Search PubMed⌕ Search

Biomedical subjects

C Kaur

Publications and source records attributed to C Kaur.

At least 19 recordsLinked to original sources
PubMed2003

Response of neurons and microglia/macrophages in the area postrema of adult rats following exposure to hypobaric hypoxia.

The response of neurons and microglia/macrophages in the area postrema (AP) was examined in adult rats following exposure to hypobaric hypoxia. In this connection, immunoexpression of complement type 3 (CR3) receptors, major histocompatibility complex (MHC) class I and II antigens and ED1 antigens on the macrophages/microglia was downregulated immediately after the hypoxic insult. However, it showed an upregulation at 7-14 days and was comparable to the controls thereafter. At the ultrastructural level, swollen axons showing disruption of their myelin sheaths were observed between 7 and 14 days. At this time interval microglia/macrophages in the AP were observed to phagocytose such axons. Neurons did not show any structural alteration at any time interval following hypoxic exposure and appeared comparable to the neurons in the control AP. It is suggested that alterations in CR3 receptors, ED1, and MHC I and II antigens on the macrophages/microglia in hypobaric hypoxia were in response to axonal changes. Increased permeability of blood vessels following hypoxia may also play a role in activation of these cells as they would be involved in the clearance of extravasated serum derived substances.

Animals↗
PubMed2003

Induction of inducible nitric oxide synthase expression in activated microglia following domoic acid (DA)-induced neurotoxicity in the rat hippocampus.

Neuronal degeneration followed by glial activation (microglia and astrocytes) and nitric oxide synthase (NOS) expression in the hippocampus was investigated at 3 months after domoic acid (DA) administration and compared with DA treated rats at 5 days time interval which was reported earlier. Massive degeneration with complete absence of neurons in the hippocampal CA1 and CA3 regions and hypertrophied microglial cells showing intense immunoreaction with the antibody OX-42 was observed at 3 months after DA administration. Sparsely distributed OX-42 positive microglial cells were observed in the hippocampus of control rats at 3 months after saline treatment No apparent changes could be observed in the immunoreactivity of GFAP at 3 months after saline and DA administration. Neuronal nitric oxide synthase immunoreactive neurons were completely absent in the hippocampus at 3 months after DA administration. In contrast, nicotinamide adenine dinucleotide phosphate diaphorase (NADPH-d) histochemical analysis revealed absence of NADPH-d reactivity in the neurons, but positive reactivity in the microglial cells of CA1-CA3 regions in the hippocampus after DA treatment. Double immunofluorescense revealed co-expression of inducible nitric oxide synthase with immunoreactive OX-42 positive microglial cells in the hippocampal subfields at 3 months after DA administration. The microglia-produced NO appears to be a secondary phenomenon in the prolonged inflammatory process following DA-induced neuronal degeneration.

Animals↗
PubMed2003

Distribution of NADPH-diaphorase and expression of nNOS, N-methyl-D-aspartate receptor (NMDAR1) and non-NMDA glutamate receptor (GlutR2) genes in the neurons of the hippocampus after domoic acid-induced lesions in adult rats.

Neuronal degeneration followed by detection of nitric oxide (NO)-producing neurons of the hippocampus was investigated at 4 h, 16 h, 24 h, 2 days, 5 days, and 14 days after administration of domoic acid (DA), in the present study. Histopathological analysis (Nissl staining) displayed dark-stained degenerating neurons in the hippocampus at 24 h to 14 days after DA administration, with degeneration most severe at 5-14 days. NADPH-d-positive neurons were observed in different subfields of the hippocampus in control rats and DA treated rats at 4-24 h. Complete loss of NADPH-d-positive neurons in the CA1 and CA3 subfields and also in the hilus of dentate gyrus (DG) was observed at 5 days and 14 days after the administration of DA. In contrast, at 4-24 h, neuronal nitric oxide synthase (nNOS)-immunoreactive cells were absent from the hippocampal subfields in control and DA-treated animals but were observed at 5 days and 14 days after DA administration. N-methyl-D-aspartate receptor (NMDAR1) immunoreactivity was increased in the hippocampal neurons at 5 days after DA administration and double immunofluorescence demonstrated its coexpression with induced nNOS expression. No significant change could be observed in the immunoreactivity of non-NMDA receptor (GlutR2) as compared with the controls, while occasional immunoreactive neurons were colocalized with induced nNOS expression. Reverse transcription-polymerase chain reaction analysis showed the upregulated expression of nNOS and downregulated expression of NMDAR1 at 5 days after the administration of DA. Although nNOS mRNA expression was rapidly induced at 5 days after DA administration, in situ hybridization analysis revealed complete loss of nNOS mRNA expression in the region of neuronal degeneration in the hippocampus at 24 h and 5 days after DA administration. The present study has shown that NADPH-d and nNOS express differentially in the neurons of the hippocampus in DA-induced neurotoxicity. It is speculated that induction of nNOS and glutamate receptor genes in the neurons of the hippocampus in response to DA-induced neurotoxicity could have contributed to the neuronal degeneration.

Animals↗
PubMed2003

Protective role of melatonin in domoic acid-induced neuronal damage in the hippocampus of adult rats.

Domoic acid (DA), a kainite-receptor agonist and potent inducer of neurotoxicity, has been administered intravenously in adult rats in the present study (0.75 mg/kg body weight) to demonstrate neuronal degeneration followed by glial activation and their involvement with inducible nitric oxide synthase (iNOS) in the hippocampus. An equal volume of normal saline was administered in control rats. The pineal hormone melatonin, which protects the neurons efficiently against excitotoxicity mediated by sensitive glutamate receptor, was administered intraperitoneally (10 mg/kg body weight), 20 min before, immediately after, and 1 h and 2 h after the DA administration, to demonstrate its role in therapeutic strategy. Histopathological analysis (Nissl staining) demonstrated extensive neuronal damage in the pyramidal neurons of CA1, CA3 subfields and hilus of the dentate gyrus (DG) in the hippocampus at 5 days after DA administration. Sparsely distributed glial fibrillary acidic protein (GFAP)-immunoreactive astrocytes were observed in the hippocampus at 4-24 h after DA administration and in the control rats. Astrogliosis was evidenced by increased GFAP immunoreactivity in the areas of severe neuronal degeneration at 5 days after DA administration. Along with this, microglial cells exhibited an intense immunoreaction with OX-42, indicating upregulation of complement type 3 receptors (CR3). Ultrastructural study revealed swollen or shrunken degenerating neurons in the CA1, CA3 subfields and hilus of the DG and hypertrophied astrocytes showing accumulation of intermediate filament bundles in the cytoplasm were observed after administration of DA. Although no significant change could be observed in the mRNA level of iNOS expression between the DA-treated rats and controls at 4-24 h and at 5-day time intervals, double immunofluorescense revealed co-expression of induced iNOS with GFAP immunoreactive astrocytes, but not in the microglial cells, and iNOS expression in the neurons of the hippocampal subfields at 5 days after DA administration. Expression of iNOS was not observed in the hippocampus of control rats. DA-induced neuronal death, glial activation, and iNOS protein expression were attenuated significantly by melatonin treatment and were comparable to the control groups. The results of the present study suggest that melatonin holds potential for the treatment of pathologies associated with DA-induced brain damage. It is speculated that astrogliosis and induction of iNOS protein expression in the neurons and astrocytes of the hippocampus may be in response to DA-induced neuronal degeneration.

Animals↗
PubMed2002

Dexamethasone induces dendritic alteration but not apoptosis in the neurons of the hippocampus in postnatal rats.

One day old rats received daily injections of dexamethasone and were sacrificed 24 h after the 1st and 7th injections. Neuronal death by apoptosis in the hippocampus was investigated by immunohistochemistry using bcl2, bax and caspase3 antibodies. The immunoreactivity expressed by the pyramidal neurons and the dentate granule cells with these antibodies was comparable in the dexamethasone treated and control rats injected with saline. At the ultrastructural level, the dendrites showed vacuolation indicative of degeneration in the dexamethasone administered rats. Results of reverse transcriptase-polymerase chain reaction analysis showed that bcl2 and bax mRNA was constitutively expressed in the hippocampus of control rats and showed no significant change in the dexamethasone treated rats. The results of this study indicate that dexamethasone induces degeneration of the dendrites but does not induce neuronal apoptosis in the hippocampus of postnatal rats.

Animals↗
PubMed2002

Plasma melatonin, pinealocyte morphology, and surface receptors/antigen expression on macrophages/microglia in the pineal gland following a high-altitude exposure.

The present study examined the effects of high-altitude exposure on the pineal gland, the main source of production of melatonin. It was surmised that hypoxia experienced at high altitude, caused by decreased oxygen tension in the ambient air, might lead to some structural alterations in the pineal gland and, hence, affect its melatonin production. Adult Wistar rats were exposed to an altitude of 8,000 m for 2 hr in an altitude chamber and then sacrificed at various time intervals after the exposure. Normal rats kept at ground level were used as controls. Blood samples were collected at various time intervals for measurement of plasma melatonin level, and the pineal glands from both groups were processed for electron microscopy and immunohistochemistry. The plasma melatonin level showed a steady increase following altitude exposure peaking at 7 days and returned to control levels thereafter. Between 1 and 4 days after altitude exposure, the mitochondrial number and lipid droplets in the pinealocytes appeared to be reduced compared with those in control rats. At 7 days, however, the mitochondrial numbers and lipid droplets were noticeably increased. At the same time interval, the expression of complement type 3 receptors and major histocompatibility class II antigens as detected with the antibodies OX-42 and OX-6, respectively, in macrophages/microglia was up-regulated compared with that in the control rats and those killed at earlier times. This was attributed to the increased serum melatonin after the altitude exposure. By 14 and 21 days, the ultrastructure of pinealocytes and immunoreactivity of macrophages/microglia were comparable with those in the control rats. We conclude from this study that an altitude exposure in rats leads to an increase in melatonin production, which returned to control levels with passage of time.

Altitude Sickness↗
PubMed2002

Upregulation of adrenocorticotrophic hormone in the corticotrophs and downregulation of surface receptors and antigens on the macrophages in the adenohypophysis following an exposure to high altitude.

Altitude exposures lead to the development of hypobaric hypoxia because of low oxygen tension in the ambient air. This study has shown the vigorous upregulation of adrenocorticotrophic hormone (ACTH) expression in corticotrophs of the pars distalis (adenohypophysis) of rats 1-7 days after an altitude exposure. Concomitant to this was the increase in number and hypertrophy of the immunoreactive corticotrophs. It was suggested that this had resulted in an upsurge of ACTH production which may have suppressed the immuno-expression of complement type 3 receptors and major histocompatibility complex class II antigens constitutively expressed by the parenchymal macrophages through paracrine action. Along with ACTH, altered levels of other hormones following such exposures may also contribute to suppression of antigen presenting function and phagocytic activity of macrophages. The effects of altitude (hypobaric hypoxia) exposure, however, were reversible as the above immunohistochemical changes returned to normal 21-28 days after the hypobaric hypoxic insult.

Adrenocorticotropic Hormone↗
PubMed2001

Domoic acid-induced neuronal damage in the rat hippocampus: changes in apoptosis related genes (bcl-2, bax, caspase-3) and microglial response.

Domoic acid (DA), a potent neurotoxin, administered intravenously (0.75 mg/kg body weight) in adult rats evoked seizures accompanied by nerve cell damage in the present study. Neuronal degeneration and microglial reaction in the hippocampus were investigated, and the temporal profile of bcl-2, bax, and caspase-3 genes in cell death or survival was assessed following the administration of DA. Nissl staining showed darkly stained degenerating neurons in the hippocampus following the administration of DA at 1-21 days, the degeneration being most severe at 5 days. Ultrastructural study in CA1 and CA3 regions of hippocampus revealed two types of neuronal degeneration, cells that exhibited swollen morphology and shrunken electron-dense cells. Immunoreactivity of Bcl-2 and Bax was increased considerably at 16 hr and 24 hr in the neurons of the hippocampus following DA administration. No significant change was observed in the immunoreactivity of caspase-3 in the controls and DA-treated rats at any time interval. Microglial cells in the hippocampus showed intense immunoreaction with the antibodies OX-42 and OX-6 at 1-21 days after DA administration, indicating the up-regulation of complement type 3 receptors and major histocompatibility complex type II antigens for increased phagocytic activity and antigen presentation, respectively. Terminal deoxynucleotidyl-transferase-mediated dUTP nick end labeling (TUNEL) showed occasional positive neurons in the CA1 and CA3 regions at 5 days after DA administration, with no positive cells in the controls. RT-PCR analysis revealed that bcl-2 and bax mRNA transcripts in the hippocampus were significantly increased at 16 hr and gradually decreased at 24 hr following the administration of DA. Although bax and bcl-2 mRNA expression is rapidly induced at early stages, in situ hybridization analysis revealed complete loss of bcl-2, bax, and caspase-3 mRNA at 24 hr after DA administration in the region of neuronal degeneration in the hippocampus. These results indicate that the pattern of neuronal degeneration observed during DA-induced excitotoxic damage is mostly necrotic.

Animals↗
PubMed2001

Origin of microglia.

This paper reviews the various proposed hypotheses on the origin of microglia. The seminal study of del Rio-Hortega first stated that the cells were derived from the mesodermal pial cells that invaded the brain during embryonic development. Along with this was the description of precursor cells in the yolk sac in early development. Our results in the embryonic mouse brain have shown the occurrence of lectin-labelled precursor cells at the yolk sac that later appeared in the mesenchymal tissue associated with the neuroepithelium where they penetrated the nervous tissue to become the microglia. A second major view has held that microglia are of neuroectodermal origin; the cells either originate from glioblasts or the germinal matrix. Another school of thought is that microglia are derived from blood monocytes. In this connection, circulating monocytes enter the developing brain to assume the form as amoeboid microglia that subsequently evolve to become the ramified microglia. In traumatic brain lesions following an intravenous injection of colloidal carbon as a cytoplasmic marker for monocytes, it was found that carbon-labelled monocytes were the main source of brain macrophages, some of which transformed into microglia during the healing process. In conclusion, our results derived from the normal and altered brain development as well as from experimental lesions tend to favour the view of the monocytic nature of microglia. Recent studies by us also point to the possibility that some microglial cells may arise from the pial mesenchymal macrophages that appear to originate from the yolk sac precursors.

Animals↗
PubMed2001

Heterogeneities in supercooled liquids: a density-functional study.

A metastable state, characterized by a low degree of mass localization, is identified using density-functional theory (DFT). This free energy minimum, located through the proper evaluation of competing terms in the free energy functional, is independent of the specific form of the DFT used. Computer simulation results on particle motion indicate that this heterogeneous state corresponds to the deeply supercooled state.

Journal Article↗
PubMed2001

Choroid plexus epithelial cells in adult rats show structural alteration but not apoptosis following an exposure to hypobaric hypoxia.

The choroid plexus in adult rats was examined for any structural alteration or apoptotic cell death following a high altitude exposure which leads to the development of hypobaric hypoxia due to reduced oxygen tension in the atmospheric air. Caspase-3 (a protease which mediates apoptosis) immunoreactivity was absent in the choroid plexus epithelial cells in the control rats and following altitude exposure; Bcl-2 (anti-apoptotic protein) and Bax (pro-apoptotic protein) immunoreactivity were upregulated at 3 h-2 days following the altitude exposure when compared to the controls but not in longer surviving rats. At the ultrastructural level, glycogen particles and vacuoles were observed in some epithelial cells at 7 days following the altitude exposure. It is suggested that transient exposure to high altitude may not cause much damage to the choroid plexus epithelial cells except for some structural alteration which may be due to altered metabolism of the cells in response to hypobaric hypoxia.

Age Factors↗
PubMed2001

Expression of Fos immunoreactivity in some catecholaminergic brainstem neurons in rats following high-altitude exposure.

This study examined the response of neurons of the cardiorespiratory centers, i.e., the nucleus tractus solitarius and the ventrolateral medulla as well as the area postrema in adult and postnatal rats subjected to high-altitude exposure at 4,000 m and 8,000 m. In adult control rats, sporadic Fos-positive neurons were detected in the above-mentioned areas. On exposure to 4,000 m altitude, the number of Fos-positive neurons was noticeably increased. At 8,000 m, the incidence of labeled cells was markedly increased, with many of them doubly labeled for tyrosine hydroxylase. In postnatal rats, Fos expression was not detected in these areas in either control rats or rats exposed to 4,000 m altitude. Fos-positive cells, however, were observed in the these areas in postnatal rats exposed to 8,000 m. In the latter, tyrosine hydroxylase labeling was observed in some Fos-positive cells in the nucleus tractus solitarius and ventrolateral medulla. In rats killed at 24 hr after exposure to high altitude, Fos expression in both the adult and the postnatal rats was comparable to that in their corresponding control rats. Present results suggest that Fos expression in various brainstem areas was induced by reduced oxygen tension in the ambient air at high altitude. Double labeling of some Fos-positive neurons with tyrosine hydroxylase indicates an increased sympathetic activation, which may be involved in the mediation of cardiorespiratory responses to hypoxia. This, however, was less evident in the postnatal animals. It is possible that the peripheral chemoreceptors or the regulation of autonomic functions is not fully developed in this age group.

Altitude Sickness↗
PubMed2001

Plasma cell mucositis.

A case of plasma cell mucositis is described for its rarity. A probable aetiological correlation with periodontitis is discussed. The patient showed good response to intralesional and topical steroids.

Clobetasol↗
PubMed2001

Cellular inflammatory response associated with breakdown of the blood-brain barrier after closed head injury in rats.

This study reports a widespread microglial response characterized by an upregulation of surface antigens, such as complement type 3 receptors (CR3) and major histocompatibility complex (MHC) class II antigens on these cells following closed head injury. Increased expression of CR3 (OX-42) and MHC class II antigens (OX-6) was observed in rats killed at 1, 3, and 5 days after injury. Intense OX-42 immunoreactivity was observed in microglial cells throughout the brain with a smaller number of them being OX-6 positive. In addition to microglial reaction, astrocytic activation reflected in cellular hypertrophy and increased immunoreactivity for glial fibrillary acidic protein (GFAP) was observed at 5 days after head injury. Together with the above, a diffuse perivascular and intraneuronal immunostaining for immunoglobulin G (IgG) was observed primarily in the cerebral cortex. This was accompanied by an enhanced expression of both endothelial nitric oxide synthase (eNOS) in blood vessels and inducible nitric oxide synthase (iNOS) in brain macrophages. In rats subjected to closed head injury followed by a single intraperitoneal (i.p.) injection of rhodamine isothiocyanate (RhIc), seepage of the fluorescent dye into the neuropil was observed. This had resulted in the labelling of the cortical neurons clearly demonstrating a breakdown of the blood-brain barrier (BBB). In the latter, it is conceivable that the ensuing leakage of plasma immunoglobulins and other serum-derived materials could induce the expression of MHC class II antigens on microglia. The mechanism causing the BBB dysfunction is not clear, although present results suggest that excessive release of nitric oxide (NO) may be a contributory factor. The widespread activation of microglia in rats after head injury suggests their involvement in increased endocytosis and immunological responses.

Animals↗