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Biomedical subjects

C Kaur

Publications and source records attributed to C Kaur.

At least 55 records · Page 3Linked to original sources

Effects of chloroquine on the ependyma, choroid plexus and epiplexus cells in the lateral ventricles of rats.

1-day-old postnatal rats were given daily intraperitoneal injections of chloroquine for 6 successive days and sacrificed at 7, 14 and 21 days of age. In rats killed at 7 and 14 days of age, the choroid plexus epithelial cells and ependymal cells lining the lateral ventricles showed a marked increase in number and size of lysosomes; some cells were extremely vacuolated. The epiplexus cells associated with the choroid plexus were also affected showing numerous vacuoles and lamellar bodies. Furthermore, their immunoreactivity with the antibodies OX-42, OX-18, OX-6 and ED1 were augmented when compared with cells in the control rats. At 21 days of age the ultrastructural features of the various cell types in the chloroquine-injected rats resembled those in the corresponding control rats. The immunoreactivity of epiplexus cells was also comparable in the two groups of animals at this time point. It is concluded from this study that although chloroquine induces acute structural alterations of choroid plexus epithelial cells, ependymal cells and epiplexus cells, its effects are reversible since the cells regained their normal ultrastructure and immunohistochemical features following the discontinuation of the drug.

Animals↗

Ultrastructural changes of macroglial cells in the rat brain following an exposure to a non-penetrative blast.

The present study examined the ultrastructural changes in astrocytes and oligodendrocytes in rats following an exposure to a non-penetrative blast. At 1 and 7 days after the blast, the astrocytes in the cerebral and cerebellar cortex were hypertrophied; their end-feet associated with the blood vessels were also swollen, bearing sparsely distributed organelles. The above changes were not observed in experimental rats when the survival interval was prolonged. It is concluded from this study that the blast could have disrupted the integrity of the blood-brain barrier resulting in possible abnormal entry of serum-derived substances thereby leading to astrocytic hypertrophy. The reversible nature of the changes is evidenced by the seemingly normal appearance of astrocytes in rats killed at 14, 21 and 28 days after the blast. Oligodendrocytes remained unaffected at various time intervals after the blast.

Animals↗

Studies of the choroid plexus and its associated epiplexus cells in the lateral ventricles of rats following an exposure to a single non-penetrative blast.

The choroid plexus in rats exhibited ultrastructural changes following a non-penetrative blast. The immunophenotypic features of epiplexus cells associated with the choroid plexus epithelium were also altered. In rats killed at 1 and 7 days after the blast, the intercellular spaces between the epithelial cells were greatly widened, coupled with the massive eruption and possible extrusion of the apical cytoplasm into the ventricular lumen. Associated with these changes was the passage of some monocytes/lymphocytes across the epithelium. The incidence of such a migratory phenomenon was more frequent in rats killed 7 days after the blast. In rats killed 14 days after the blast, the ultrastructural changes of the epithelial cells became less pronounced. At 21 and 28 days after the blast, the ultrastructure of the choroid plexus was comparable to that of normal specimens. The immunoreactivity of epiplexus cells in terms of their cell number and staining intensity with the monoclonal antibodies OX-42, OX-18, OX-6 and ED1 was noticeably augmented at 7 and 14 days after the blast; this, however subsided at 21 and 28 days. It is concluded that the choroid plexus is extremely sensitive to a blast wave as manifested by its structural alterations and the vigorous expression of CR3 receptors and MHC antigens by the epiplexus cells. It is suggested that a possible immune response might have been triggered in the cerebrospinal fluid ventricular system following the blast.

Animals↗

An immunohistochemical study of the intraventricular macrophages in induced hydrocephalus in prenatal rats following a maternal injection of 6-aminonicotinamide.

Hydrocephalus was induced experimentally in prenatal rats following an injection of 6-aminonicotinamide (6-AN) into pregnant rats. The most remarkable change of the dilated lateral ventricles was in a marked increase in the number of intraventricular macrophages, some of which were laden with ingested erythrocytes. The immunoreactivity of the intraventricular macrophages was noticeably enhanced with the monoclonal antibodies OX-42 and OX-18 which marked the complement type 3 receptors (CR3) and major histocompatibility complex (MHC) class I antigen, respectively. Many immunoreactive cells with similar external morphology were observed to penetrate the ependymal lining at the roof of the ventricles. This, coupled with the concomitant depletion of the conglomeration of amoeboid microglia in the supraventricular corpus callosum, suggests that the upsurge of immunoreactive intraventricular macrophages in hydrocephalus was partly due to the influx of amoeboid microglia probably in response to the damage of the ventricular walls and possible alteration in the contents of the cerebrospinal fluid. The significance of the upregulation of complement type 3 receptors and major histocompatibility complex class I antigens on epiplexus cells in hydrocephalic rats remains to be explored, although our results suggest that the surface antigens may be involved in increased phagocytosis and/or a possible immune response.

6-Aminonicotinamide↗

Response of amoeboid microglial cells to chloroquine injections in postnatal rats.

One-day-old postnatal rats were given single daily intraperitoneal injections of chloroquine for 6 successive days and sacrificed at 7, 14 and 21 days of age. In rats killed at 7 days of age, the amoeboid microglial cells in the corpus callosum above the lateral ventricles showed a marked increase in vacuoles and lysosomes by electron microscopy. Immunohistochemical study showed that the number and OX-42 immunoreactivity of these cells were comparable to those of the control rats. At 14 days, the immunoreactive amoeboid microglia appeared hypertrophic and their immunoreactivity was noticeably enhanced when compared with the ramified cells in the controls. Ultrastructurally the amoeboid microglial cells in the chloroquine-treated cells showed massive lysosomes. At 21 days, the immunoreactivity of amoeboid microglial cells and their lysosomes were comparable to those of the controls. Results with the antibodies ED1 and OX-18 paralleled those with OX-42 in terms of the temporal change of immunoreactivity and external morphology of amoeboid microglia. OX-6 immunoreactive cells were not observed in both groups of rats. With the isolectin, Griffonia simplicifolia, the reaction product which was normally confined to the plasma membrane of amoeboid microglia was also localized in vacuoles and the massive lysosomes in the chloroquine-injected rats suggesting the internalization of plasma membrane and its sequestration in the lysosomes. It is concluded from this study that although amoeboid microglial cells responded vigorously to chloroquine, its effects are reversible since with the discontinuance of the drug and prolongation of survival interval, the cells regained their normal features.

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Histochemical demonstration of nitric oxide synthase-like immunoreactivity in epiplexus cells and choroid epithelia in the lateral ventricles of postnatal rat brain induced by an intracerebral injection of lipopolysaccharide.

The present in vivo study showed the expression of nitric oxide synthase-like immunoreactivity in epiplexus cells in the lateral ventricles induced by intracerebral injection of lipopolysaccharide into postnatal rats. Nitric oxide synthase-like immunoreactivity was vigorously expressed in epiplexus cells 1 and 3 days after the lipopolysaccharide injection, but by 7 days post-injection, it became undetectable. The expression of nitric oxide synthase-like immunoreactivity was also observed in some of the choroid epithelial cells. The nitric oxide synthase-like immunoreactivity in these cells appeared to be more intense in the ventricle ipsilateral to the LPS injection than that on the contralateral side. The immunostaining patterns of OX-42 and OX-6 for the detection of complement type 3 receptors and major histocompatibility complex class II antigens respectively paralleled that of anti-nitric oxide synthase, indicating that lipopolysaccharide-induced nitric oxide synthase-like immunoreactivity was primarily in epiplexus cells. Immunoelectron microscopy revealed that the nitric oxide synthase-like immunoprecipitate in epiplexus cells and choroid epithelial cells filled the entire cytoplasm and in some areas associated with the membranes of some of the organelles especially the mitochondria, suggesting that the enzyme is mainly cytosolic. It is speculated that nitric oxide synthase in these cells is involved in the synthesis of nitric oxide. The nitric oxide production, if any, through the enzymatic activity of nitric oxide synthase in epiplexus cells as well as the choroid epithelial cells may be involved in host defense against bacterial endotoxin in the ventricular system of postnatal rat brain.

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Effects of dexamethasone on the epiplexus cells in postnatal rats.

The epiplexus cells in postnatal rats were markedly reduced in number and immunoreactivity for OX-42, OX-18 and ED1 following subcutaneous injections of dexamethasone. This was especially evident in rats receiving two or three successive injections of dexamethasone and killed at the age of 4 or 7 days. At 14 and 21 days, the cells did not exhibit any striking difference from their corresponding controls in terms of cell number and immunoreactivity for the above antibodies. Occasional epiplexus cells were labelled with the antibody OX-6 in both groups of rats sacrificed at different time points. In rats receiving dexamethasone coupled with rhodamine isothiocyanate (RhIc), the epiplexus cells, though fewer in number than the corresponding controls, emitted bright fluorescence. It is concluded that the reduction of epiplexus cells following dexamethasone injections is due to the suppression of their precursor cells, i.e. monocytes. The phagocytic activity of the persisting epiplexus cells did not appear to be abolished by dexamethasone as evidenced by their uptake of RhIc. Our results suggest that the effects of dexamethasone are reversible.

Animals↗

The response of neurons and microglia to blast injury in the rat brain.

Rats subjected to a single non-penetrative blast were examined for possible neuronal damage and glial reaction by immunohistochemistry and electron microscopy. The most dramatic feature in rats killed between 1 and 14 days after the blast was the widespread response of microglial cells in various parts of the brain in which the cells were hypertrophied and their surface antigens, like complement type three receptors (CR3), were upregulated. The blast wave also induced the vigorous expression of major histocompatibility complex (MHC) class I and II (Ia) antigen. In rats killed 21 days after the blast, the elevated immunoreactivity of microglia had subsided and at 28 days both the microglial external morphology and immunoreactivity were comparable to those of normal animals. In rats killed 4-7 days after the blast, the neurons in the cerebral and cerebellar cortex appeared normal except for the occurrence of some 'darkened' dendrites. The incidence of 'darkened' dendrites was most common in rats killed at day 14 but they were absent at 21 and 28 days. Microglial cells were closely associated with some of the 'darkened' dendrites. Results in this study show that a non-penetrative blast in rats provokes a widespread microglial activation suggesting increased endocytosis and immunological responses. However, it remains uncertain whether such a drastic response was a direct activation of the cells by the blast wave or elicited indirectly by some chemical factors released from the damaged brain tissues.

Animals↗

Transient expression of transferrin receptors and localisation of iron in amoeboid microglia in postnatal rats.

The expression of transferrin receptors marked by the monoclonal antibody OX-26 and the localisation of iron were studied in amoeboid microglial cells in postnatal rats. Transferrin receptors were vigorously expressed in amoeboid microglia in rats ranging from 1 to 10 d of age but were undetectable in older rats. Thin serial sections showed that the OX-26 positive amoeboid microglial cells were also immunoreactive for OX-42 and ED1. Using Perls' medium, this study showed the presence of a considerable amount of iron in amoeboid microglial cells in 1-10 d rats. Most iron-containing cells were round but their number had diminished by 2 and 3 wk of age, when the iron was localised instead in some branched cells which were identified as either oligodendrocytes or ramified microglia cells. There has been much speculation on the functional significance of transferrin receptors on amoeboid microglia in postnatal rats. It is suggested that the receptors facilitate the acquisition of iron necessitated for various functions of amoeboid microglia in the developing brain. The presence of iron in some oligodendrocytes suggests their involvement in mediating iron mobilisation and storage. Its localisation in some ramified microglia in older rats indicates the possible role of these cells in sequestration and detoxification of iron in the central nervous system.

Aging↗

Expression and upregulation of transferrin receptors and iron uptake in the epiplexus cells of different aged rats injected with lipopolysaccharide and interferon-gamma.

The expression of transferrin receptors marked by the monoclonal antibody OX-26 and localisation of iron was studied in epiplexus cells in the lateral ventricles of different aged rats subjected to the challenge of the bacterial toxin, lipopolysaccharide, and treatment with interferon-gamma. Transferrin receptor expression in epiplexus cells was extremely low in normal rats, but was vigorously elevated in rats receiving intraperitoneal injections of lipopolysaccharide (LPS); other antigens such as complement type 3 receptors immunostained with OX-42 and macrophage antigen marked by ED-1 were also notably augmented. After 6 successive intraperitoneal injections of interferon-gamma, the expression of transferrin receptors showed only a moderate increase. Using Perls' staining method, some iron-containing epiplexus cells were observed in early normal postnatal rats, but their number was markedly decreased with age. After LPS administration, a moderate increase in the number of iron-containing epiplexus cells was observed in different aged rats. The significance of the upregulation and vigorous expression of transferrin receptors on epiplexus cells is speculative. One possible explanation would be that they facilitate an increase in the acquisition of iron by these cells for storage, oxidative killing and/or immunological activation. The localisation of iron in the choroid plexus in the lateral ventricles suggests that the latter may function as an important storage organ for iron. Present results also suggest the presence of an efficient transport system for the transfer of iron across the interface of the blood and cerebrospinal fluid.

Aging↗

Up-regulation of surface antigens on epiplexus cells in postnatal rats following intraperitoneal injections of lipopolysaccharide.

Epiplexus cells in postnatal rats exhibited a remarkable up-regulation of major histocompatibility complex class I and II antigen expression after intraperitoneal administration of bacterial lipopolysaccharide; other surface antigens, i.e. complement type 3 receptors and leukocyte common antigens, were also vigorously elevated when compared with those of the corresponding control rats. The immunostaining of epiplexus cells with OX-42, OX-18 and OX-1 for the detection of complement type 3 receptors, major histocompatibility class I and leukocyte common antigens, respectively, was noticeably enhanced with a drastic increase in their numbers. The most significant finding was the upsurge of OX-6-positive epiplexus cells exhibiting major histocompatibility class II antigens, especially in rats receiving two intraperitoneal injections of lipopolysaccharide and killed at the age of 14 days. Immunoelectron microscopy confirmed the above findings and added the fact that the immunoreactive site was confined to the plasma membrane. An interesting feature was the occurrence of OX-6-positive macrophage-like cells in transit across the choroid epithelium. It is concluded from this study that the upsurge of immunopositive epiplexus cells after lipopolysaccharide injections was partly attributed to the infiltration of stromal macrophages which migrated across the epithelium. The up-regulation of major histocompatibility complex class I and II antigen expression on epiplexus cells by lipopolysaccharide would enable them to carry out self-recognizing and antigen-presenting function in the ventricular system.

Animals↗

A case report on radiotherapy in choriocarcinoma: a life saving procedure.

Radiation therapy was tried to control hemorrhage from uterine cavity in a case of choriocarcinoma in which surgery was not practically possible due to the presence of a large nodule extending from suburethral region up to anterior fornix involving the entire anterior vaginal wall and patient being in a very critical condition. Radiotherapy was found to be successful and life saving.

Adult↗

The effects of subcutaneous injections of glucocorticoids on amoeboid microglia in postnatal rats.

Subcutaneous injections of glucocorticoids into postnatal rats resulted in a drastic reduction in the number of amoeboid microglial cells in the corpus callosum as shown by their labelling with the monoclonal antibodies of the OX-series, ED1, lectin and rhodamine isothiocynate (RhIc). In rats receiving 2 or 3 injections of glucocorticoids and killed at the age of 4 or 7 days, between 40 to 60% of the callosal amoeboid microglial cells were depleted when compared with the corresponding control animals. The cells that survived the glucocorticoid treatments became ramified, while those in the controls of the same age group remained round or amoeboidic. In rats killed at 2 or 3 weeks of age, the microglia became extremely ramified with a concomitant diminution in their immunostaining, particularly in the glucocorticoid-injected rats. In rats receiving glucocorticoid injections along with RhIc, the RhIc-laden amoeboid microglia appeared round and amoeboidic and were intensely stained with OX-42, suggesting their activation and upregulation of complement type 3 receptors when compared with rats receiving only glucocorticoids. Compared with the control, cellular proliferation continued in rats given glucocorticoid injection as indicated by the occurrence of many bromodeoxyuridine-labelled cells in the corpus callosum at the age of 6 days. Ultrastructural studies confirmed the presence of mitotic cells identified as amoeboid microglia because of their labelling with isolectin. A striking ultrastructural feature in glucocorticoids-injected rats was the wide occurrence of amoeboid microglial cells that had ingested a variable number of lectin-labelled cells. It is concluded from this study that the drastic reduction of amoeboid microglia after glucocorticoid injections can be attributed to the suppression of their precursor cells, monocytes. Another possible explanation is the acceleration of their degeneration process, probably greatly enhanced by glucocorticoids; the degenerating amoeboid microglia were readily eliminated by the surviving amoeboid microglial cells through endocytosis. Glucocorticoids also accelerated the maturation process of the persisting amoeboid microglia to become ramified in form.

Animals↗

Immunophenotypic features of epiplexus cells and their response to interferon gamma injected intraperitoneally in postnatal rats.

The expression of major histocompatibility complex (MHC) antigens (class I and II), type 3 complement receptor (CR3) and leucocyte common antigen (LCA) was examined in epiplexus cells in rats of different ages. The cells exhibited intense immunoreactivity with the monoclonal antibody OX-42 which recognizes CR3 receptors. In early postnatal rats (1 d), the immunolabelled cells were mostly round but with increasing age (7 wk), they assumed a ramified or elongated form. The expression of LCA marked by the monoclonal antibody OX-1 followed a similar staining pattern. Class I MHC antigen expression was also demonstrated in some epiplexus cells using the monoclonal antibody OX-18 but they were less numerous than the OX-42 or OX-1 positive cells. Only sporadic OX-6 positive cells were observed in postnatal rats but they showed a marked increase in number in adult rats, suggesting an upregulation of class II MHC antigens with age. The expression of MHC class II antigens was vigorously elevated in postnatal rats receiving 6 successive intraperitoneal (i.p.) injections of interferon gamma (IFN-gamma). In these animals, a large number of intensely stained OX-6 positive epiplexus cells were observed. These were mostly elongated or ramified with long processes. The immunostaining of epiplexus cells with OX-18 was also enhanced after IFN-gamma injections but the expression of CR3 and LCA appeared to be unaffected. It is concluded that the expression of MHC class I and II antigens on epiplexus cells is upregulated and induced respectively after successive i.p. injections of IFN-gamma into postnatal rats.(ABSTRACT TRUNCATED AT 250 WORDS)

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Immunohistochemical and lectin-labelling studies of the distribution and development of microglia in the spinal cord of postnatal rats.

The present study describes the development and differentiation of microglial cells in the spinal cord of postnatal rats ranging from 1 day to 3 weeks of age. Using the monoclonal antibody OX-42, three different morphological forms of immunoreactive cells (SP, TLP, and AP) were identified based on their staining intensities, cell shapes and configurations of their cytoplasmic processes. Round or oval cells with short thick processes (SP) and cells with thick or thin long processes (TLP) were common in younger rats (1 day-1 week), while cells with attenuated processes (AP) preponderated in older animals (2-3 weeks). The immunoreactivity of microglial cells was gradually reduced as the cells differentiated progressively from the SP through the TLP type into the AP form. Similar results were obtained using the monoclonal antibody OX-18 and the isolectin Griffonia simplicifolia. None of the cells were stained with the antibody OX-6. A quantitative study showed a rapid increase in the cell density of OX-42 positive cells in both the gray and white matter from 1 day to 2 weeks of age, but this appeared to decrease thereafter. The increase in the cell density was attributed to the active proliferation of the cells as shown by the detection of many bromodeoxyuridine-labelled cells in the same region. Its reduction in 3-week-old rats was most probably due to the apparent expansion of the spinal cord as a result of the growth of its fibre size and other structural elements.

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Studies of activated microglia and macrophages in lumbosacral spinal cord following an intraperitoneal injection of 6-aminonicotinamide into adult rats.

The anterior horns of the lumbosacral segment of the spinal cord in rats showed an extensive lesion following an intraperitoneal administration of 6-amino-nicotinamide (6-AN). Neuronal chromatolysis was observed in some of the large efferent neurons 1-7 days after the injection of 6-AN. The capability in their uptake of fluorogold and its retrograde transport was comparable to those in the normal rats. Small neurons presumably internuncial cells underwent degeneration. 8 weeks after 6-AN injection, all the surviving neurons appeared normal. 1 day after 6-AN injection microglial cells appeared activated as evidenced by the hypertrophy and expansion of their processes. A large number of macrophages were observed in the lesioned site 7 days after the administration of 6-AN. The activated microglia and macrophages showed intense immunoreactivity with the monoclonal antibody OX-42. The immunoreactivity declined with time so that by 4 weeks after the injection of 6-AN very weak immunoreactivity was seen on some very branched cells. A similar pattern of immunoreactivity was observed with the monoclonal antibodies OX-18 and OX-6. It was concluded from this study that neuronal chromatolysis and neuronal degeneration induced the expression of CR3 receptors (marked by OX-42) and MHC encoded antigens (marked by OX-18 and OX-6) in activated microglia and macrophages. With time the immunoreactivity decreased so that by 4 weeks after the administration of 6-AN only faint immunoreactivity was observed on some branched cells.(ABSTRACT TRUNCATED AT 250 WORDS)

6-Aminonicotinamide↗

Intraventricular macrophages in the lateral ventricles with special reference to epiplexus cells: a quantitative analysis and their uptake of fluorescent tracer injected intraperitoneally in rats of different ages.

The labelling of epiplexus cells associated with the choroid plexus in the lateral ventricles was examined in rats of different ages with the fluorescent dye, rhodamine isothiocyanate (RhIc). A quantitative study was also attempted; this showed that the number of epiplexus cells and their related cells, namely supraependymal and free-floating cells, increased with age. The mean absolute number of epiplexus cells ranged from approximately 700 in the newborn to approximately 2200 in rats of 17 d of age; thereafter it remained unchanged. The number of free-floating cells also increased substantially but showed considerable individual variation. Following i.p. injection, the tracer was rapidly taken up by the epiplexus cells. This provided strong support for their phagocytic nature. In the newborn (1 d) and developing (13 d, 17 d) rats, RhIc-labelled epiplexus cells were first observed 3 h after the injection. In adult rats, labelled cells were not observed until 12 h after injection. In either case, the fluorescence in the epiplexus cells gradually increased with time. It is suggested from this study that the blood-CSF barrier in the choroid plexus in postnatal rats is incomplete, thereby allowing a rapid transvascular diffusion of the injected RhIc into the blood circulation. The fluorescent dye which enters the ventricle by way of the choroid epithelium is subsequently taken up by the epiplexus cells. Such an unimpeded passage, however, is reduced in the adult rats, probably due to the maturation of the blood capillaries as well as the choroid epithelium.

Aging↗

Uptake of tracer by the epiplexus cells via the choroid plexus epithelium following an intravenous or intraperitoneal injection of horseradish peroxidase in rats.

Rapid passage of horseradish peroxidase (HRP) from the blood circulation to the cerebrospinal fluid was demonstrated in postnatal rats. At 30 min-1 h after an intravenous (i.v.) injection of HRP, the extravasated tracer from the blood vessels entered the connective tissue of the choroid plexus to reach the epithelial intercellular spaces where it was retarded by the apical tight junctions. The HRP which accumulated in widened intercellular spaces was readily endocytosed by the epithelial cells, notably at their lateral surfaces. This was especially pronounced 3 h after the injection. The endocytosed HRP was either routed to lysosomes or discharged apically by exocytosis into the CSF via membrane-bound vesicles by the epithelial cells. After longer survival periods, i.e. 6 h after injection, the intercellular spaces were relatively clear of tracer. HRP-labelled vacuoles or vesicles had diminished with a concomitant increase in the number of lysosomes containing HRP reaction product. In the course of HRP injection, the epiplexus cells residing on the choroid epithelium progressively accumulated HRP by endocytosis so that in rats killed 6 h after injection, the cells were heavily loaded with HRP incorporated into massive lysosomes. The labelling pattern of epithelial and epiplexus cells in rats injected intraperitoneally followed that observed in those receiving i.v. injections. These results suggest that the epiplexus cells together with lysosomal activity by the choroid epithelial cells serve as a protective line of defence for the blood-CSF barrier which appears to be inefficient.

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