Movement disorders in encephalitis induced by Rhodococcus aurantiacus infection relieved by the administration of L-dopa and anti-T-cell antibodies.
(9/1379)
Mice injected with Rhodococcus aurantiacus by the intravenous (i.v.) route show neurological disorders, hemiparesis, vertical headshake and turn-round gait after day 7 postinfection (p.i.). Neurological symptoms caused by i.v. inoculation of R. aurantiacus were relieved by treatment with levodopa (l-dopa). R. aurantiacus was isolated from the brain and was found to be completely eliminated at day 7 p. i. Focal encephalitis was mainly observed in the brain stem, and T cells could be isolated from the brain after day 7 p.i. Administration of both an anti-CD4 monoclonal antibody (mAb) and an anti-CD8 mAb suppressed neurological symptoms. These results suggest that R. aurantiacus induces movement disorders in mice, and that the symptoms are mediated by T cells infiltrating the brain, rather than directly by the bacterium. (+info)
Interferon-gamma receptor-mediated but not tumor necrosis factor receptor type 1- or type 2-mediated signaling is crucial for the activation of cerebral blood vessel endothelial cells and microglia in murine Toxoplasma encephalitis.
(10/1379)
The regulatory role of interferon-gamma receptor (IFN-gammaR)- and tumor necrosis factor receptor (TNFR)-mediated immune reactions for the activation of cerebral endothelial cells, microglia, and astrocytes was evaluated in a model of murine Toxoplasma encephalitis (TE). Brain endothelial cells of wild-type mice reacted in response to Toxoplasma infection with a strong up-regulation of the vascular cell adhesion molecule, the intercellular adhesion molecule (ICAM)-1, and major histocompatibility complex (MHC) class I and II antigens. A similar response was seen in mice genetically deficient for either TNFR1, TNFR2, or both TNFRs, whereas IFN-gammaR-deficient (IFN-gammaR0/0) mice were found to be defective in the up-regulation of these molecules. However, recruitment of leukocytes to the brain and their intracerebral movement were not impaired in IFN-gammaR0/0 mice. In addition, microglia of Toxoplasma gondii-infected IFN-gammaR0/0 mice failed to induce expression of ICAM-1, leukocyte function-associated antigen (LFA)-1, and MHC class I and II antigens, whereas wild-type and TNFR-deficient mice up-regulated these molecules. Moreover, TNF-alpha mRNA production of F4/80(+) microglia/macrophages was impaired in IFN-gammaR0/0 mice, but not in TNFR-deficient mutants. However, induction of interleukin (IL)-1beta, IL-10, IL-12p40, and IL-15 mRNA was independent of IFN-gammaR and TNFR signaling. In conclusion, IFN-gammaR, but not TNFR signaling, is the major pathway for the activation of endothelial cells and microglia in murine TE. These findings differ from observations in other inflammatory central nervous system disorders, indicating specific regulatory mechanisms in this parasitic cerebral infection. (+info)
A serologic marker of paraneoplastic limbic and brain-stem encephalitis in patients with testicular cancer.
(11/1379)
BACKGROUND: In patients with cancer, symptoms of limbic and brain-stem dysfunction may result from a paraneoplastic disorder. Paraneoplastic limbic or brain-stem encephalitis occurs more frequently with testicular cancer than with most other cancers. We sought antineuronal antibodies that might be used in a diagnostic test for this syndrome. METHODS: Immunohistochemical and immunoblotting techniques were used to detect serum and cerebrospinal fluid antibodies. Serologic screening of a complementary DNA library and Northern blotting were used to clone the target antigen and determine which tissues expressed it. RESULTS: Of 13 patients with testicular cancer and paraneoplastic limbic or brain-stem encephalitis (or both), 10 had antibodies in serum and cerebrospinal fluid against a 40-kd neuronal protein. These antibodies were used to clone a gene that we call Ma2, which codes for a protein (Ma2) that was recognized by serum from the 10 patients, but not by serum from 344 control subjects. Ma2 was selectively expressed by normal brain tissue and by the testicular tumors of the patients. Ma2 shares homology with Ma1, a "brain-testis-cancer" gene related to other paraneoplastic syndromes and tumors. CONCLUSIONS: The serum of patients with subacute limbic and brain-stem dysfunction and testicular cancer contains antibodies against a protein found in normal brain and in testicular tumors. Detection of these antibodies supports the paraneoplastic origin of the neurologic disorder and could be of diagnostic importance. (+info)
Evidence that Par-4 participates in the pathogenesis of HIV encephalitis.
(12/1379)
Progressive neuronal degeneration in brain regions involved in learning and memory processes is a common occurrence in patients infected with human immunodeficiency virus type 1 (HIV-1). We now report that levels of Par-4, a protein recently linked to neuronal apoptosis in Alzheimer's disease, are increased in neurons in hippocampus of human patients with HIV encephalitis and in monkeys infected with a chimeric strain of HIV-1 and simian immunodeficiency virus. Par-4 levels increased rapidly in cultured hippocampal neurons following exposure to the neurotoxic HIV-1 protein Tat, and treatment of the cultures with a Par-4 antisense oligonucleotide protected the neurons against Tat-induced apoptosis. Additional findings show that Par-4 participates at an early stage of Tat-induced neuronal apoptosis before caspase activation, oxidative stress, and mitochondrial dysfunction. Our data suggest that Par-4 may be a mediator of neuronal apoptosis in HIV encephalitis and that therapeutic approaches targeting the Par-4 apoptotic cascade may prove beneficial in preventing neuronal degeneration and associated dementia in patients infected with HIV-1. (+info)
Herpes simplex encephalitis after brain surgery: case report and review of the literature.
(13/1379)
Intracranial infection after neurosurgical intervention most often is caused by bacteria. A rare case of fatal herpes simplex encephalitis after removal of a meningioma is described and similar cases reported in the literature are reviewed. Recent diagnostic tools, including detection of herpes viral DNA sequences by polymerase chain reaction, complement clinical suspicion and facilitate mandatory early diagnosis, because herpes encephalitis, without rapid initiation of treatment, may lead to severe disability or death. (+info)
Imaging and laboratory investigation in herpes simplex encephalitis.
(14/1379)
A 14 day old baby presented with signs of an acute encephalitis. Clinically, herpes simplex encephalitis (HSE) was suspected. Early MRI and EEG were normal and there was rapid clinical improvement. A negative polymerase chain reaction (PCR) result on the initial CSF sample seemed to make HSE most unlikely. This diagnosis was subsequently proved after demonstration of specific antibody production using immunoelectrophoresis of the CSF. The child had extensive damage to brain tissue. The need for sequential analysis of CSF in making or refuting this diagnosis is illustrated. (+info)
Inflammatory responses and their impact on beta-galactosidase transgene expression following adenovirus vector delivery to the primate caudate nucleus.
(15/1379)
An E1, E3 deleted adenovirus vector, serotype 5, carrying the marker gene LacZ was bilaterally microinfused into the caudate nuclei of 10 St Kitts green monkeys. The location and number of cells expressing transgene and host immunologic response were evaluated at 1 week (n = 2) and 1 month (n = 8) following vector infusion. A large number of cells expressed beta-galactosidase in some monkeys, exceeding 600000 in one monkey, but no expression was seen in three of 10. All monkeys had positive adenoviral antibody titers before vector infusion, indicating the possibility of previous exposure to some adenovirus, but only one showed a significant increase in titer afterwards. Inflammatory cell markers revealed an inverse correlation between transgene expression and the extent of inflammatory response. Dexamethasone administered immediately before and for 8 days following vector delivery, however, had no effect on transgene expression. The demonstration of significant inflammatory responses in the brain of some individual primates, including demyelination, indicates the need for new generations of adenovirus vectors, or the successful suppression of inflammatory responses, before this vector is suitable for non-cytotoxic clinical applications in the CNS. (+info)
Inflammatory responses in the cerebral cortex after ischemia in the P7 neonatal Rat.
(16/1379)
BACKGROUND AND PURPOSE: The contribution of inflammatory response to the pathogenesis of ischemic lesions in the neonate is still uncertain. This study described the chronological sequence of inflammatory changes that follow cerebral ischemia with reperfusion in the neonatal P7 rat. METHODS: P7 rats underwent left middle cerebral artery electrocoagulation associated with 1-hour left common carotid artery occlusion. The spatiotemporal pattern of cellular responses was characterized immunocytochemically with the use of antibodies against rat endogenous immunoglobulins to visualize the area of the breakdown of the blood-brain barrier. Infiltration of neutrophils and T lymphocytes was demonstrated by antibodies against myeloperoxidase and a pan-T cell marker, respectively. Antibodies ED1 and OX-42 were applied to identify microglial cells and macrophages. The response of astrocytes was shown with antibodies against glial fibrillary acidic protein. Cell survival was assessed by Bcl-2 expression. Cell death was demonstrated by DNA fragmentation with the use of the terminal deoxynucleotidyl transferase-mediated dUTP biotin nick end labeling (TUNEL) assay and Bax immunodetection. RESULTS: Endogenous immunoglobulin extravasation through the blood-brain barrier occurred at 2 hours of recirculation and persisted until 1 month after ischemia. Neutrophil infiltration began at 24 hours and peaked at 72 to 96 hours (30+/-3.4 neutrophils per 0.3 mm(2); P<0.0001), then disappeared at 14 days after ischemia. T cells were observed between 24 and 96 hours of reperfusion. Resident microglia-macrophages exhibited morphological remnants and expressed the cell death inhibitor Bcl-2 at 24 hours of recirculation. They became numerous within the next 48 hours and peaked at 7 days after ischemia. Phenotypic changes of resident astrocytes were apparent at 24 hours, and they proliferated between 48 hours and 7 days after ischemia. Progressively inflammatory cells showed DNA fragmentation and the cell death activator Bax expression. Cell elimination continued until there was a complete disappearance of the frontoparietal cortex. CONCLUSIONS: These data demonstrate that perinatal ischemia with reperfusion triggers acute inflammatory responses with granulocytic cell infiltration, which may be involved in accelerating the destructive processes. (+info)