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Results for “brain microenvironment”

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PubMed1998

NMR studies of intra- and extracellular red blood cell lithium by transverse relaxation measurements and shift reagents.

Lithium salts are used in the treatment and prophylaxis of bipolar or mood disorders. The mechanism of action by which the cation exerts its therapeutic influence is unknown. A knowledge of brain Li concentration, its distribution in the brain, and its properties in the cellular microenvironment may have a strong influence on the understanding of Li function. The differentiation of lithium in the intra and extracellular environments has been achieved in a noninvasive manner in red blood cell (RBC) model. The two distinct transverse relaxation (T2) components have been observed in the blood sample drawn from lithium treated rats. These results indicate two different environments for Li with a fast (T2f) and a slow (T2s) component in the RBC model corresponding fractions that contribute to each relaxation component. The results compare well with the intra- and extracellular RBC lithium measured using shift reagents. Our studies indicate that the T2 method has utility in estimating the intracellular Li in systems that exhibit similar T2 behavior. The studies performed at different Li doses in the rat model indicate that the method may have utility in following a wide range of intracellular Li.

Animals↗
PubMedDate not supplied

[Ethanol sensitivity of rat brain cortex Na(+), K(+)-ATPase in plasma membrane structural damage induced by sodium dodecyl sulfate].

To investigate the role of rat brain cortex Na+, K(+)-ATPase plasma membrane microenvironment in ethanol effect in vitro on membrane the sensitivity of enzyme activity to alcohol was studied under membrane perturbation induced by sodium dodecyl sulfate. The increase of enzyme sensitivity to detergent inactivation in the presence of high ethanol concentrations and to alcohol inhibition after modification by Ds-Na was revealed. It is supposed that Na+, K(+)-ATPase sensitivity to ethanol is dependent on structural state of protein microenvironment in accordance with assumed differences in structural organization of the boundary lipids of the neuronal enzyme isoforms.

Animals↗
PubMed1993

The blood-brain barrier: cellular basis.

Perfusion experiments with horseradish peroxidase have established that the morphological substrate of the blood-brain barrier is represented by microvascular endothelial cells. They are characterized by complexly arranged tight junctions and a very low rate of transcytotic vesicular transport. They express transport enzymes, carrier systems and brain endothelial cell-specific molecules of unknown function not expressed by any other endothelial cell population. These blood-brain barrier properties are not intrinsic to these cells but are inducible by the surrounding brain tissue. Type I astrocytes injected into the anterior eye chamber of the rat or onto the chick chorioallantoic membrane are able to induce a host-derived angiogenesis and some blood-brain barrier properties in endothelial cells of non-neural origin. Recently we have shown that this cellular interaction is due to the secretion of a soluble astrocyte derived factor(s). Astrocytes are also implicated in the maintenance, functional regulation and the repair of the blood-brain barrier. Complex interactions between other constituents of the microenvironment surrounding the endothelial cells, such as the basement membrane, pericytes, nerve endings, microglial cells and the extracellular fluid, take place and are required for the proper functioning of the blood-brain barrier, which in addition is regionally different as reflected by endothelial cell heterogeneity.

Animals↗
PubMed1988

A possible role for taurine in osmoregulation within the brain.

Intracranial microdialysis was used to measure changes in extracellular amino acids within the rat brain during local osmotic alteration of the extracellular microenvironment or during systemic water intoxication. Increased cellular hydration produced by either of these methods was accompanied by a marked increase in extracellular taurine levels without affecting the other amino acids measured. With local osmotic alteration, this increase was osmolarity dependent and reversible. The specificity, sensitivity, and reversibility of the increase in extracellular taurine strongly suggest a functional role in osmoregulation in the brain under normal as well as pathological conditions.

Animals↗
PubMed1995

Fluorine-19 nuclear magnetic resonance imaging and spectroscopy of sevoflurane uptake, distribution, and elimination in rat brain.

BACKGROUND: Determination of macroscopic and microscopic distribution of general anesthetics can facilitate identification of anatomic, cellular, and molecular loci of anesthetic action. Previous attempts to measure brain anesthetic distributions with fluorine-19 (19F) nuclear magnetic resonance (NMR) imaging were conducted at magnetic field strengths lower than 2 Tesla. All have produced only silhouettes of brain tissue. Difficulties intrinsic to NMR imaging of anesthetics include higher anesthetic solubility in extracranial tissues and the lower limits to spin-echo delay times that can be used in conventional NMR imaging methods. So far, such methods have been unable to capture rapidly decaying brain 19F NMR signals. METHODS: 19F NMR imaging and spectroscopy were conducted at 4.7 Tesla using a specially developed NMR probe and new imaging methods. With the new techniques, it was possible to observe directly the uptake, distribution, and elimination in brain of sevoflurane, a fluorinated general anesthetic with special advantages for NMR investigations. RESULTS: 19F NMR images, acquired at different times after sevoflurane administration, clearly showed the distribution of a fluorinated general anesthetic within the brain. Based on continuous transverse relaxation time measurements, sevoflurane signals could be separated into two components, attributable respectively to sevoflurane in a mobile or immobile microenvironment. During washin, there was a delayed accumulation of anesthetic in the mobile microenvironment. During washout, there was a rapid elimination from the immobile microenvironment. CONCLUSIONS: At anesthetizing concentrations, sevoflurane distributes heterogeneously in the brain. Sevoflurane in the brain tissue contributes mostly to the immobile component of the 19F signal, whereas that in the surrounding adipose and muscle tissues contributes mostly to the mobile component. Imaging and spectroscopic results suggest that the immobile component of sevoflurane is associated with the general anesthetic effects of the agent.

Anesthetics↗
PubMedDate not supplied

Differential expression of connexin43 in foetal, adult and tumour-associated human brain endothelial cells.

Connexin43 (Cx43), the main protein constituting the gap junctions between astrocytes, has previously been demonstrated in endothelial cells of somatic vessels where the intercellular coupling that it provides plays a role in endothelial proliferation and migration. In this study, Cx43 expression was analysed in human brain microvascular endothelial cells of the cortical plate of 18-week foetal telencephalon, in adult cerebral cortex and glioma (astrocytomas). The study was carried out by immunocytochemistry utilizing a Cx43 monoclonal antibody and a polyclonal antibody anti-GLUT1 (glucose transporter isoform 1) to identify the endothelial cells and to localize Cx43. Endothelial Cx43 is differently expressed in the cortical plate, cerebral cortex and astrocytoma. Within the cortical plate and tumour, Cx43 is highly expressed in microvascular endothelial cells whereas it is virtually absent in the cerebral cortex microvessels. The high expression of the gap junction protein in developing brain, as well as in brain tumours, may be related to the growth status of the microvessels during brain and tumour angiogenesis. The lack of endothelial Cx43 in the cerebral cortex is in agreement with the characteristics of the mature brain endothelial cells that are sealed by tight junctions. In conclusion, the results indicate that endothelial Cx43 expression is developmentally regulated in the normal human brain and suggest that it is controlled by the microenvironment in both normal and tumour-related conditions.

Adult↗
PubMed2005

Resting microglial cells are highly dynamic surveillants of brain parenchyma in vivo.

Microglial cells represent the immune system of the mammalian brain and therefore are critically involved in various injuries and diseases. Little is known about their role in the healthy brain and their immediate reaction to brain damage. By using in vivo two-photon imaging in neocortex, we found that microglial cells are highly active in their presumed resting state, continually surveying their microenvironment with extremely motile processes and protrusions. Furthermore, blood-brain barrier disruption provoked immediate and focal activation of microglia, switching their behavior from patroling to shielding of the injured site. Microglia thus are busy and vigilant housekeepers in the adult brain.

Animals↗
PubMed1995

Experimental therapies to improve delivery of oxygen and substrate in acute stroke.

The results of large-scale clinical trials of hemodilution therapy and vasodilators for acute stroke have been disappointing. However, interventions involving the manipulation of whole blood viscosity, blood oxygen-carrying capacity, cardiac output, and the resistance properties of cerebral vessels are viable therapeutic modalities currently being investigated. The central aim of all of these therapies is the timely improvement of perfusion and substrate delivery to ischemic brain regions. Better understanding of cerebrovascular flow regulation and the physiology of microvessels may give rise to more effective therapies. In the past, overemphasis on hematocrit reduction and cerebral vasodilators has obscured the potential risks of reducing blood oxygen content and vascular resistance during acute stroke and the importance of optimizing oxygen delivery by other means, in particular by cardiac output augmentation and manipulation of plasma properties. A broader approach to therapeutic strategies for acute stroke includes not only increasing cerebral blood flow, but also interventions that will create favorable changes in the humoral microenvironment and promote overall substrate delivery to the brain.

Acute Disease↗
PubMed2006

Novel cell therapy approaches for brain repair.

Numerous reports elucidate that tissue-specific stem cells are phenotypically plastic and their differentiation pathways are not strictly delineated. Although the identity of all the epigenetic factors which may trigger stem cells to make a lineage selection are still unknown, the plasticity of adult stem cells opens new approaches for their application in the treatment of various disorders. There is increasing researcher interest in hematopoietic stem cells for treatment of not only blood-related diseases but also various unrelated disorders including neurodegenerative diseases. Human umbilical cord blood (hUCB) cells, due to their primitive nature and ability to develop into nonhematopoietic cells of various tissue lineages, including neural cells, may be useful as an alternative cell source for cell-based therapies requiring either the replacement of individual cell types and/or substitution of missing substances. Here we focus on recent findings showing the robustness of adult stem cells derived from hUCB and their potential as a source of transplant cells for the treatment of diseased or injured brains and spinal cords. Depending upon the pathological microenvironment in which the hUCB cells are introduced, neuroprotective and/or trophic effects of these cells, from release of various growth or anti-inflammatory factors to moderation of immune-inflammatory effectors, may be more likely than neural replacement. These protective effects may prove essential to maintaining restored tissue integrity over the course of various diseases or injuries.

Amyotrophic Lateral Sclerosis↗
PubMed1995

Effect of long-term treatment with the dihydropyridine-type calcium channel blocker darodipine (PY 108-068) on the cerebral capillary network in aged rats.

The effects of treatment with the dihydropyridine Ca+2 antagonist darodipine (PY 108-068) on age-related changes in the cerebral capillary network was studied using alkaline phosphatase histochemistry with quantitative image analysis. The investigation was performed on male Wistar rats of 12 months (adult reference group) and 27 months. The 27-month-old rats consisted of two groups, the first of control untreated animals and the second of rats receiving an oral dose of 5 mg/kg/day of darodipine from the 21st to the 27th month. The cerebral areas examined included the frontal cortex, the occipital cortex, Ammon's horn of the hippocampus, and the dentate gyrus. The number and the average length of alkaline phosphatase-positive capillaries were decreased in old rats, when compared with adult rats. The intercapillary distance, which is considered as a sensitive parameter for capillary density was increased in aged rats in comparison to adult rats. The capillary diameter was increased slightly or unchanged in old rats. The Ammon's horn and the frontal cortex were the cerebral areas most affected by age-dependent changes of the capillary network. Treatment with darodipine increased the number and the average length of alkaline phosphatase-reactive capillaries and reduced the intercapillary distance and the diameter of cerebral capillaries in old rats. The pericapillary microenvironment of the Ammon's horn was the most sensitive to treatment with darodipine. The above results showed that treatment with darodipine is capable of counteracting some microvascular changes occurring in the brain of aged rats. This suggests that the blockade of dihydropyridine-type Ca2+ channels has a positive effect on the brain microvascular system and may counteract the impairment of pericapillary microenvironment occurring with aging.

Aging↗
PubMed1975

Neuronal--glial interactions during development and aging.

Integration of the central nervous system is an expression of cerebral homeostasis that is essential for the internal ability of the organism to adapt to its changing environment throughout life. It is generally accepted that neurons undergo no further division after differentiation, whereas glial cells continue to proliferate throughout life. The increase in glial cells with advanced age may reflect a compensatory process of the brain to overcome neuronal loss or neuronal functional changes that may occur with age. Therefore, these neuronal-glial interactions during development and aging may play a key role in the integrative capacity of the brain. One of the mechanisms contributing to brain stability is the blood-brain barrier, which regulates the neuronal-glial microenvironment in the mature organism. Neuronal intercommunication is mediated via neurotransmitter substances and a shift may occur from excitation to inhibition and vice versa in some CNS areas with aging. Studies of some aspects of cholinergic, monoaminergic and amino acid neurotransmission show that their maturational patterns are CNS-area specific and that some neurotransmitter processes decline with advanced age. Glial cells, besides participating in the regulation of extraneuronal environment, are also proposed to be involved in neurotransmission mechanisms in the adult and aging CNS and since they are the major CNS cellular compartment that changes with age they may thus contribute significantly to the maintenance of CNS integrative ability and adaptation with age.

Acetylcholinesterase↗
PubMed1987

The dendrites of single brain-stem motoneurons intracellularly labelled with horseradish peroxidase in the cat. An ultrastructural analysis of the synaptic covering and the microenvironment.

Two laryngeal motoneurons intracellularly stained with horseradish peroxidase were studied ultrastructurally. The precise position of the ultrastructural observations made along the dendrites was obtained from the computer-reconstruction of the motoneurons in three dimensions. The shape and the size of the synaptic boutons, the percentage of membrane covered by bouton appositions and active zones, the number of boutons per 100 microns2 (packing density) were analysed on the soma and on the labelled dendrites at different distances from the soma up to 1000 microns. The results revealed no important regional differences in the mean length of synaptic apposition. The packing density was in the range of 9.3-14.9 boutons per 100 microns2 and was not correlated with the distance from the soma. The percentage apposition covering was higher on the soma and the proximal part of the dendrites than on the remaining part of the dendritic arborization. Close appositions between labelled dendrite and unlabelled somata and/or dendrites together with dendro-dendritic synapses suggested the possibility that the dendrites may be involved in local cell-to-cell communication. Microdendrites emerging from the soma or the proximal dendrites were contacted by synaptic boutons which may be more efficient as revealed by computation.

Animals↗
PubMed2001

A new model for diffuse brain injury by rotational acceleration: II. Effects on extracellular glutamate, intracranial pressure, and neuronal apoptosis.

The aim of this study is to monitor excitatory amino acids (EAAs) in the extracellular fluids of the brain and to characterize regional neuronal damage in a new experimental model for brain injury, in which rabbits were exposed to 180-260 krad/s2 rotational head acceleration. This loading causes extensive subarachnoid hemorrhage, focal tissue bleeding, reactive astrocytosis, and axonal damage. Animals were monitored for intracranial pressure (ICP) and for amino acids in the extracellular fluids. Immunohistochemistry was used to study expression of the gene c-Jun and apoptosis with the terminal deoxynucleotidyl transferase nick-end labeling (TUNEL) technique. Extracellular glutamate, glycine, and taurine increased significantly in the hippocampus within a few hours and remained high after 24 h. Neuronal nuclei in the granule layers of the hippocampus and cerebellum were positive for c-Jun after 24 h. Little immunoreactivity was detected in the cerebral cortex. c-Jun-positive neuronal perikarya and processes were found in granule and pyramidal CA4 layers of the hippocampus and among the Purkinje cells of the cerebellum. Also some microglial cells stained positively for c-Jun. TUNEL reactivity was most intense at 10 days after trauma and was extensive in neurons of the cerebral cortex, hippocampus, and cerebellum. The initial response of the brain after rotational head injury involves brain edema after 24 h and an excitotoxic neuronal microenvironment in the first hour, which leads to extensive delayed neuronal cell death by apoptosis necrosis in the cerebral cortex, hippocampus and cerebellum.

Acceleration↗
PubMed2005

The role of the humoral immune system in multiple sclerosis (MS) and its animal model experimental autoimmune encephalomyelitis (EAE).

The pathogenic events in multiple sclerosis (MS) that result in immune cell infiltration, multifocal demyelination and axonal loss have been focused by the strong impact of the classical MS model experimental autoimmune encephalomyelitis (EAE) towards the hypothesis that MS is an entirely T cell-mediated disease. Although conspicuous humoral immune responses have been known since Kabal's seminal finding of elevated immunoglobulins (Igs) in the cerebrospinal fluid (CSF), only in the past few years evidence derived from recent studies of the MS lesion of anti-myelin antibodies (Abs) in patients with early MS and of MS animal models has led to a renewed interest in the role for B cells, plasma cells and their products in the pathogenesis of MS. This review surveys the actual data concerning the role of the humoral immune system in MS and EAE and explains potential modes of action and long-time persistence in the inflamed brain tissue as a B cell-supportive microenvironment in MS. These mechanisms include the modulation of antigen presentation and costimulation to T cells, increased myelin opsonisation und recruitment of inflammatory cells to the CNS, but also immunoregulatory influences on the remyelination by anti-myelin B cells and Abs. So, affecting the humoral immune system in MS would be a reasonable therapeutic option.

Animals↗
PubMed2006

The transport of manganese across the blood-brain barrier.

The mammalian central nervous system (CNS) possesses a unique and specialized capillary adaptation, referred to as the blood-brain barrier (BBB). The BBB maintains an optimal neuronal microenvironment, regulating blood-tissue exchange of macromolecules and nutrients. The BBB is characterized by individual endothelial cells that are continuously linked by tight junctions, inhibiting the diffusion of macromolecules and solutes between adjacent endothelial cells. This review will focus on pertinent issues to BBB maintenance, and survey recent dogmas on the transport mechanisms for the essential metal, manganese, across this barrier. Specifically, putative carriers for manganese into and out of the brain will be discussed.

Animals↗
PubMed2000

The role of B cells and autoantibodies in multiple sclerosis.

A variety of cellular and humoral immunological abnormalities have been observed in multiple sclerosis (MS). In the past few years, several lines of evidence converged to imply an important role of autoreactive antibodies and B cells in the pathogenesis of MS. Recent data suggest that autoantibodies may be harmful in lesion formation but also potentially beneficial in repair. This review surveys recent advances in the concepts of generation and nature of pathogenetic autoantibodies, their potential modes of action, mechanisms of their long-term persistence, and the role of the inflamed brain tissue as a B-cell-supporting microenvironment in MS. Based on the presence of specific autoantibodies, it seems possible to define distinct MS subgroups in the near future. The therapeutic relevance of these new findings is presented.

Animals↗
PubMedDate not supplied

[Behavior and differentiation of the neural stem cells in vivo].

We studied the behavior and differentiation of human and rat neural stem cells after transplantation in the adult rat brain without immunosuppression. The rat stem cells were isolated from the presumptive neocortex of 15-day-old embryos. The human cells were isolated from the ventricular brain zone of 9-week-old embryos and cultivated for two weeks before transplantation. The results of histomorphological studies suggest that the microenvironment factors did not suppress the growth or development of transplanted stem cells. Both rat and human embryonic multipotent neural cells showed similar behavior and differentiation into neurons and glial cells. After transplantation, they continued to mitotically divide and migrated from the graft area to the surrounding tissue of a recipient brain. The presumptive glial cells migrated preferentially along the capillaries and fibrous structures of the recipient brain. Similar behavior of the rat and human neural stem cells in the microenvironment of the recipient adult rat brain and the absence of immune reaction suggest that the transplantation into the rat brain may serve as a model for studying the developmental biology of the human stem cells.

Animals↗
PubMed2004

Postmortem MR imaging of formalin-fixed human brain.

High-resolution postmortem neuroimaging of the brain can play a role in research programs by providing archival and reslicable images of brain specimens before permanent sectioning. These images can supplement evidence attained from both traditional neuropathological observations and in vivo neuroimaging. Differential brain tissue conspicuity, detectable with MRI, is determined by the density and mobility of water protons. Water content is about 70% in white matter, 80% in gray matter, and 99% in cerebrospinal fluid (CSF). To the extent that brain tissue contrast is determined by the number and microenvironment of water protons, timing parameters of MR image acquisition can interrogate this environment. Because the chemical environment of protons is different in living from dead tissue, optimal temporal imaging parameters, for example, for spin-echo imaging, commonly used for in vivo clinical and research study are different from those best for postmortem imaging. Here, we present a series of observations to identify relaxation times and optimal parameters for high-resolution structural imaging of formalin-fixed postmortem brain tissue using commercially available clinical scanners and protocols. Examples of high-resolution images and results from attempts at diffusion imaging are presented.

Aged↗