Experimental pneumococcal meningitis in mice: a model of intranasal infection.
(33/402)
Effective laboratory animal models of bacterial meningitis are needed to unravel the pathophysiology of this disease. Previous models have failed to simulate human meningitis by using a directly intracerebral route of infection. Hyaluronidase is a virulence factor of Streptococcus pneumoniae. In this study, a novel model of murine meningitis is described. Intranasal administration of S. pneumoniae with hyaluronidase induced meningitis in 50% of inoculated mice, as defined by a positive cerebrospinal fluid (CSF) culture and an inflammatory infiltrate in the meninges. None of the mice inoculated without hyaluronidase developed meningitis. Hyaluronidase was found to facilitate pneumococcal invasion of the bloodstream after colonization of the upper respiratory tract. Meningitis was characterized by pleocytosis of CSF and the induction of proinflammatory cytokines and CXC chemokines in brain tissue. These results indicate that this murine model mimics important features of human disease and allow for the use of this model for studying issues related to the pathophysiology and the treatment of pneumococcal meningitis. (+info)
Prevalence of psammoma bodies in meninges and choroid plexuses of raccoons (Procyon lotor) from Parramore Island, Virginia.
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Microscopic evidence of multifocal mineralizations (psammoma bodies) were seen in brains of 33/53 (62%) raccoons (Procyon lotor) necropsied on Parramore Island, Virginia. Most mineralized foci had concentric laminations and were present in small capillaries of meninges of the brain (15/33), in choroid plexus (3/33), or at both these sites (13/33). In 2 raccoons, the lesions were confined to the meninges of the proximal cervical spinal cord. In most cases, the affected vessels appeared to have been completely occluded. However, no evidence of ischemic changes in the brain parenchyma was seen, and none of the raccoons had abnormal neurologic signs prior to euthanasia. The condition appears to be a common incidental histopathologic finding in raccoons from the eastern United States. Although the exact cause of this condition is not known, a primary vascular insult with resultant dystrophic mineralization of the affected vessels is suspected. (+info)
Differential gene expression during meningeal-meningococcal interaction: evidence for self-defense and early release of cytokines and chemokines.
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Using microarray technology, we studied the early differential expression of 3,528 genes in human meningothelial cells in response to meningococcal challenge. Thirty-two genes were up-regulated, and four were down-regulated. Those up-regulated included the tumor necrosis factor alpha, interleukin-6 (IL-6), and IL-8 (but not IL-1beta) genes, suggesting that meningeal cells may be a local and early source of these cytokines. Also, a trend in up-regulation of anti-apoptotic genes and down-regulation of pro-apoptotic genes was observed. This is the first evidence that meningothelial cells may mount cytoprotective responses to pathogenic bacteria. (+info)
Neurotrophic factors and receptors in the immature and adult spinal cord after mechanical injury or kainic acid.
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Delivery of neurotrophic factors to the injured spinal cord has been shown to stimulate neuronal survival and regeneration. This indicates that a lack of sufficient trophic support is one factor contributing to the absence of spontaneous regeneration in the mammalian spinal cord. Regulation of the expression of neurotrophic factors and receptors after spinal cord injury has not been studied in detail. We investigated levels of mRNA-encoding neurotrophins, glial cell line-derived neurotrophic factor (GDNF) family members and related receptors, ciliary neurotrophic factor (CNTF), and c-fos in normal and injured spinal cord. Injuries in adult rats included weight-drop, transection, and excitotoxic kainic acid delivery; in newborn rats, partial transection was performed. The regulation of expression patterns in the adult spinal cord was compared with that in the PNS and the neonate spinal cord. After mechanical injury of the adult rat spinal cord, upregulations of NGF and GDNF mRNA occurred in meningeal cells adjacent to the lesion. BDNF and p75 mRNA increased in neurons, GDNF mRNA increased in astrocytes close to the lesion, and GFRalpha-1 and truncated TrkB mRNA increased in astrocytes of degenerating white matter. The relatively limited upregulation of neurotrophic factors in the spinal cord contrasted with the response of affected nerve roots, in which marked increases of NGF and GDNF mRNA levels were observed in Schwann cells. The difference between the ability of the PNS and CNS to provide trophic support correlates with their different abilities to regenerate. Kainic acid delivery led to only weak upregulations of BDNF and CNTF mRNA. Compared with several brain regions, the overall response of the spinal cord tissue to kainic acid was weak. The relative sparseness of upregulations of endogenous neurotrophic factors after injury strengthens the hypothesis that lack of regeneration in the spinal cord is attributable at least partly to lack of trophic support. (+info)
Tumefactive fibroinflammatory lesion of the neck with progressive invasion of the meninges, skull base, orbit, and brain.
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SUMMARY: Tumefactive fibroinflammatory lesions of the head and neck are rare. CNS involvement has not been reported. We present a histologically proven case of a tumefactive fibroinflammatory lesion that originated in the left side of the neck and progressed over 2 years to involve the meninges, the cavernous sinuses, the right temporal lobe, and the right orbit. The lesion caused destruction of the skull base and a subdural hematoma. The relationship of the present lesion to idiopathic hypertrophic pachymeningitis and Tolosa-Hunt syndrome is discussed. (+info)
Endothelial cell laminin isoforms, laminins 8 and 10, play decisive roles in T cell recruitment across the blood-brain barrier in experimental autoimmune encephalomyelitis.
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An active involvement of blood-brain barrier endothelial cell basement membranes in development of inflammatory lesions in the central nervous system (CNS) has not been considered to date. Here we investigated the molecular composition and possible function of the extracellular matrix encountered by extravasating T lymphocytes during experimental autoimmune encephalomyelitis (EAE). Endothelial basement membranes contained laminin 8 (alpha4beta1gamma1) and/or 10 (alpha5beta1gamma1) and their expression was influenced by proinflammatory cytokines or angiostatic agents. T cells emigrating into the CNS during EAE encountered two biochemically distinct basement membranes, the endothelial (containing laminins 8 and 10) and the parenchymal (containing laminins 1 and 2) basement membranes. However, inflammatory cuffs occurred exclusively around endothelial basement membranes containing laminin 8, whereas in the presence of laminin 10 no infiltration was detectable. In vitro assays using encephalitogenic T cell lines revealed adhesion to laminins 8 and 10, whereas binding to laminins 1 and 2 could not be induced. Downregulation of integrin alpha6 on cerebral endothelium at sites of T cell infiltration, plus a high turnover of laminin 8 at these sites, suggested two possible roles for laminin 8 in the endothelial basement membrane: one at the level of the endothelial cells resulting in reduced adhesion and, thereby, increased penetrability of the monolayer; and secondly at the level of the T cells providing direct signals to the transmigrating cells. (+info)
Sacral meningeal cyst associated with valve-like mechanism--case report.
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A 58-year-old woman presented with low back pain radiating to the lower extremities. Magnetic resonance imaging revealed a cystic lesion in the sacrum compressing the nerve roots. At operation, a valve-like communication was found between the subarachnoid space and the cyst cavity in the vicinity of the sacral nerve root. The communication was obliterated with a purse-string suture and reinforced with a free muscle graft. Postoperatively, she reported improvement of the pain. Valve-like communication between the cyst cavity and subarachnoid space can cause enlargement of spinal meningeal cyst, and could also explain enlargement of sacral meningeal cyst. Surgical obliteration of the communication rather than the cyst resection is more important for sacral meningeal cyst. (+info)
Persistent reelin-expressing Cajal-Retzius cells in polymicrogyria.
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Cajal-Retzius (CR) cells are early-developing cells important in mammalian corticogenesis. Reelin, a protein secreted by CR cells, is essential for completion of neuronal migration and cortical lamination. Lack of reelin causes the 'reeler' phenotype in mice and autosomal recessive lissencephaly with cerebellar hypoplasia in man. Focal increases in reelin and CR cells are associated with thickening and local invaginations of the marginal zone and microgyria in animal studies. It has been suggested that abnormalities of reelin expression may be involved in human polymicrogyria. We have studied CR cells and reelin expression in pathological sections of human polymicrogyria to explore this possibility. Occurrence, distribution, morphology and reelin expression in CR cells were studied in 12 cases of human polymicrogyria, ranging from 21 gestational weeks to 10 years of age. Findings were compared with age-matched controls. Large, reelin-positive CR-like cells were more numerous in the majority of the polymicrogyria cases and persisted for longer than usual, up to 10 years of age. The CR-like cells tended to cluster and were most frequent in fused molecular layers in the polymicrogyria. Reelin-expressing CR-like cells were also found in bridges between the molecular layer and overlying leptomeningeal heterotopia and within the heterotopia itself. Clusters of CR-like cells were also found in adjacent non-polymicrogyric cortex. No clusters were seen in the control subjects. Increased numbers of CR-like cells were seen in both familial and acquired cases. In contrast to previous reports, the findings show that large CR-like cells persisted for longer than usual, up to 10 years of age, and that they may continue to express reelin. Their maximal aggregation in regions of polymicrogyria and overlying leptomeningeal heterotopia suggest an association between the presence of these cells and polymicrogyria, which we interpret in the light of recent findings concerning the roles of reelin and its downstream signalling pathway in neuronal and glial developmental dynamics and post-developmental function. (+info)