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At least 469 records · Page 26Linked to original sources
PubMed2002

Behavior of human neural progenitor cells transplanted to rat brain.

Human neural stem/progenitor cells provide a useful tool for studies of neural development and differentiation, as well as a potential means for neuroreplacement therapeutic needs in the human CNS. Stem cells isolated from developing human central nervous system of 8-12-week fetuses were transplanted to the forebrain and cerebellum of young and adult rats after 14 days of in vitro expansion. Cells were labeled by bisbenzimide prior to transplantation without immunosuppression. Recipient brains were examined 10 and 20 days after transplantation. Labeled stem cells were found in the neocortex, lateral ventricle and caudate nucleus in the forebrain, and in the molecular layer, Purkinje cell layer, and granular layer of the cerebellum. Mitotically dividing stem cells were observed in graft core, confirming their proliferative potential in new microenvironment. Engrafted cells migrate through the parenchyme of striatum, along the ventricular ependymal layer and callosal fibers, some of them reaching the opposite hemisphere. Some cells migrating along the capillaries express glial acid fibrillary protein, demonstrating their differentiation into astrocytes. Grafted cells expressing calbindin were found in the Purkinje cell layer, suggesting their differentiation into the Purkinje cells. At the same time, some grafted cells were undifferentiated and expressed vimentin. Our results demonstrate that cultured human neural stem/progenitor cells migrate and differentiate into both neurons and astrocytes after transplantation to the rat forebrain or cerebellum of young and adult rats.

Animals↗
PubMed2001

Vascular endothelial growth factor isoforms display distinct activities in promoting tumor angiogenesis at different anatomic sites.

The gene for the major angiogenic factor, vascular endothelial growth factor (VEGF), encodes several spliced isoforms. We reported previously that overexpression of two VEGF isoforms, VEGF(121) and VEGF(165), by human glioma U87 MG cells induced tumor-associated intracerebral hemorrhage, whereas expression of a third form, VEGF(189), did not cause vessel rupture. Here, we test whether these VEGF isoforms have distinct activities for enhancing vascularization and growth of gliomas in mice. U87 MG cells that overexpressed VEGF(165) or VEGF(189) grew more rapidly than the parental cells in both s.c. and intracranial (i.c.) locations. However, cells that overexpressed VEGF(121) only showed enhancement of i.c. tumor growth but had a minimal effect on s.c. glioma progression. At both anatomical sties, VEGF(165) and VEGF(189) strongly augmented neovascularization, whereas VEGF(121) only increased vessel density in brain tumors. In each type of glioma, expression of VEGF receptors -1 and -2 largely phenocopied the tumor vasculature, because increased VEGF/VEGF receptor-activated microvessel densities were strongly correlated with the angiogenicity and tumorigenicity elicited by the VEGF isoforms at both anatomical sites. One notable difference between the sites was the expression of vitronectin, a prototypic ligand of alpha(v)beta(3) and alpha(v)beta(5) integrins, detected in i.c. but not in s.c., gliomas. Endothelial cell migration stimulated by VEGF(121) was potentiated by vitronectin to a greater extent than that stimulated by VEGF(165). This data demonstrates that VEGF isoforms have distinct activities at different anatomical sites and suggest that the microenvironment of different tissues affects the function of VEGF isoforms.

Animals↗
PubMed2003

Neurotrophic factors attenuate microvascular permeability disturbances and axonal injury following trauma to the rat spinal cord.

Alterations of the blood-spinal cord barrier (BSCB) following spinal cord injury (SCI) and leakage of serum proteins induce vasogenic edema and cell damage. The possibility that two members of the neurotrophin family, BDNF or IGF-1 induce neuroprotection by attenuating the BSCB permeability following trauma was examined in a rat model. Repeated topical application of BDNF or IGF-1 (0.1 1microg, 0.5 microg or 1 microg in 10 microl) onto the spinal cord 30 min before SCI or 2, 5, 10 or 30 min thereafter significantly attenuated BSCB permeability to Evans blue and iodine. In the neurotrophin treated rats. edema formation, degradation of MBP, and myelin vesiculation were much less frequent compared to the untreated traumatised rats. The protective effect of BDNF and IGF-1 was most pronounced at the high dose (1 microg in 10 microl) given either 30 min before or within 10 min after SCI. The observations suggest that early intervention with neurotrophins in high doses following trauma (within 10 min) attenuates disturbances of the fluid microenvironment of the spinal cord. This indicates that BSCB opening plays an important role in SCI induced myelin vesiculation and cord pathology.

Animals↗
PubMed1993

Immune privilege as the result of local tissue barriers and immunosuppressive microenvironments.

As the cellular and molecular bases of immune privilege are elucidated experimentally, the phenomenon emerges as an active and dynamic exercise in immune regulation. Local tissue factors play a key role in the establishment and maintenance of privilege, particularly tissue cytokines and mediators within the local microenvironment, which modify both the induction and expression of immunity to antigens that are introduced into, or arise within, privileged sites.

Animals↗
PubMed2004

C6 glioma cells retrovirally engineered to express IL-18 and Fas exert FasL-dependent cytotoxicity against glioma formation.

The decreased antitumor immune response significantly contributes to the progression of glioma. To evaluate whether the antitumor immunity is restored by stable co-expression of IL-18 and Fas receptor, we retrovirally introduced these two genes into rat C6 glioma cells. We found that IL-18-transduced glioma cells secreted IL-18 and induced PBMC IFN-gamma production in vitro. We also found that Fas-transduced glioma cells were susceptible to Fas-mediated apoptosis. In vivo, we found that IL-18 expression and Fas expression synergistically inhibited C6 cell tumorigenesis with the glioma cells being subcutaneously injected in rat flank. Furthermore, we found that co-expression of IL-18 and Fas also produced a marked survival advantage with the rats being intracerebrally implanted with the glioma cells. Finally, we demonstrated that FasL-dependent PBMC cytotoxicity participated in the anti-glioma immunity induced by IL-18 and Fas expression. Taken together, these findings demonstrate that increasing IL-18 production in tumor microenvironment and prompting functional Fas receptor expression of tumor cells could enhance FasL-dependent cytotoxic antitumor immunity.

Animals↗
PubMed2005

Do tissue levels of autoantigenic aminoacyl-tRNA synthetase predict clinical disease?

The etiologies of most autoimmune diseases are not completely understood. Aminoacyl-tRNA synthetases (AARS) are a family of heterogenous enzymes responsible for protein synthesis and whose secondary functions include a role in autoimmune myositis. A subset of patients with idiopathic inflammatory myopathies demonstrate autoantibody against specific cytoplasmic AARS and the human asparaginyl-tRNA synthetase (AsnRS) has been shown to be a potent chemokine that interacts with CCR3 chemokine receptors. One way in which a chemotactic cytoplasmic enzyme might contribute to tissue inflammation is if it were abundant in a specific injured tissue and thereby released to the microenvironment at times of cellular damage. To test this hypothesis, the relative levels of AsnRS mRNA were studied in six human tissues. A 1.6 kbF RNA probe identified highly variable levels of the corresponding mRNA in Northern blot analysis of human lung, brain, heart, skeletal muscle, pancreas and liver. The highest levels of signal were noted in muscle and pancreas. Polyclonal antibody raised against recombinant human AsnRS identified abundant antigenic material in the pancreas, in particular in islet cells. Thus, the local abundance of an endogenous pro-inflammatory autoantigen may provide one explanation for perpetuation or exacerbation of tissue specific immune-mediated pathologies.

Amino Acyl-tRNA Synthetases↗
PubMedDate not supplied

Selective effect of ethanol on norepinephrine- and nicotine-induced emesis in cats.

The effect of acute ethanol administration into the cerebral ventricles of the unanesthetized cat upon emesis produced by norepinephrine and nicotine injected similarly was investigated. Ethanol inhibited the norepinephrine- and nicotine-induced emesis. The inhibitory effect of ethanol occurred after a transient and inconsistent emetic action of the drug. Ethanol was about 10 times more potent inhibiting the emesis caused by nicotine. On the other hand, intracerebroventricular ethanol had virtually no effect on emesis produced by intragastric copper sulfate. The inhibitory effect of ethanol is ascribed to an action on alpha-noradrenergic and nicotinic receptors in the area postrema. Differential responses to ethanol most probably reflect the microenvironment of alpha-noradrenergic and nicotinic synapses in the area postrema of the cat.

Animals↗
PubMed1980

Phenotypic expression of I-A and I-E/C subregion determinants on murine thymocytes.

The expression of Ia antigens on murine thymocytes has been assessed by indirect immunofluorescence and flow microfluorometry analysis. Antisera specific for I-region determinants were found to react with at least 50% of thymus cells in single-cell suspensions. When these antisera were tested on thymus cells of an appropriate recombinant strain, it was found that both I-A and I-E/C subregion determinants could be detected. Monoclonal antibodies to I-A and to I-E determinants also reacted with thymus cells in a similar fashion, eliminating the possibility that contaminating specificities accounted for the reactivity of alloantisera. The majority of Ia-positive thymus cells appeared to express determinants encoded by genes of both I-A and I-E/C subregions. Ia expression on individual thymocytes was also correlated with cell size as measured by forward light scatter intensity. However, unlike antigens detected by rabbit anti-mouse brain antisera, Ia antigens did not appear to be associated with known subpopulations of thymocytes distinguishable by light scatter intensity. The presence of I-region encoded antigens on thymocytes may play a role in maturation of T cells in the thymus microenvironment.

Animals↗
PubMed1994

[Correlation of organ pathology and distribution of virus replicating cells, demonstrated with RNA in situ hybridization of SIVmac infection of Macaca mulatta].

22 juvenile rhesus macaques were infected i.v. with SIVmac and killed at defined timepoints after infection. Productively infected cells were detected by RNA in situ hybridization in the paraffin material. Their number was correlated with the pathology of lymph nodes, thymus, extranodal lymphatic parenchyma and other organs. In the first weeks all lymphatic tissues and compartments got infected, as well as the brain, the bone marrow and other organs. The high virus replication during this first phase disappeared with the onset of the seroconversion and remained low during all stages of atrophy of the lymphatic parenchyma. The atrophy of the lymphatic parenchyma and its microenvironment was not correlated with virus replication. This may implicate that a virostatic therapy might be more successful in the first weeks of infection.

Animals↗
PubMed2004

CXCL12 in malignant glial tumors: a possible role in angiogenesis and cross-talk between endothelial and tumoral cells.

CXCL12 (stromal cell-derived factor-1/CXCL12) regulates leukocyte, endothelial and hematopoietic precursor migration, bone-marrow myelopoiesis and angiogenesis. CXCL12 and its receptor CXCR4 are over-expressed in malignant gliomas, which are highly vascularized tumors with a poor prognosis. We studied the expression of CXCL12 and CXCR4 in glioma cell lines, endothelial cells, tissue sections and endocavitary fluids from patients with gliomas. We then analyzed the proliferative and the apoptotic effect of CXCL12 in endothelial cells and glioma primary cultures. We observed the release of CXCL12 in supernatants of human brain microvascular endothelial cells and at variable levels, in post-surgical endocavitary fluids. CXCL12 was expressed in both glioma and endothelial cells as assessed by immunostaining of surgical brain sections. CXCR4 was found in cells lines and primary cultures from malignant gliomas as well as in endothelial cells and was increased by vascular endothelial growth factor and basic fibroblast growth factor (bFGF). CXCL12 inhibited bFGF-induced proliferation of endothelial cells and increased the survival of endothelial cells. The survival of primary cells obtained from glioma specimens was also enhanced in the presence of CXCL12. We point out the presence and the release of CXCL12 in tumor microenvironment and we observed a modulating effect of CXCL12 on proliferation and survival of both endothelial and tumoral cells. Our data support in vivo studies suggesting a role in angiogenesis played by CXCL12, which could represent a possible prognostic factor.

Brain Neoplasms↗
PubMed1997

E- and P-selectin are not involved in the recruitment of inflammatory cells across the blood-brain barrier in experimental autoimmune encephalomyelitis.

In experimental autoimmune encephalomyelitis (EAE) inflammatory cells cross the endothelial blood-brain barrier (BBB) and gain access to the central nervous system (CNS). Here we show that E- and P-selectin are not involved in the recruitment of inflammatory cells across the BBB. Neither expression of E- nor P-selectin is induced in BBB-forming endothelium at any time after initiation of EAE. Some of the inflammatory cells present in the CNS during EAE express ligands for E- or P-selectin. However, anti-E- and P-selectin antibodies influence neither immigration of inflammatory cells across the BBB nor the development of EAE. In general, suppression of E- and P-selectin expression on BBB endothelium is dependent on factors derived from the CNS microenvironment, eg, astrocytes. Our results suggest that during EAE suppression of E- and P-selectin expression on the BBB provides a CNS-specific mechanism to reduce leukocyte recruitment into the CNS.

Animals↗
PubMed1994

Voltage-dependent ion channels in glial cells.

Glial cells, although non-excitable, express a wealth of voltage-activated ion channels that are typically characteristic of excitable cells. Since these channels are also observed in acutely isolated cells and in brain slices, they have to be considered functional in the intact brain. Numerous studies over the past 10 years have yielded detailed characterizations of glial channels permitting comparison of their properties to those of their neuronal counterparts. While for the most part such comparisons have demonstrated a high degree of similarity, they also provide evidence for the expression of some uniquely glial ion channels. An increasing number of studies indicate that the expression of "glial" channels is influenced by the cells' microenvironment. For example, the presence of neurons can induce or inhibit (depending on the preparation and type of channel studied) the expression of glial ion channels. Like ion channels in excitable cells, glial channels can be functionally regulated by activation of second-messenger pathways, allowing for short-term modulation of their membrane properties. Although the extent to which most of the characterized ion channels are involved in glial function is presently unclear, a growing body of data suggests that certain channels play an active role in glial function. Thus inwardly rectifying K+ channels in concert with delayed rectifying K+ channels are thought to be involved in the removal and redistribution of excess K+ in the brain, a process referred to as "spatial buffering". Glial K+ channels may also be crucial in modulating glial proliferation. Cl- channels and stretch-activated cation channels are believed to be involved in volume regulation. Na+ channels appear to be important in fueling the glial Na+/K(+)-pump, and Ca2+ channels are likely involved in numerous cellular events in which intracellular Ca2+ is a critical second messenger.

Animals↗
PubMed1995

Spin-spin relaxation of brain tissues in systemic lupus erythematosus. A method for increasing the sensitivity of magnetic resonance imaging for neuropsychiatric lupus.

OBJECTIVE: To correlate the spin-spin relaxation time (T2) of brain tissue in neuropsychiatric systemic lupus erythematosus (NPSLE) with the patient's clinical condition. METHODS: T2 values were determined in 54 SLE patients and 45 non-SLE controls at 1.5 Tesla, using intensity from multi-echo magnetic resonance (MR) images fitted to an exponential decay curve with rate-constant T2. RESULTS: The T2 of white matter was increased in SLE patients compared with controls (P = 0.01) and was increased in those patients who had previously experienced major NPSLE: Patients with acute diffuse neurologic manifestations (seizures, psychosis, coma) demonstrated a longer T2 of the gray matter (mean +/- SD 92.75 +/- 6.35 ms, n = 10) than did other SLE patients (mean +/- SD 79.61 +/- 5.04 ms, n = 44) (P = 0.02 by t-test), which suggests acute cerebral edema. The mean T2 values of reversible and nonreversible focal lesions were significantly different (P < 0.02), indicating different microenvironments and micropathology. CONCLUSION: Quantitative T2 measurement extends the utility and sensitivity of conventional MR imaging for evaluating NPSLE:

Adolescent↗
PubMed2004

CRBP-III:lacZ expression pattern reveals a novel heterogeneity of vascular endothelial cells.

Vascular endothelial cells are structurally and functionally heterogeneous. However, the molecular basis of this heterogeneity remains poorly defined. We used subtractive and differential screening to identify genes that exhibit heterogeneous expression patterns among vascular endothelial cells. One such gene is cellular retinol binding protein III (CRBP-III/Rbp7). Analysis of the lacZ knockin line for this gene (CRBP-III:lacZ) revealed a novel organ-specific vascular endothelial expression pattern. LacZ was expressed in vascular endothelial cells in heart, skeletal muscle, adipose tissues, thymus, and salivary gland. However, it was not detected in other tissues such as brain, liver, and lung. Furthermore, the expression within each organ was primarily restricted to small capillary endothelial cells, but could not be detected in larger vessels. This organ-specific vascular endothelial expression of CRPB:lacZ is relatively resistant to the changes of organ microenvironment. However, the level of expression can be modified by vitamin A deficiency. Therefore, our results provide novel molecular evidence for the heterogeneity of vascular endothelial cells.

Animals↗
PubMed1993

Cues intrinsic to the retina induce nAChR gene expression during development.

Recent studies of optic nerve regeneration in goldfish have indicated that the optic tectum plays an important role in modulating the induction of nicotinic acetylcholine receptor (nAChR) gene expression in regenerating retinal ganglion cells (Heiber, Agranoff, and Goldman, 1992, J. Neurochem. 58:1009-1015). These observations suggest that induction of these genes is regulated by brain target regions. The appearance of nAChR mRNA in the developing rat retina coincides with a time when ganglion cells are sending axons to their brain targets (Hoover and Goldman, 1992, Exp. Eye Res. 54:561-571). Might a mechanism similar to that seen during goldfish optic nerve regeneration also mediate induction of nAChR gene expression during development of the mammalian retina? This possibility was tested by either transplanting embryonic rat retina to different brain regions, or explanting it to organ culture and assaying for nAChR gene expression. These studies showed that induction of the nAChR genes in developing rat retina is independent of the environment in which the retina develops. These results indicate that either the retinal microenvironment or a signal intrinsic to the retinal ganglion cell is responsible for this induction.

Animals↗
PubMed1992

Staining of hyaluronan in rat cerebellum with a hyaluronectin-antihyaluronectin immune complex.

The presence of hyaluronan was studied histochemically in the adult rat cerebellum. We used the hyaluronectin--antihyaluronectin immune complex technique based on the high affinity of hyaluronectin for hyaluronan. The immune complex was prepared with hyaluronectin from a human brain extract and an anti-hyaluronectin monoclonal antibody, which does not react with rat hyaluronectin. This is a specific probe for detecting hyaluronan in rat tissues without any reaction for tissue hyaluronectin. Hyaluronan was found at the nodes of Ranvier, in the perineuronal microenvironment of the deep nuclei and at the Purkinje cells surrounding the initial segment of the axon. It was located at the same places as hyaluronectin, in areas specialized in ion exchanges and neurotransmission. This suggests that the hyaluronectin-hyaluronan complex could be involved in these processes. The immune complex technique with anti-hyaluronectin monoclonal antibody thus seems to be a specific and valuable tool for investigations of the distribution of hyaluronan in the rat cerebellum.

Animals↗
PubMed2006

Transplantation of cultured progenitor cells to the mammalian retina.

Multipotent progenitor cells have now been isolated from the brain and retina, expanded in culture, and transplanted to the central nervous system (CNS). Work in rodent models has shown that progenitor cells derived from the CNS readily engraft in the diseased retina of mature recipients, where they develop morphologies appropriate to the local microenvironment and express mature markers, including the photoreceptor protein rhodopsin. There is also evidence for graft-associated rescue of host photoreceptors and preservation of light sensitivity in the degenerating retina. Graft survival does not necessarily require immune suppression, as CNS progenitors can behave as an immunoprivileged cell type. The use of biodegradable polymers results in an organised implant and further improves graft survival. Efforts are underway at present to extend this work to the pig, with initial results showing engraftment in both the neural retina and retinal pigment epithelium (RPE).

Absorbable Implants↗
PubMed1987

Thermodynamic analyses of pirenzepine binding to membrane-bound and solubilized muscarinic receptors from rat forebrain and heart.

The thermodynamic properties of pirenzepine (PZ) binding to membrane-bound and digitonin-solubilized muscarinic receptors (mAChR) from the rat forebrain and heart were evaluated. Apparent dissociation constants (Kd) of PZ were measured from saturation studies using [3H]PZ for forebrain membrane-bound mAChR and from inhibition studies of (-)-[3H]quinuclidinyl benzilate binding using unlabeled PZ, at five different temperatures from 4 degrees C to 37 degrees C. The Kd values of PZ binding to both membrane-bound and solubilized mAChR decreased with decreasing temperature whereas the maximum receptor density was unchanged. The heterogeneity of membrane-bound mAChR characterized by PZ binding to mAChR from both tissues disappeared upon digitonin-solubilization of the mAChR. The magnitude of changes of the Kd values with temperature was greater in the solubilized mAChR, suggesting that some constituents in the membrane constrained the affinity changes. The Gibbs free energy of PZ binding to membrane-bound and solubilized mAChR were both negative. The Gibbs free energy for membrane-bound receptors decreased (more negative) whereas those for solubilized receptors increased (less negative) with increasing temperature. The change in entropy was the apparent major driving force for PZ binding to membrane-bound receptors with the change in enthalpy also being favorable. The change in enthalpy was the apparent major driving force for PZ binding to solubilized receptors at all temperatures with the change in entropy being unfavorable above 17 degrees C in the rat forebrain mAChR and above 10 degrees C in the heart mAChR. Our results suggest an important role for the biomembrane microenvironment and possible topographical differences in the binding sites which may contribute to the mechanism of muscarinic subtypes.

Animals↗