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At least 811 records · Page 45Linked to original sources
PubMed1990

Measures of gender differences in the human brain and their relationship to brain weight.

A series of gross brain linear measurements and cross-sectional surface areas were obtained in a sample of 69 postmortem adult human brains. Data indicate that a subset of these measurements are sexually dimorphic and can be used to discriminate between male and female brains. Results further suggest that studies on gender differences in neuromorphometry can be greatly enhanced if they account for sample variance in brain weight. Using 19 of the gross brain measures delineated in this study, it is possible to accurately predict brain weight. It is believed that the measures obtained in this study will facilitate expanded correlative studies of brain morphology and neuropsychological profiles using either postmortem material or in vivo magnetic resonance imaging scans.

Brain↗
PubMed1978

Identification and characterization of a brain-specific antigen enriched in neonatal brain. I. Developmental, regional distribution and molecular weight studies.

An antiserum raised to the 20--40% ammonium sulfate cut of the soluble proteins extracted from whole neonatal rat brain has been absorbed with liver affinity columns. The absorbed antiserum recognizes a high molecular weight antigen(s) that is (i) restricted to nervous tissue, (ii) enriched in neonatal rat brain, and (iii) present from the 17th day of gestation throughout adult life. The name given to this brain-specific antigen(s) is NABSA, short for 'neonatal-associated brain-specific antigen'. NABSA is immunologically unrelated to S-100 or 14-3-2. NABSA levels in whole rat brain increased soon after birth. The specific activity of NABSA at 2--3 days postpartum reached 3--5-fold higher levels than are found in adult brain. NABSA declined to adult levels by the 10th postnatal day, well before CNS maturation was complete. Regional variations in NABSA levels were found in the rat neonate; highest activities occurred in neonatal cerebellum. Similar variations were observed in adult brain.

Age Factors↗
PubMed1980

Polarity of the blood-brain barrier: distribution of enzymes between the luminal and antiluminal membranes of brain capillary endothelial cells.

The subcellular distribution in brain capillaries of alkaline phosphatase and Na+, K+-ATPase was investigated by two methods. Cytochemical studies using whole brain perfusion and electron microscopic examination indicated that alkaline phosphatase activity was located in both the luminal and antiluminal cytoplasmic membranes of the brain capillary endothelial cells. By contrast, the K+-dependent phosphatase activity associated with Na+, K+-ATPase was located in only the antiluminal membrane. Biochemical studies using membranes prepared by homogenization of isolated brain capillaries and density gradient centrifugation resulted in identification of two plasma membrane fractions. The light fraction contained alkaline phosphatase but very little Na+, K+-ATPase while the heavier fraction contained both enzyme activities. In addition, gamma-glutamyl transpeptidase showed a distribution similar to alkaline phosphatase while 5'-nucleotidase activity was distributed with the Na+, K+-ATPase activity. We conclude that the luminal and antiluminal membranes of brain capillaries are biochemically and functionally different. This polarity should permit active solute transport across brain capillary endothelial cells which are the cells responsible for the blood-brain barrier.

Alkaline Phosphatase↗
PubMed1993

Assessing chronic brain damage by quantification of regional volumes in postischemic rat brains.

The present study provides data on fresh volumes of 39 anatomically defined brain regions after a 10 min transient forebrain ischemia in the rat. Ischemia was induced by occlusion of the carotid arteries and simultaneous hypotension. After a survival period of 3 months the rats were transcardially perfusion-fixed with Bodian's solution, and the brains processed for paraffin embedding and serially sectioned. The sections were Nissl-stained for delineation of the brain regions. The volume of a brain region was calculated from 8-10 equidistant sections, using the Cavalieri method and corrected for shrinkage of the brain. Fresh volumes were reduced by 27-50% in the layers of the hippocampal CA1 sector, by 40-46% in the substantia nigra, by 19% in the caudate nucleus, by 13% in the subiculum and the cingulate areas 1-3, by 12-14% in the retrosplenial and temporal areas. The results show that determination of fresh volumes is a sensitive method for quantification and localization of ischemic brain damage in the whole brain.

Animals↗
PubMed1986

Effect of mealing on plasma and brain amino acid, and brain monoamine in rats after oral aspartame.

Aspartame (APM; L-aspartyl-L-phenylalanine methyl ester) was investigated for its ability to alter brain amino acids and monoamines in overnight fasted rats allowed to consume commercial diets for 60 minutes. In addition, the effects of mealing on the changes in plasma and brain amino acids and brain monoamines induced by glucose and/or insulin, and known pharmacologically active compounds, were studied. The consumption of the commercial chow largely prevented changes in blood glucose and amino acids, and brain amino acids and the monoamines dopamine, norepinephrine and serotonin that might be expected to occur following glucose with or without insulin. Feeding failed to prevent changes in the above parameters when 5-hydroxy-tryptophan, p-chlorophenylalanine and reserpine were administered. The oral administration of up to 250 mg/kg BW APM with water or glucose followed by free feeding failed to alter brain monoamines. These studies demonstrate the potent ability of food to normalize biochemical parameters in blood and brain that otherwise might occur, and clearly show the lack of effect on brain monoamine levels of abuse doses of APM when administered with food.

5-Hydroxytryptophan↗
PubMed1994

Brain growth retardation due to the expression of human insulin like growth factor binding protein-1 in transgenic mice: an in vivo model for the analysis of igf function in the brain.

Three lines of transgenic (Tg) mice carrying a fusion gene linking the mouse metallothionein-I promoter to a cDNA encoding human insulin-like growth factor binding protein-1 (hIGFBP-1) were found to express the transgene in brain. As judged by comparing Tg brain weights to those of non-transgenic littermates, adult hemizygotic Tg mice of each line exhibited brain growth retardation (16.2%, 14.4% and 8.1% reductions in weight, respectively in each line). In two lines, total brain DNA and protein content were decreased. Further analysis indicated that the brain growth retardation was manifested in the second week of postnatal life. Given that the insulin-like growth factors (IGFs) stimulate cell proliferation and/or survival in neural cultures and that hIGFBP-1, when present in a molar excess, inhibits IGF interactions with their cell surface receptors, the brain growth retardation in hIGFBP-1 Tg mice likely results from hIGFBP-1 inhibition of IGF-stimulated growth-promoting actions. These hIGFBP-1 Tg mice should prove useful in defining IGF actions during postnatal brain maturation.

Aging↗
PubMed1986

Patterns of gene expression in the murine brain revealed by in situ hybridization of brain-specific mRNAs.

Biochemical differences between neuronal cell populations of the mammalian brain, including selection of neurotransmitters and distinct neural antigens, suggest that the regulation of gene expression plays an important role in defining brain function. Here we describe the use of in situ hybridization to identify cDNA clones of highly regulated mRNA species and to define directly their pattern of gene expression in brain at both gross morphological and cellular levels. One of the selected cDNA clones, pMuBr2, detected a single 3.0 kb mRNA species, which from in situ hybridization appears specific to oligodendroglia cells. Three other cDNA clones, pMuBr3, 8 and 85, identified polyadenylated mRNA transcripts expressed by neuronal cells of the murine brain. Viewed at the gross morphological level, the mRNAs hybridizing to these cDNA sequences exhibit different patterns of abundance distinguishing such brain structures as pons, anterior thalamus, hippocampus, basal ganglia and anterior lobe of the neuroendocrine pituitary gland. At the cellular level, in situ hybridization revealed that these mRNAs are differentially expressed by morphologically and functionally distinct neurons of the cerebellum and hippocampal formation. When examined in the context of known brain function, however, the regulated expression of the neuron-specific mRNAs does not correlate simply with known cellular morphology or previously demonstrated neuronal relationships suggesting novel patterns of gene expression which may contribute to brain function.

Animals↗
PubMed1989

Molecular cloning and nucleotide sequence of rat brain argininosuccinate lyase cDNA with an extremely long 5'-untranslated sequence: evidence for the identity of the brain and liver enzymes.

Argininosuccinate lyase (EC 4.3.2.1) is an enzyme present in the brain of ureotelic animals. Using as a probe rat liver argininosuccinate lyase cDNA, already isolated and sequenced (Amaya, Y., Matsubasa, T., Takiguchi, M., Kobayashi, K., Saheki, T., Kawamoto, S. and Mori, M., J. Biochem., 103 (1988) 177-181), we screened a rat brain cDNA library constructed in the lambda gt11 expression vector and obtained a single cDNA clone. This cDNA clone contained an open reading frame encoding a polypeptide of 461 amino acid residues (predicted Mr = 51,390), a 5'-untranslated sequence of 967 bp and a 3'-untranslated sequence of 74 bp. The length of the 5'-non-coding region of the cDNA seems to be one of the longest among the cDNAs heretofore isolated. A comparison of the brain cDNA sequence (2424 bp) with the corresponding region of the liver cDNA (1574 bp) revealed differences in 5 nucleotides. The brain clone contained A----G and C----G base differences from the hepatic sequence, resulting in amino acid changes from Tyr and Arg in the liver clone, to Cys and Gly in the brain clone, respectively. The other 3 nucleotide differences are silent with respect to the amino acid sequence of the protein. Therefore, the amino acid sequence of the brain argininosuccinate lyase, as deduced from the nucleotide sequence of its cDNA clone, was identical with that of the liver protein, except for two amino acid residues. These minor changes may reflect a microheterogeneity of the argininosuccinate lyase gene. The brain and liver enzymes seem to be encoded by the same structural gene.

Amino Acid Sequence↗
PubMed1994

Free radical scavenging by brain homogenate: implication to free radical damage and antioxidant defense in brain.

To study the mechanisms of free radical-induced brain damage and the antioxidant defense in the brain, we quantified the superoxide and hydroxyl radical scavenging effects of brain homogenate using electron spin resonance spectrometry. Brain homogenate was found to scavenge both superoxide and hydroxyl radicals in concentration-dependent fashion. Heat denaturation significantly decreased these scavenging effects. The ability of brain homogenate to scavenge free radicals implies that brain damage can be induced by free radicals since they are known to react virtually with any type of molecule such as nucleic acids, membrane lipids, and proteins in the brain. On the other hand, some molecules which can be regenerated or repaired after free radical scavenging are considered to be antioxidants which include both enzymatic and non-enzymatic antioxidants. Measurement of the decrease in antioxidant activity following heat denaturation suggests that the contribution of enzymatic antioxidants is about 20-40% in scavenging superoxide radicals and about 10-20% in scavenging hydroxyl radicals.

Animals↗
PubMed1988

The patterns of [14C]2-deoxyglucose uptake in female rat brain produced by electrical stimulation of hypothalamic and limbic brain areas.

The aim of this study was to investigate the pattern of [14C]2-deoxyglucose uptake in anaesthetized rat brain produced by electrical stimulation of brain areas implicated, by previous electrical stimulation studies, in the neural control of pituitary hormone and especially gonadotrophin secretion. Stimulation of the median eminence led to a significant increase in the relative metabolic activities of the arcuate, ventromedial hypothalamic, supraoptic and paraventricular nuclei and the preoptic area. Stimulation of the suprachiasmatic or paraventricular nuclei or the medial preoptic area, anterior hypothalamic area, the dorsal or ventral hippocampus or amygdala led to an increase in the relative metabolic activity of many brain regions known to have direct connections with these areas, but in addition produced increases in the relative metabolic activity of areas which have secondary connections. Hippocampal stimulation confirmed previous neuroanatomical findings of major intrinsic functional connections between different fields of the ipsilateral and contralateral hippocampus. Stimulation of the amygdala, unexpectedly, did not change the relative metabolic activity of the arcuate nucleus and medial preoptic area which have neuroanatomical connections with the amygdala. Similarly, stimulation of the medial preoptic area did not change significantly the relative metabolic activity of the mamillary body and dorsomedial thalamic area. The effect of preoptic area stimulation on the relative metabolic activity of several brain regions was changed by ovariectomy and by injection of oestradiol benzoate. Stimulation of the preoptic area and suprachiasmatic nuclei, but not the anterior hypothalamic area or other brain regions, increased significantly the plasma concentrations of luteinizing hormone. These results show that (i) electrical stimulation of brain areas concerned with the control of gonadotrophin and other pituitary hormone secretion changes the metabolic activity of nuclei and neural pathways extrinsic as well as intrinsic to the hypothalamic-pituitary system, (ii) the [14C]2-deoxyglucose method can detect changes in antidromic as well as orthodromic activity and in multi-synaptic pathways, (iii) neuroanatomical pathways are not always activated metabolically by electrical stimulation, and (iv) the preoptic-suprachiasmatic nucleus gonadotrophin control system is discrete and is little affected by increased metabolic activity of the hypothalamus produced by stimulation of the anterior hypothalamic area or other brain areas.

Animals↗
PubMed1990

MK-801 pretreatment enhances N-methyl-D-aspartate-mediated brain injury and increases brain N-methyl-D-aspartate recognition site binding in rats.

Direct intracerebral administration of N-methyl-D-aspartate typically produces focal brain injury. (+)-5-Methyl-10,11-dihydro-5H-dibenzo[a,d]cyclohepten-5,10-immi ne maleate (MK-801), a non-competitive N-methyl-D-aspartate antagonist, can protect against N-methyl-D-aspartate-mediated brain injury when administered shortly before or after an intracerebral injection of N-methyl-D-aspartate. However, in this study we report that in perinatal rats if MK-801 (1 mg/kg) is administered intraperitoneally 24 h prior to a unilateral intrastriatal N-methyl-D-aspartate injection, N-methyl-D-aspartate-mediated brain injury is paradoxically enhanced. The severity of resulting brain injury is 15-25% greater in groups that received MK-801 in comparison with saline-treated controls (P less than 0.001, linear regression analysis). In contrast, the severity of brain injury resulting from intrastriatal injection of the glutamate agonist quisqualate is not altered by a similar 24 h MK-801 pretreatment. Furthermore, the enhanced toxicity of N-methyl-D-aspartate produced by a 24 h pretreatment with MK-801 is completely blocked if a second dose of MK-801 is administered 15 min after the intrastriatal injection of N-methyl-D-aspartate. To determine if MK-801 produced alterations in glutamate receptor pharmacology co-incident with the enhanced toxicity of N-methyl-D-aspartate, in vitro quantitative autoradiography for excitatory amino acid receptor subtypes was performed with [3H]glutamate and [3H]N-1-(2-thienyl)cyclohexyl-3,4-piperidine in seven-day-old rats killed 2 or 24 h after MK-801 (1 mg/kg) administration. A 2 h MK-801 pretreatment produced a 30-50% increase in [3H]glutamate binding at N-methyl-D-aspartate preferring recognition sites in all four brain regions examined (areas CA1 and CA3 of the hippocampus, corpus striatum, cingulate cortex) in comparison with saline-treated controls (P less than 0.05, ANOVA). [3H]N-1-(2-Thienyl)cyclohexyl-3,4-piperidine binding to the phencyclidine site associated with the N-methyl-D-aspartate receptor was reduced by 60-80% in all brain regions examined (P less than 0.001). Quisqualate-sensitive [3H]glutamate binding was not altered by a 2 h MK-801 pretreatment. In animals that received a 24 h MK-801 pretreatment.(ABSTRACT TRUNCATED AT 400 WORDS)

Animals↗
PubMed1986

Effects of maternal nicotine injections on brain development in the rat: ornithine decarboxylase activity, nucleic acids and proteins in discrete brain regions.

Fetal exposure to nicotine via maternal cigarette smoking produces intrauterine growth retardation and postnatal behavioral abnormalities. In this study, biochemical characteristics of brain development were compared in normal rats and in rats whose mothers received chronic nicotine injections throughout pregnancy. Nicotine exposure produced a persistent elevation of fetal ornithine decarboxylase activity preferentially in brain; in keeping with this selectivity, there was no evidence of the sparing of brain growth which ordinarily accompanies non-specific toxic insult. After birth, DNA synthesis was suppressed throughout the brain and there was a subsequent rebound during the phase of "catch-up" growth. Evidence was also obtained for regional selectivity of the adverse effects of maternal nicotine injections: the effects on DNA synthesis and levels were most profound in cerebellum (a region which matures postnatally) and growth-impairment was least evident in midbrain & brainstem, an early-maturing region. The maternal nicotine group also displayed desynchronization of the ontogenetic patterns of DNA, RNA and proteins in every brain region. These data indicate that maternally-injected nicotine compromises early biochemical events which delineate brain cell replication and differentiation; these alterations are eventually translated into abnormalities in development of specific brain regions.

Animals↗
PubMed1992

Nocardia as a pathogen of the brain: mechanisms of interactions in the murine brain--a review.

Nocardia asteroides strain GUH-2 invades the brain without inducing an early inflammatory response in normal mice. This strain can grow within the neurons as well as adjacent areas causing neurological damage without abscess formation. At low inoculum doses, this organism is gradually cleared from the brain after the initial burst of growth. Therefore, at two weeks, the brains of these mice appear to become sterile, but the animals begin to develop a variety of neurological signs including an L-dopa responsive headshake. It was found that mice that recovered from sublethal infection with N. asteroides strain GUH-2 had progressive and permanent neuron damage in regions of the brain, the extent of which appeared to correlate with specific neurological signs. The mechanisms of this response are not known, but current data indicate that the level of nonspecific phagocyte activation (microglia?) within the brain represents an important first line of defense. Next, T-lymphocytes are important in the secondary response in the brain to nocardial invasion. Finally, B-lymphocytes and a humoral immune response may be involved in these complex interactions; however, it is not clear how these responses relate to the permanent and progressive brain damage induced by Nocardia. It is possible that these latter responses may exacerbate neurodegeneration.

Animals↗
PubMed1991

Reversed-phase high-performance liquid chromatography method for the determination of bemegride in serum and brain tissue: pharmacokinetics and brain distribution of an intraperitoneal subconvulsive dose in rats.

A simple and rapid HPLC method has been developed for the quantification of bemegride in serum and brain tissue, using p-methylphenobarbital as an internal standard. Serum and brain tissue homogenate samples were extracted with ethyl acetate and the evaporated and redissolved extracts injected into a reversed-phase column. The compounds were eluted with an acetonitrile-phosphate buffer mixture and monitored at 200 nm. A linear response was obtained in the range 1-40 micrograms ml-1 for serum and 1-40 micrograms g-1 for brain tissue. Within-day and between-day precisions were less than 5% and the analytical recovery greater than 76.4%. This method has been used to investigate the kinetic profiles of the drug in serum and discrete areas of rat brain after intraperitoneal administration of a subconvulsive dose of bemegride (10 mg kg-1). Peak concentrations occurred in the brain and serum at the same time (30 min), followed by a biphasic decay. The results also indicated the accumulation of the drug in the brain, with no significant differences (p greater than 0.05) in the impregnation of the different brain areas investigated.

Animals↗
PubMed2005

Clinical outcome of hypofractionated conventional conformation radiotherapy for patients with single and no more than three metastatic brain tumors, with noninvasive fixation of the skull without whole brain irradiation.

PURPOSE: To evaluate the efficacy and toxicity of hypofractionated conventional conformation radiotherapy (HCCRT) with noninvasive fixation of the skull on patients with single or several brain metastases. METHODS AND MATERIALS: The subjects were 44 patients who had three or fewer brain metastases (26 solitary, 18 multiple). Treatment was conducted on 65 metastases by rotational conformal beam or multiple fixed coplanar beams with a standard linear accelerator. The planning target volume consisted of the tumor and a 1-cm safety margin. The median isocentric dose was 24 Gy (range, 18-30 Gy) in 3-5 fractions. Whole-brain irradiation was not applied as an initial treatment. RESULTS: Actuarial local tumor control rates at 6 months and 1 year were 78.4% and 71.9%, respectively. In-field recurrence was noted in 10 of 65 tumors, and repeat HCCRT was applied in 5 tumors. Actuarial overall survival rates at 1 year, 2 years, and the median survival time were 50.8%, 24.1%, and 5.8 months, respectively. The patients with an active primary cancer and poor performance status had a poorer prognosis than those without those factors. Actuarial freedom from second brain metastases rates at 6 months, 1 year, and 2 years were 86.6%, 69.0%, and 40.9%, respectively. Second brain metastases were observed in 9 of 44 patients. Lung adenocarcinomas had a higher risk of second brain metastasis than others. Treatment-related severe early or late complications were not observed in this series. CONCLUSIONS: Hypofractionated conventional conformation radiotherapy achieved sufficient tumor control and survival. The results suggest that HCCRT would be one of the alternatives for patients with either solitary or several brain metastases.

Aged↗
PubMed2004

A standardized method for brain-cutting suitable for both stereology and MRI-brain co-registration.

We have developed an agar-embedding method for brain-slicing that minimizes the geometrical distortions which arise from handling and slicing the fixed postmortem brain. To facilitate postmortem brain-magnetic resonance imaging (MRI) co-registration, each hemisphere is processed separately. We embed the fixed brain hemisphere with reference markers in agar. The block containing the brain and markers is sliced at a fixed interval using a rotary slicer. Each slice is photographed with a high-resolution digital camera. The digital images are realigned as a 3-dimensional volume via a control point-based registration method for multi-slice registration. The realigned multiple slices of the reconstructed postmortem hemisphere are then co-registered to corresponding slices of an in vivo reference MRI-volume. We illustrate these postmortem MRI-brain co-registration methods to correlate in vivo T2-weighted MRI hyperintensities in gray and white matter with underlying pathology. For design-based stereology, the volume of interest (VOI) is defined using reproducible anatomical boundaries. This method is suitable for stereologic measures of structures ranging from defined nuclei to whole brain.

Aged↗
PubMed2005

Cognitive aging as an extension of brain development: a model linking learning, brain plasticity, and neurodegeneration.

Differences in cognitive aging rates among mammals suggest that the pace of brain aging is genetically determined. In this work, we investigate the possibility that brain aging is an extension of brain development. It is possible that a subset of developmental mechanisms are extreme cases of antagonistic pleiotropy in that they are necessary for reaching adulthood and yet later cause age-related diseases. We derive a model linking development and brain aging in which childhood events essential for brain development later result in neurodegeneration. The hypothesis presented herein involves brain plasticity in which the same mechanisms that shape the adult phenotype continue at later ages contributing to cognitive dysfunction and eventually dementia. The same genetic program that decreases brain plasticity at early ages to focus our mind to the surrounding environment may continue in adulthood resulting in cognitive aging. Experimental implications for understanding neurodegeneration in this context are also discussed.

Aging↗
PubMed2006

Exposure in fetus of methylazoxymethanol in the rat alters brain neurotrophins' levels and brain cells' proliferation.

Changes during gestation have been shown to induce brain maldevelopment associated with changes in neurotrophins as nerve growth factor (NGF), brain derived neurotrophic factor (BDNF) and neuropsychiatric disorders in humans. A rat model of altered prenatal brain development resembling the onset of schizophrenia has been obtained by administering in fetus methylazoxymethanol (MAM) at gestational day 12 which impairs the growth of limbic pathways between the entorhinal cortex and the hippocampus. Using the MAM model we studied in young rats the brain levels of both NGF/BDNF and their main receptors, TrkA/TrkB, to investigate whether or not changes in neurotrophins could affect the presence of brain BrdU positive cells. We found increased NGF and BDNF protein levels, associated with elevated TrkA and TrkB expression, in the hippocampus, entorhinal cortex, olfactory lobes and subventricular zone (SVZ), brain areas playing a key role in the production and migration of new dividing cells. We also found higher levels of BrdU positive cells in the SVZ and hippocampus but not a significant potentiation in the entorhinal cortex and olfactory lobes. All together the findings indicate that prenatal MAM exposure in young rats may elicit both neurotrophins' elevation and cell proliferation in limbic brain areas.

Analysis of Variance↗