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At least 1,189 records · Page 66Linked to original sources
PubMed1985

Inability of dimethyl sulfoxide to increase brain uptake of water-soluble compounds: implications to chemotherapy for brain tumors.

There is conflicting evidence as to whether dimethyl sulfoxide (DMSO) can reversibly open the blood-brain barrier and augment brain uptake of water-soluble compounds, including anticancer agents. To investigate this, 125I-human serum albumin, horseradish peroxidase, or the anticancer drug melphalan was administered iv to rats or mice, either alone or in combination with DMSO. Some animals received an additional ip priming dose of DMSO. The regional brain concentrations of each substance were measured after the animals were killed. DMSO administration did not significantly increase the brain uptake of any of the compounds as compared to control uptakes. These results do not support prior reports that DMSO increases the permeability of water-soluble agents across the blood-brain barrier.

Animals↗
PubMed1993

[Brain injury and brain disease. Need and importance of early rehabilitation].

Early rehabilitation means rehabilitation which begins during the treatment for acute illness or trauma, immediately after the management of life-threatening conditions and stabilization of vital functions. Early rehabilitation is intended to make extensive use of the regenerative capacities of the brain and prepare effortless transition to further training programs. The necessity of early rehabilitation after severe brain injury or vascular brain disease is now recognized. However the means available now, i.e. trained staff, equipment and buildings, are insufficient. In order to estimate the resources needed the epidemiology of head and brain injury and vascular brain disease in Germany was analyzed by Infratest Gesundheitsforschung, Munich. The study was initiated and supported by the Kuratorium ZNS. The data concerning the years spanning 1987 to 1989 and the emerging conclusions will be presented. Also, important and meanwhile accepted suggestions for the founding and equipment of rehabilitative care units will be discussed.

Brain Damage, Chronic↗
PubMed1977

Evoked brain potentials and disability in brain-damaged patients.

Various measures of evoked brain potential abnormality (EPA) were correlated with disability ratings (DR) for 35 brain-damaged patients. EPA data consisted of judgements of abnormality of ipsilateral, contralateral and bilateral responses to auditory and visual stimuli reflecting activity in the brain stem, subcortex and cortex. DR data were obtained from a scale developed for this study to quantize and categorize patients with a wide range of disabilities from coma to normal functioning. EPA scores based on visual and auditory cortical responses showed significantly positive correlations with degree of disability. Visual response correlation was .49, auditory .38 and combined visual and auditory .51. It was concluded that EPA measures can reflect disability independently of clinical information. They are useful in assessing brain function in general and, specifically, in assessing impairment of sensory function. The evoked potential technique was particularly useful in patients who were not able to participate fully in their own examination. There were indications that the technique may also be valuable in monitoring progress and in predicting clinical outcome in brain-damaged patients.

Adult↗
PubMed2004

Flotillin-1 in the substantia nigra of the Parkinson brain and a predominant localization in catecholaminergic nerves in the rat brain.

The substantia nigra cells of a normal and Parkinson's disease human brain were obtained by the micropunch procedure and total RNA was isolated. Differential display RT-PCR of the total RNA revealed differentially expressed cDNAs that were identified by sequencing. This resulted in the identification of a panel of known and unknown differentially expressed genes. Complex I (NADH ubiquinone oxidoreductase) and Complex IV (cytochrome oxidase) whose expressions are decreased in Parkinson's disease were reduced in the Parkinson brain. Of the various differentially expressed genes, flotillin-1, also known as reggie-2, was of great interest to us. It is a relatively new protein which is an integral membrane component of lipid rafts and has been implicated in signal transduction pathway events. In situ hybridization histochemical studies with human and rat brain sections revealed the presence of this mRNA in discrete neuronal (and possibly glial) cells of the substantia nigra, locus coeruleus, cortex, hippocampus, hypothalamus, thalamus, motor nuclei, nucleus basalis, raphe nucleus, and other brain regions. Immunohistochemical studies revealed that flotillin-1 is not present in all the regions where the message was found. In the rat brain, the most prominent observation was the revelation of all catecholamine cells (dopamine, norepinephrine, epinephrine) by the flotillin-1 antibody (1:100 dilution). At a more concentrated dilution (1:10) other neuronal cells (e.g., cortex, thalamus, hindbrain) were observed. At both dilutions dense dopaminergic fibers were observed in the rat caudate-putamen, nigrostriatal tract, and substantia nigra. It is significant that there is an increased gene expression of flotillin-1 in the Parkinson substantia nigra/ventral tegmental area. The role of flotillin in these cells is unclear although it is interesting that the reggie-2/flotillin-1 gene was upregulated during retinal axon regeneration in the goldfish visual pathway (Schulte et al., Development 124:577-87, 1997) which suggests that flotillin-1/reggie-2 might play a role in axonal growth from the remaining substantia nigra cells of the Parkinson brain.

Aged↗
PubMed2003

Regional brain cooling induced by vascular saline infusion into ischemic territory reduces brain inflammation in stroke.

The neuroprotective effect of hypothermia has long been recognized. Use of hypothermia for stroke therapy, which is currently being induced by whole body surface cooling, has been largely limited because of management problems and severe side effects (i.e., pneumonia). Our recent studies have demonstrated the significant therapeutic value of local brain cooling in the ischemic territory prior to reperfusion in stroke. The goal of this study was to determine if cerebral local cooling infusion could reduce stroke-mediated brain injury by inhibiting inflammatory responses. A hollow filament was used to block the middle cerebral artery (MCA) for 3 hours, and then to locally infuse the ischemic territory with 6 ml cold saline (20 degrees C) for 10 min prior to 48-h reperfusion. This cold saline infusion significantly ( P<0.01) reduced temperature of the MCA supplied territory (in cerebral cortex from 37.2+/-0.1 degrees C to 33.4+/-0.4 degrees C, in striatum from 37.5+/-0.2 degrees C to 33.9+/-0.4 degrees C), with the hypothermia remaining for at least 45 min after reperfusion. Consequently, significant ( P<0.01) reductions in endothelial expression of intracellular adhesion molecule-1 (ICAM-1), the key step for inflammatory progress, as well as leukocyte infiltration, were evident in both cortex and striatum after reperfusion. As a control, ischemic rats received the same amount of cold saline systemically through a femoral artery. A mild hypothermia was induced in the cerebral cortex (35.3+/-0.2 degrees C) but not in the striatum (36.8+/-0.2 degrees C). The reduced cortical temperature returned to normal within 5 min. Brain temperature in ischemic rats perfused locally with saline at 37 degrees C remained normal. Intensive expression of ICAM-1 and accumulation of leukocytes was observed in ischemic control groups without brain cooling infusion. In conclusion, brain hypothermia induced by local pre-reperfusion infusion ameliorated brain inflammation from stroke.

Analysis of Variance↗
PubMed1984

Subcellular distribution of somatostatin-14, somatostatin-28 and somatostatin-28 (1-12) in rat brain cortex and comparisons of their respective binding sites in brain and pituitary.

Subcellular distribution and binding characteristics of the three endogenous peptides somatostatin-14 (SRIF-14), somatostatin-28 (SRIF-28) and somatostatin-28(1-12) (SRIF-28(1-12] derived from preprosomatostatin were investigated in the rat brain cortex. The three peptides are predominantly recovered from a crude mitochondrial pellet (P2), containing the pinched off nerve endings. Specific high affinity binding sites for 125I-N-Tyr-SRIF-14 and 125I-N-Tyr-SRIF-28 are present on pituitary and brain membranes. Under the same conditions, 125I-N-Tyr-SRIF-28(1-12) binding is undetectable. Moreover, SRIF-28(1-12) does not displace 125I-N-Tyr-SRIF-14 or 125I-N-Tyr-SRIF-28 binding. SRIF-28 is more potent than SRIF-14 to displace 125I-N-Tyr-SRIF-28 binding to brain and pituitary membranes, while both peptides are equipotent to displace 125I-N-Tyr-SRIF-14 binding. Finally, the regional distribution of 125I-N-Tyr-SRIF-14 and 125I-N-Tyr-SRIF-28 binding sites in the brain is identical. In conclusion, the present results are consistent with a neurotransmitter and neurohormonal role for SRIF-14 and SRIF-28. The function of SRIF-28(1-12) in brain remains to be elucidated. Additionally, a differential role for SRIF-14 and SRIF-28 both in adenohypophysis and brain cannot be ascertained at the present time.

Animals↗
PubMed1996

Excitotoxic lesion of rat brain with quinolinic acid induces expression of p53 messenger RNA and protein and p53-inducible genes Bax and Gadd-45 in brain areas showing DNA fragmentation.

Several recent studies have demonstrated that expression of the tumour-suppressor gene p53 increases within the nervous system after injury. In various cell lines wild-type-p53, induced by DNA damage, has been shown to function to halt cell-cycle progression and under certain circumstances to induce programmed-cell death or apoptosis. Since wild type-p53 can act as a transcription factor to regulate the expression of p53-responsive genes it is possible that either, or both, functions of p53 are mediated by down-stream effector genes. However wild-type-p53 only weakly activates transcription and it remains to be determined whether p53-responsive genes are expressed in lesioned brain. Here we report that excitotoxic lesion of rat brain with the N-methyl-D-aspartate receptor agonist, quinolinic acid, induces expression of p53 messenger RNA and protein in brain regions showing delayed DNA fragmentation and that expression of p53 messenger RNA precedes DNA damage detected by terminal deoxynucleotidyl transferase-mediated dUTP-biotin nick end-labelling. In addition, using in situ hybridization and immunocytochemistry we demonstrate increased expression of the p53-responsive gene Gadd-45 (preceding p53 expression) and re-expression of the p53-responsive gene Bax (following p53 expression), in these same areas. Bax has been shown to promote neuronal death by interacting with Bcl-2 family members while Gadd-45 expression has been associated with suppression of the cell-cycle and DNA repair. These results suggest that p53 protein may function as an active transcription factor in lesioned brain perhaps initiating the re-expression of Bax in injured brain regions. However, since Gadd-45 precedes p53 expression it appears unlikely that p53 is involved in regulating the early expression of Gadd-45. Taken together however, these results suggest that p53, Bax and Gadd-45 may play important roles in the response (damage/recovery) of the brain following excitotoxic injury.

Animals↗
PubMed1996

A novel carbon fiber bundle microelectrode and modified brain slice chamber for recording long-term multiunit activity from brain slices.

The fabrication and characteristics of a novel multiunit recording electrode and modified brain slice chamber suitable for long-term recording from brain slices are described. The electrode consisted of an electrolyte-filled glass micropipette with a 20-50 microns thick wax-coated bundle of 5-micron diameter carbon fibers extending 2.5 cm from the tapered end and an AgCl-coated silver wire inserted into the open end and connected to a preamplifier. Both ends of the electrode were sealed with wax to prevent evaporation of the electrolyte. The brain slice was maintained over this extended period in an interface-type brain slice chamber modified to completely surround the slice with medium. Using this electrode, regular 24-h oscillations of spontaneous multiunit activity were recorded for 3 days from a single location in a 500 microns thick rat suprachiasmatic nucleus brain slice. Preliminary data suggest that this novel carbon fiber bundle electrode will be a favorable alternative to traditional metal electrodes for long-term recording of multiunit activity from brain slices.

Animals↗
PubMed1971

Mescaline-induced changes of brain-cortex ribosomes. Role of sperimidine in counteracting the destabilizing effect of mescaline of brain-cortex ribosomes.

1. The effect of spermidine on the mescaline-induced changes of brain-cortex ribosomes was studied by adding spermidine during the treatment of goat brain-cortex slices with mescaline. 2. Mescaline treatment of brain-cortex slices removed a portion of the endogenous spermidine from ribosomes and this removal was significantly prevented when spermidine was present during mescaline treatment. 3. Spermidine present during mescaline treatment of brain-cortex slices counteracted, to some extent, the destabilizing effect of mescaline on ribosomes with respect to heat denaturation. 4. Mescaline treatment of brain-cortex slices made ribosomes more susceptible to breakdown, releasing protein and RNA, and resulting in loss of ribosomal enzymic activities. However, spermidine present during mescaline treatment counteracted moderately the mescaline-induced ribosomal susceptibility to breakdown and ribosomal loss of enzymic activities. 5. Ribosomes of mescaline-treated cortex slices were rapidly degraded by ribonuclease and trypsin. However, if spermidine was present during mescaline treatment of brain-cortex slices the rates of degradation diminished.

Animals↗
PubMed2002

Regional quantitative study of formation process of neurofibrillary tangles in the hippocampus of non-demented elderly brains: comparison with late-onset Alzheimer's disease brains.

We quantitatively investigated the formation process of neurofibrillary tangles (NFT) in the hippocampus of 32 brains from non-demented elderly persons using tau-immunohistochemistry, compared with 13 brains from patients with late-onset Alzheimer's disease (AD). The 32 non-demented elderly brains were classified into 16 brains in group I and 16 brains in group II mainly based on the distribution of tau-positive neurons in the hippocampus. Tau-positive neurons were found predominantly in the CA2 in group I, while they were found predominantly in the subiculum-pre-CA1 in group II. Most late-onset AD brains showed a distribution of tau-positive neurons similar to that in group II. In addition, the distribution pattern of tau-positive neurons in the hippocampus was closely related to degeneration of the perforant pathway with the accumulation of tau. These findings suggest that NFT occur first in the CA2 and extend to the subiculum-pre-CA1 in group I, while they occur first in the subiculum-pre-CA1 and extend to the CA2 later in group II, and that the NFT occurring in the subiculum-pre-CA1 are mainly related to degeneration of the perforating route and in the CA2 are related to the degeneration of the non-perforating route.

Aged↗
PubMed2006

Brain drain of doctors from southern Africa: brain gain for Australia.

"Brain drain" is the depletion or loss of intellectual and technical personnel. The United Nations defines it as a one-way movement of highly skilled people from developing to developed countries that only benefits the industrialised (host) world. Today, brain drain is a major problem facing less developed countries, while Australia and other developed countries are the beneficiaries. Brain drain is reported to have direct negative impact on the population's health status in the donor country, with associated consequences for the productivity and welfare of the population. This paper reports on a qualitative study to understand the key factors behind brain drain from the perspective of the migrating doctor, and to consider possible solutions. Interviews were conducted with doctors who have migrated to Australia from southern Africa to explore reasons for brain drain. Specifically, the study tests the supposition that push factors play a much greater role than pull factors, and identifies which push factors are most important. Strategies to prevent brain drain from this depleted labour region are considered.

Adult↗
PubMed1996

Brain mast cell degranulation regulates blood-brain barrier.

Mast cells synthesize vasoactive agents and a number of neurotransmitters. They are particularly numerous in the medial habenular region of the epithalamus, the attachment site of the choroid plexus. The present study examined whether degranulation of brain mast cells alters the permeability of the blood-brain barrier (BBB). To this end, doves were injected intramuscularly with the mast cell degranulator, compound 48/80 (C40/80), followed by i.v. injection of Evans blue. The distribution of the dye in the parenchyma was examined using digital imaging. Three brain areas were analyzed: the medial habenula (which also contains mast cells), the paraventricular nucleus (PVN, which abuts the third ventricle, but has no mast cells), and the lateral septal organ (LSO, a circumventricular organ with fenestrated capillaries). Significantly more Evans blue tracer and fewer toluidine blue-positive mast cells were detected in the medial habenula of subjects treated with C48/80 compared to saline controls. Evans blue did not enter the PVN in either the experimental or control group, while it entered the LSO equally in both. Degranulation of mast cells after C48/80 treatment was confirmed histochemically and ultrastructurally. The results support the hypothesis that brain mast cell degranulation locally alters BBB permeability. Activation of brain mast cells may provide a mechanism for regulated opening of the BBB.

Animals↗
PubMed2000

Chemical mapping of anxiety in the brain of healthy humans: an in vivo 1H-MRS study on the effects of sex, age, and brain region.

We recently presented results in an in vivo study of human brain chemistry in 'physiologic' anxiety, i.e., the anxiety of normal everyday life. Normal subjects with high anxiety demonstrated increased concentration of chemicals in orbital frontal cortex (OFC) as compared to lower anxiety. In a separate study of aging we demonstrated a decrease of total chemical concentration in OFC of middle-aged subjects, as compared with younger age. This brain region also showed gender dependence; men demonstrating decreased chemical concentration compared to women. We hypothesized that these sex- and age-dependent differences in OFC chemistry changes are a result of anxiety effects on this brain region. In the present study we examined these sex- and age-differential regional brain chemistry changes (as identified by localized in vivo proton magnetic resonance spectroscopy [1H-MRS]) in relation to the state-trait-anxiety (as measured by the State-Trait Anxiety Inventory) in 35 healthy subjects. The concentrations for all nine chemicals of 1H-MRS spectra were measured relative to creatine across multiple brain regions, including OFC in the left hemisphere. Analysis of variance showed anxiety-specific effects on chemical concentration changes in OFC, which were different for both sexes and age groups. Male subjects showed larger effect of anxiety on OFC chemistry as compared to females when the same sex high-anxiety subjects were compared to lower anxiety. Similarly, middle-aged subjects showed larger effect of anxiety on OFC chemistry as compared to younger age when the same age subjects with high anxiety were compared to lower anxiety. Largest effect of anxiety on OFC chemistry was due to changes of N-Acetyl aspartate. The results indicate that the state-trait anxiety has sex- and age-differential patterns on OFC chemistry in healthy humans, providing new information about the neurobiological roots of anxiety.

Adult↗
PubMed1988

The glucose transporter of the human brain and blood-brain barrier.

We identified and characterized the glucose transporter in the human cerebral cortex, cerebral microvessels, and choroid plexus by specific D-glucose-displaceable [3H]cytochalasin B binding. The binding was saturable, with a dissociation constant less than 1 microM. Maximal binding capacity was approximately 7 pmol/mg protein in the cerebral cortex, approximately 42 pmol/mg protein in brain microvessels, and approximately 27 pmol/mg protein in the choroid plexus. Several hexoses displaced specific [3H]cytochalasin B binding to microvessels in a rank-order that correlated well with their known ability to cross the blood-brain barrier; the only exception was 2-deoxy-D-glucose, which had much higher affinity for the glucose transporter than the natural substrate, D-glucose. Irreversible photoaffinity labeling of the glucose transporter of microvessels with [3H]cytochalasin B, followed by solubilization and polyacrylamide gel electrophoresis, labeled a protein band with an average molecular weight of approximately 55,000. Monoclonal and polyclonal antibodies specific to the human erythrocyte glucose transporter immunocytochemically stained brain blood vessels and the few trapped erythrocytes in situ, with minimal staining of the neuropil. In the choroid plexus, blood vessels did not stain, but the epithelium reacted positively. We conclude that human brain microvessels are richly endowed with a glucose transport moiety similar in molecular weight and antigenic characteristics to that of human erythrocytes and brain microvessels of other mammalian species.

Adult↗
PubMed2003

Metallothionein-I overexpression alters brain inflammation and stimulates brain repair in transgenic mice with astrocyte-targeted interleukin-6 expression.

Transgenic expression of IL-6 in the CNS under the control of the GFAP gene promoter, glial fibrillary acidic protein-interleukin-6 (GFAP-IL-6) mice, raises an inflammatory response and causes significant brain damage. However, the results obtained in the GFAP-IL-6 mice after a traumatic brain injury, such as a cryolesion, demonstrate a neuroprotective role of IL-6. Thus, the GFAP-IL-6 mice showed faster tissue repair and decreased oxidative stress and apoptosis compared with control litter-mate mice. The neuroprotective factors metallothionein-I+II (MT-I+II) were upregulated by the cryolesion to a higher extent in the GFAP-IL-6 mice, suggesting that they could be related to the neuroprotection afforded by the transgenic expression of IL-6. To examine this possibility, we have crossed GFAP-IL-6 mice with transgenic mice overexpressing MT-I (TgMT), producing double transgenic GFAP-IL-6 TgMT mice. The results obtained after cryolesion in GFAP-IL-6 TgMT mice, as well as in TgMT mice, consistently supported the idea that the increased MT-I+II levels observed in GFAP-IL-6 mice are a fundamental and important mechanism for coping with brain damage. Accordingly, MT-I overexpression regulated the inflammatory response, decreased oxidative stress and apoptosis significantly, and increased brain tissue repair in comparison with either GFAP-IL-6 or control litter-mate mice. Overall, the results demonstrate that brain MT-I+II proteins are fundamental neuroprotective factors.

Animals↗
PubMed2005

Dominant expression of androgen receptors and their functional regulation of organic anion transporter 3 in rat brain capillary endothelial cells; comparison of gene expression between the blood-brain and -retinal barriers.

Brain and retinal capillary endothelial cells (BCECs and RCECs, respectively) exhibit a barrier structure and function. Comparison of gene expression in these cells could clarify the selective function of each barrier. The purpose of this study was to identify the genes selectively expressed at the blood-brain barrier (BBB) and to clarify the function of the selective gene, androgen receptor (AR). Gene expression was compared by a differential display using conditionally immortalized rat BCECs and RCECs (TR-BBB and TR-iBRB, respectively). A total of 12 gene fragments were identified as the selective genes dominantly expressed in TR-BBB cells. The most selective fragment in TR-BBB cells had the highest homology with the 3'-UTR of human and mouse AR. Rat AR mRNA was detected in TR-BBB cells and the brain capillary rich fraction, but not in TR-iBRB cells. Expression of organic anion transporter 3 (OAT3) mRNA in TR-BBB cells was induced by treatment with dihydrotestosterone (DHT), an AR ligand, and this induction was suppressed by flutamide. Moreover, uptake of benzylpenicillin by TR-BBB cells was also induced by DHT treatment. In contrast, OAT3 mRNA expression in TR-iBRB cells was not affected by DHT treatment. The brain-to-blood efflux rate of benzylpenicillin was not affected by gender. These results suggest that AR is involved in the functional regulation of OAT3 at the BBB, but not at the inner blood-retinal barrier (iBRB), and this regulation is not affected by gender. The BBB function will be affected by the androgen levels in the brain and/or plasma via AR.

Animals↗
PubMedDate not supplied

In vivo validation of tissue segmentation based on a 3D feature map using both a hamster brain tumor model and stereotactically guided biopsy of brain tumors in man.

The purpose of this study was to validate our MR tissue segmentation technique using a hamster brain tumor model and malignant brain tumors in man. We used a multispectral tissue segmentation analysis. Three sets of MRI data were included: proton density, T2-weighted fast spin echo, and T1-weighted spin echo, as inputs. Three image preprocessing steps included correcting image nonuniformity, application of an anisotropic diffusion type filter, and data point selection by a qualified observer. We used the k-Nearest Neighbor segmentation algorithm, which does not require prior knowledge of the sample distribution. This choice allowed us to optimize the different tissue clusters present in three-dimensional (3D) feature space. In vivo validation of the technique was performed in hamsters harboring tumors induced with JC virus-transformed HJC-15 cells, as compared to three control animals. Human brain tumors obtained by stereotactically guided biopsy in six patients were also included in the study. Finally, brain tumors were removed from two patients who underwent conventional craniotomy using segmentation-derived images as a guide. In the hamsters, 10 tissues were correctly identified by segmentation and were confirmed histologically (P < .02). In the patients, there was also a strong correlation between our segmentation results and the tissue obtained by stereotactic biopsy (P < .01). In one of the two patients who underwent open craniotomy, segmentation images were useful in revealing tumor spread into vital areas of the brain (motor area). In conclusion, the results of segmentation correlate well with the tissues in vivo and thus warrant further clinical utilization and evaluation.

Adult↗