilibrium was not achieved because the specific activity of the ACh released, with or without KC1 in the subsequent 30 min, was less than the specific activity of the ACh remaining in the tissue. This implies the existence of a pool of ACh in the tissue which is turning over very slowly or is being synthesized from a less radioactive pool of choline. This pool of ACh does not contribute substantially to that released by KC1. Levorphanol at 10⁻³ M, as well as the analgesically inactive stereoisomer, dextrorphan, blocked the KCl-stimulated release of both bioassayable and radioactive ACh. These drugs demonstrate the coupling of synthesis and release of ACh in cerebral cortex slices.     

Lateral differences in GABA binding sites in rat brain

An asymmetric distribution of GABA binding sites was found in the cerebral cortex, hippocampus, cerebellar hemispheres, striatum, and thalamus. Higher levels of [³H]GABA binding were observed in the left-side of most brain areas and in a greater percentage of adult rats, but the opposite asymmetry was found in the thalamus. A similar left-right difference in cerebral hemispheres was also found in five day-old rats, suggesting the genetic predetermination of asymmetry.     

Regional cerebral blood flow changes during hypothermia

1. 1. When brain temperature was decreased from 38 to 22 °C using selective hypothermia, tissue blood flow decreased significantly in cerebral cortex, cerebellum, and thalamus, but did not significantly change in hypothalamic or brain stem tissue.

2. 2. A further decrease in brain temperature to 8 °C produced an increase in blood flow in all tissues except cerebral cortex compared to tissue blood flow measured at 22 °C. Compared to normothermic values, blood flow remained significantly decreased at 8 °C in cerebral and cerebellar cortex and was increased in brain stem.

3. 3. After rewarming, tissue blood flow returned to original baseline values in all tissues except cerebral cortex where blood flow was slightly but significantly decreased and brain stem, where blood flow was increased.

4. 4. These results indicate that the cerebrovascular effects of selective brain cooling are regionally specific. These changes appear to be due to both direct and indirect effects of cerebral hypothermia since brain tissue blood flow changes are apparent, compared to control values, after rewarming of the brain.

     

RNA synthesis in different regions of rat brain at various time intervals after cerebellectomy

RNA synthesis was studied in cerebral cortex, thalamus and brain stem of rat, on the 3rd, 8th, 30th and 75th day after cerebellectomy. An increased RNA synthesis was detected in thalamus at the 30th day and in cerebral cortex and brain stem at the 75th day after cerebellectomy. Our findings suggest that motor compensation following the cerebellectomy could be supported by a spatio-temporal organization of macromolecular synthesis in different brain regions.     

Homotopic transplant of fetal cortex to lesioned motor cortex of adult rats. A comportamental and anatomical study.

Previous investigations have shown that the transplant of fetal nervous tissue in adult, formerly injured, brain induces an improvement of the neurological deficits. The process underlying this finding is not yet known. It has been proposed that this process is favourably supported by the reconstruction of the damaged circuitry, replacing the injured neurons with the transplanted fetal cells. In the present study we have investigated the relation between the improvement of the neurological deficits and the anatomical integration of the transplanted neurons within the host brain. The plan of the investigation included two steps: the first step consisted of inducing neurological deficits by kainic acid lesion of the motor cortex and then studying the changes in the motor learning following a homotopic transplant of fetal cortex in the side of the lesion. The second step consisted of studying the anatomical integration of the transplanted cortex with the thalamus of the host. The results showed that the rats with injury of the motor cortex followed by solid transplant of fetal cortex (E 17) had a significantly greater recovery of the motor learning with respect to non-transplanted rats with a lesioned motor cortex. In the same rats, the connections between the transplanted cerebral cortex and the thalamus of the host has been investigated. WGA-HRP solution was injected in the thalamus and both labeled fiber terminals and labeled cells were searched for in the transplants. The results showed that: 1) the host thalamus projects to the transplanted cortex with a lower density than to the host cortex surrounding the transplant; 2) the thalamic projection to the host cortex is topographically organized, whereas the projection to the transplant is arranged in patches without any topographical organization; 3) the transplant does not send a significant projection to the thalamus of the host. In conclusion, the experimental findings demonstrate that the reconstruction of an injured thalamo-cortical circuitry of adult rats transplanting fetal neurons is not possible. The improvement of the functional deficits by the transplant of fetal tissue may be referred to aspecific factors enhancing the functional activity of the host cortex undamaged by the initial injury. The identification of the nature of the hypothesized factors requires further investigation.     

Neurochemical Abnormalities in Brains of Renal Failure Patients Treated by Repeated Hemodialysis

We examined autopsied brain from 10 patients with end-stage renal failure who had undergone repeated hemodialysis. Eight had classic symptoms, and two had suggestive symptoms of dialysis encephalopathy. Findings were compared with those in autopsied brain from control adults who had never been hemodialyzed. Mean gamma-aminobutyric acid (GABA) contents were significantly reduced in frontal and occipital cortex, cerebellar cortex, dentate nucleus, caudate nucleus, and medial-dorsal thalamus of the hemodialyzed patients, the reduction being greater than 40% in cerebral cortex and thalamus. Choline acetyltransferase activity was reduced by 25-35% in three cortical regions in the hemodialyzed patients. These two abnormalities were observed in the brain of each hemodialyzed patient, regardless of whether or not the patient died with unequivocal dialysis encephalopathy. Pyridoxal phosphate contents were substantially reduced in brains of the hemodialyzed patients, but metabolites of noradrenaline, 3,4-dihydroxyphenylethylamine (dopamine), and 5-hydroxytryptamine (serotonin) were present in normal amounts. Aluminum levels were abnormally high in frontal cortical gray matter in the hemodialyzed patients. Although this study does not clarify the role played by aluminum toxicity in the pathogenesis of dialysis encephalopathy, the abnormalities we found suggest the need for further neurochemical investigations in this disorder.     

Effect of thyroidectomy on phosphorylative oxidation and RNA synthesis in various regions of the brain in the adult monkey

The subcellular effects of thyroidectomy in selected brain regions of Cynomolgus monkey were analyzed. 20 days after operation the respiratory rates, the activities of succinate cytochrome c reductase, glycerol-3-phosphate dehydrogenase and of oligomycin-sensitive ATPase were decreased in mitochondria isolated from all brain structures. The highest reduction (30%) was found in cerebral cortex and hippocampus. Cerebellar and striatal activities were reduced by about 20%. A smaller decrease (15%) was observed in thalamus. The effects of thyroidectomy on in vitro RNA synthesis were followed in cerebral cortex, cerebellum and thalamus. In the three analyzed regions, the activities of nucleolar and nucleoplasmic RNA polymerases dropped by 40%. Replacement therapy with T4 (2.5 micrograms/kg/day) or T3 (1 microgram/kg/day) administered immediately after thyroidectomy for 20 days, maintained mitochondrial and nuclear activities at normal level.     

Identification with a Monoclonal Antibody of a Phylogenetically Conserved Brain-Specific Determinant on a 130,000 Molecular Weight Glycoprotein of Human Brain

Human brain glycoproteins depleted of Thy-1 antigen were used to immunise Balb/c mice for monoclonal antibody production. The F3-87-8 antibody described in this paper interacts with a determinant present in large amounts on all human brain subregions studied (cerebral cortical grey matter, white matter, caudate, thalamus, dentate nucleus, putamen, cerebellar cortex) but absent from all other tissues examined (liver, heart, kidney, spleen, thymus, lymph node, erythrocyte, adrenal gland, and peripheral nerve). The determinant is conserved in mammalian evolution, as the brains of the rat and dog have amounts equal to that found in human brain. Balb/c mouse brain has approximately one-third as much antigen activity as these other mammalian brains, whereas brains of the frog and chicken have no detectable antigenic activity. Developmental studies showed that 16-week human foetal brain and neonatal dog brain had little or no antigen activity, indicating a dramatic increase in the amount of the determinant with brain maturation. Biochemical studies showed that the F3-87-8-bearing molecule was a major sialoglycoprotein of human brain with an apparent molecular weight of 130,000. It was shown by immunofluorescence to be particularly localised in what appeared to be fibre tracts in the thalamus and basal ganglia, and in the dentate nucleus, although all regions including grey matter were stained.     

Apolipoprotein e deficiency leads to altered brain uptake of alpha tocopherol injected into lateral cerebral ventricles

The incorporation of radioactive alpha tocopherol by various brain regions of wild type and apolipoprotein E (apoE)-deficient mice was investigated. Labeled tocopherol was injected into the lateral cerebral ventricles of 11 weeks old, male mice. Radioactive cholesterol injected simultaneously was used as an internal standard to account for experimental variability. Most areas of the brain of apoE-deficient mice took up less of alpha tocopherol per mg of protein than wild type animals. However, specific activity of alpha tocopherol was higher in cerebellum, pons, hypothalamus, midbrain and cerebral cortex in apoE-deficient brains than the wild type. This could be due to (a) the lower levels of alpha tocopherol in apoE-deficient brain and (b) reductions in the clearance and transport of tocopherol (possibly mediated by apoE). Tocopherol uptake by hippocampus was unusual since it was lower in apoE deficiency whether the data were expressed as specific activity or per mg of protein. Nearly all of the injected alpha tocopherol remained unchanged in the brains of both apoE-deficient and wild type animals suggesting low turnover. Overall, the current data reinforce the hypothesis that apoE is a key protein involved with the transport and/or retention of alpha tocopherol in brain.     

Changes in cerebral level of monoamines by Japanese encephalitis virus infection

The changes in monoamine levels of different brain regions following Japanese encephalitis virus (JEV) intraperitoneal inoculation were examined in experimentally JEV-infected mice. In addition, virus distribution was studied using infectivity assay and immuno-histochemistry of viral antigen. 1) The level of monoamines in brain tissues was not affected by 48 hours after viral inoculation, but marked effects were elicited at 96 hours after the inoculation. The cerebral concentration of 5-hydroxyindole-3-acetic acid (5 HIAA) was increased, while that of dopamine (DA) showed a decrease. Especially these alteration were observed in the cerebral cortex, but not in the cerebellum. 2) The viral growth in the brain was observed at 48 hours after the inoculation. The growth in the cerebellum, however, was found to be lower than those in other cerebral regions. 3) The viral antigen was detected in the cerebral cortex, hippocampus, mesencephalon and diencephalon in addition to the substantia nigra and striatum. From these results, it is presumed that clinical manifestation of JEV infection may involve the changes in the metabolism of neurotransmitter, especially those of DA and serotonin in the brain.