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S Ghandour

Publications and source records attributed to S Ghandour.

11 recordsLinked to original sources
PubMed2001

Inflammatory response to cold injury in remote organs is reduced by corticotropin-releasing factor.

Current experimental evidence concerning the potential activity of corticotropin releasing factor (CRF) in inflammatory processes still remains controversial. To determine whether CRF has protective effects on three remote organs (liver, lung and stomach) affected by cold injury and to characterize the role of neutrophils in cold-induced inflammation, dorsums of anesthetized rats were exposed for 5 min to a 22% NaCl solution maintained at -20+/-0.5 degrees C and the rats were sacrificed at 24 h after the cold injury. The results indicate that cold-exposure-induced edema in the liver, lung and stomach was blocked by subcutaneous (s.c.; 1.2 and 12 nmol/kg; 30 min before cold trauma) CRF pretreatment, while the central administration of CRF (intracisternally (i.c.); 0.30 and 1.5 nmol/rat; 15 min before cold) had the similar effect at the higher dose. Histological assessment and the tissue myeloperoxidase activities also revealed that CRF given peripherally has a protective role in damage generation. Moreover, CRF had a facilitatory effect in the recovery of the body temperature following cold exposure. In conclusion, CRF is likely to act on its peripheral receptors in the inflamed remote organs, suppressing the edematogenic effects of inflammatory mediators, some of which are neutrophil-derived.

Animals↗
PubMed1999

Involvement of de novo ceramide biosynthesis in lymphotoxin-induced oligodendrocyte death.

Both experimental and clinical studies suggest that lymphotoxin (LT) plays an important role in multiple sclerosis (MS) by inducing oligodendrocyte (OL) depletion. However, the mechanism of LT cytotoxicity is unknown. Because of the role of ceramide as a cell death mediator for a large variety of cytotoxic molecules, we have investigated the possible role of this second messenger in LT-induced cytotoxicity on SV40 immortalized new-born mice OL. Human recombinant LT exposure (50 ng/ml) resulted in intracellular ceramide accumulation which peaked at 48 h (approximately 170% increase) and paralleled LT-induced cytotoxicity. Moreover, fumonisin B1, a potent and specific ceramide synthase inhibitor, not only inhibited ceramide accumulation but also protected OL from LT cytotoxicity. These results suggest that LT-induced ceramide synthase stimulation and subsequent increased intracellular ceramide concentration are implicated in oligodendrocyte death.

Animals↗
PubMed1999

Increased density of oligodendrocytes in childhood ataxia with diffuse central hypomyelination (CACH) syndrome: neuropathological and biochemical study of two cases.

We report neuropathological, biochemical and molecular studies on two patients with childhood ataxia with diffuse central nervous system hypomyelination (CACH) syndrome, a leukodystrophy recently defined according to clinical and radiological criteria. Both had severe cavitating orthochromatic leukodystrophy without atrophy, predominating in hemispheric white matter, whereas U-fibers, internal capsule, corpus callosum, anterior commissure and cerebellar white matter were relatively spared. The severity of white matter lesions contrasted with the rarity of myelin breakdown products and astroglial and microglial reactions. In the white matter, there was an increase in a homogeneous cell population with the morphological features of oligodendrocytes, in many instances presenting an abundant cytoplasm like myelination glia. These cells were negative for glial fibrillary acidic protein and antibodies PGM1 and MIB1. Some were positive for myelin basic protein, proteolipid protein (PLP), and myelin oligodendrocyte glycoprotein, but the majority were positive for human 2'-3' cyclic nucleotide 3' phosphodiesterase and all were positive for carbonic anhydrase II, confirming that they are oligodendrocytes. Myelin protein and lipid content were reduced. The PLP gene, analyzed in one case, was not mutated or duplicated. The increased number of oligodendrocytes without mitotic activity suggests an intrinsic oligodendroglial defect or an abnormal interaction with axons or other glial cells. This neuropathological study supports the notion that CACH syndrome constitutes a specific entity.

Ataxia↗
PubMed1998

A gliotoxic factor and multiple sclerosis.

The pathogenesis of multiple sclerosis (MS) is unknown. Searching for possible toxic factors, it was found that 3-day exposure to heat-treated cerebrospinal fluid (CSF) from MS patients caused apoptotic death of astrocytes and oligodendrocytes, but not fibroblasts, myoblasts, Schwann cells, endothelial cells and neurons, in vitro. CSFs from other inflammatory or non-inflammatory neurological diseases showed no toxicity. Exposure of these glial cells to partially purified MS CSF produced DNA fragmentation, apoptotic bodies, chromatin condensation, cell shrinkage, and changes in the levels of known cytokines. A cytotoxic factor, called gliotoxin, was characterized chromatographically as a stable 17-kDa glycoprotein. Since this protein is highly cytotoxic for astrocytes and oligodendrocytes, it may represent an initial pathogenic factor, leading to the neuropathological features of MS, such as blood-brain barrier involvement and demyelination.

Animals↗
PubMed1995

Notochord and floor plate stimulate oligodendrocyte differentiation in cultures of the chick dorsal neural tube.

The regionalization of oligodendrocyte potentialities and the cellular interactions leading to the expression of the oligodendrocyte phenotype have been analyzed in the embryonic chick spinal cord. Dorsal and ventral regions of the spinal cord of 4-day-old embryos (E4) were cultivated separately. Oligodendrocyte differentiation was monitored at various times after explantation, using specific oligodendrocyte markers. After 2 weeks, several hundreds of differentiated oligodendrocytes were invariably observed in ventral cultures whereas significant numbers of oligodendrocytes failed to develop in dorsal spinal cord cultures. However, the E7 dorsal spinal cord was found to produce large numbers of oligodendrocytes, indicating that the ventral restriction of oligodendrocyte potentialities is transient. To test whether ventrally derived signals might influence oligodendrocyte differentiation, E4 dorsal spinal cord microexplants were cocultivated with notochord segments or with floor plate tissue. Numerous oligodendrocytes were found in dorsal explants associated with either tissue, notochord or floor plate, but not in dorsal explants cultivated alone, indicating that cells competent to be induced along the oligodendrocyte phenotype exist in the dorsal spinal cord. These results show that oligodendrocyte differentiation potentialities are initially restricted to the ventral spinal cord and suggest that ventrally derived signals from notochord and floor plate influence oligodendrocyte differentiation in the embryonic spinal cord.

Animals↗
PubMed1992

Xenogenic transplantation into newborn rodent brain: neovascularization of the graft by the host.

Neoangiogenesis of transplants implanted into the brains of newborn rodent hosts was evaluated by immunohistochemistry for 2 weeks after the operation. The use of species-specific antibodies directed against mouse endothelial cells demonstrated the respective participation of the host and the donor in the formation of new vessels in the graft after crossed rabbit into mouse and mouse into rat transplantation experiments. We show that blood vessels made by host endothelial cells begin to penetrate the transplant 24 h after grafting, and cross it completely by 72 h. Simultaneously, host astrocytes invade the transplant.

Animals↗
PubMed1989

Mosaic reconstruction of blood vessels in mouse neocortical tissue transplanted into the third ventricle of rat brain.

Newborn mouse neocortical tissue was transplanted into the third ventricle of rat brain and the reconstruction and the origin of the blood vessels were investigated by using a monoclonal antibody against mouse endothelial surface antigen-1 (MESA-1). It was clearly demonstrated that some of the blood vessels in the graft originated in the donor mouse neocortical tissue. An India ink perfusion experiment revealed that the blood was supplied to the MESA-1-positive blood vessels. Furthermore, electron microscopic immunohistochemical studies demonstrated the existence of a mosaic reconstruction of blood vessels which consisted of mouse- and rat-derived vascular endothelial cells. It was concluded that the blood vessels originating in the donor tissue and those originating in the host tissue inoculate with each other in the grafted tissue.

Animals↗
PubMed1989

The cholinergic system in developing cerebellum: comparative study of normal, hypothyroid and underfed rats.

To overcome the deficiencies of previous findings, the activities of choline acetyltransferase (ChAT) and acetylcholinesterase (AchE) were studied at very short age intervals to allow a more precise definition of the shape and timing of their developmental curves in normal, hypothyroid and underfed rats. In addition, AchE expression in developing cerebellum was studied histochemically in these three neurological models. When compared with structural findings in the literature, the results provide the following information on the normal and abnormal developing cholinergic system, related or not to cerebellar neurotransmission (1) AchE activity, unlike ChAT, can be considered as a good marker of the developing cholinergic archicerebellum. (2) ChAT and AchE are transiently expressed together in functionally noncholinergic Purkinje cells. In contrast with most regions of the central nervous system, the high ratio of ChAT to AchE activities in the early stage of cerebellar development suggests an enhanced synthesis of acetylcholine (Ach). The level of ChAT activity correlates with Purkinje cell size, supporting the concept of a neurotrophic role of Ach in early maturing macroneurons. (3) The archicerebellar cholinergic network appears to be relatively well preserved from undernutrition and, to an even greater extent, from hypothyroidism, compared to other systems of neurotransmission formed later and more widely distributed throughout the cerebellum. The presynaptic compartment seems to be more affected than the postsynaptic compartment. (4) In disagreement with some data in the literature, the abnormalities induced by both abnormal thyroidal and nutritional states were found to be irreversible.

Acetylcholinesterase↗
PubMed1988

Influence of basic fibroblast growth factor on carbonic anhydrase expression by rat glial cells in primary culture.

Modifications of the morphology, the proliferation and the synthesis of carbonic anhydrase of glial cells in primary cultures maintained in defined medium have been investigated under the action of basic fibroblast growth factor. Cultures contained essentially three cell types: astrocytes which expressed glial fibrillary acidic protein, oligodendrocytes which were characterized by the presence of carbonic anhydrase and precursor cells in which these two proteins were detected by immunocytochemistry. In the presence of basic fibroblast growth factor astrocytes and oligodendrocytes underwent morphological changes, characterized by a fibrous aspect; astroglial cells acquired essentially several long processes and oligodendroglial cells formed generally two long processes. The factor increased the proliferation of these two cell types. The quantity of carbonic anhydrase per oligodendrocyte was enhanced in treated cultures. The double-stained precursor cells were present between days 7 and 11 of culture in defined medium, while in the presence of fibroblast growth factor these cells were more numerous and were still present after 14 days. The basic fibroblast growth factor stimulated the proliferation of these young glial cells and modified their morphology. But the differentiation of precursor cells towards one glial cell type appeared to be delayed.

Animals↗
PubMed1982

A surface marker for murine vascular endothelial cells defined by monoclonal antibody.

Spleen cells from a rat immunized with mouse cerebellar cells were fused with mouse myeloma cells. One of the hybridomas secreted a monoclonal antibody that reacts with a surface antigen on vascular endothelial cells. The antibody stained endothelial cells lining blood vessels in brain, heart, lung, kidney, and liver. It did not, however, stain endothelial cells lining hepatic sinusoids. Parenchymal cells were always negative. So far, an antigen of similar tissue distribution has not been described in the mouse and we have called it mouse endothelial surface antigen-1 (MESA-1). The antibody could be used as a highly specific usefulness for identifying endothelium-derived cells in culture has been demonstrated on cultures of dissociated mouse cerebellum, where it stained a subclass of fibronectin-expressing cells.

Animals↗