The expression of cyclooxygenase-2 (COX-2) and the synthesis of prostaglandin E2 (PGE 2 ) as well as of cytokines such as interleukin-6 (IL-6) have all been suggested to propagate neuropathology in different brain disorders such as HIV-dementia, prion diseases, stroke and Alzheimer's disease. In this report, we show that PGE 2 -stimulated IL-6 release in U373 MG human astroglioma cells and primary rat astrocytes. PGE 2 -induced intracellular cAMP formation was mediated via prostaglandin E receptor 2 (EP2), but inhibition of cAMP formation and protein kinase A or blockade of EP1/ EP2 receptors did not affect PGE 2 -induced IL-6 synthesis. This indicates that the cAMP pathway is not part of PGE 2 -induced signal transduction cascade leading to IL-6 release.The EP3/EP1-receptor agonist sulprostone failed to induce IL-6 release, suggesting an involvement of EP4-like receptors. PGE 2 -activated p38 mitogen-activated kinase (p38 MAPK) and protein kinase C (PKC). PGE 2 -induced IL-6 synthesis was inhibited by speci®c inhibitors of p38 MAPK (SB202190) and PKC (GF203190X). Although, up to now, EP receptors have only rarely been linked to p38 MAPK or PKC activation, these results suggest that PGE 2 induces IL-6 via an EP4-like receptor by the activation of PKC and p38 MAPK via an EP4-like receptor independently of cAMP.
To estimate the frequency of persistent Borna disease virus (BDV) infections of the human central nervous system and to determine which neuropsychiatric disorders might be associated with this viral infection, reverse transcription-nested polymerase chain reaction was used to screen a large collection of autopsy brain samples for the presence of BDV-specific nucleic acids. The presence of BDV RNA was found in 3 brains of persons with psychiatric symptoms and prominent hippocampal degeneration previously reported to be positive by others. However, no BDV RNA was detected in 86 randomly collected brains from persons with various psychiatric disorders, including schizophrenia, affective disorders, and Alzheimer's disease, or from suicide victims or in 52 brains from healthy controls. Furthermore, no BDV-RNA was detected in 16 surgical brain samples from persons with epilepsy-associated hippocampal sclerosis. These results indicate that life-long persistent BDV infections are rare in humans and that such infections may be associated with certain forms of hippocampal degeneration.
Serial samples, spanning an observation period of 4 to 10 years, from five patients with anti-Hu associated paraneoplastic neurological syndromes (PNS) were investigated with an enzyme linked immunosorbent assay (ELISA) employing recombinant HuD protein as antigen. In one patient the anti-Hu antibody concentration converted from negative to highly positive levels after the onset of neurological symptoms. These findings argue in favour of the idea that an autoimmune process, which is generated at the beginning of the neurological disease, causes the anti-Hu associated PNS. Serum samples obtained shortly after the beginning of the PNS were available from two other patients. The anti-Hu antibody levels in these latter patients increased from modest to highly positive anti-Hu antibody in follow up samples. In two patients a clear decrease of the anti-HuD antibody concentration together with an improvement of paraneoplastic neurological symptoms after successful tumour treatment were seen. Overall these data suggest that there might be a correlation between the anti-HuD antibody level and the clinical course of paraneoplastic neurological symptoms which supports further the hypothesis that an autoimmune process is responsible for the anti-Hu associated paraneoplastic neurological symptoms.
Clinical and laboratory data from a patient with Guillain-Barré syndrome indicated a probable etiological correlation of polyradiculitis to the intravenous administration of streptokinase. Oligoclonal IgG bands in the cerebrospinal fluid and serum were shown to be specific for streptokinase. Serum titers of streptokinase were elevated 64-fold for IgG, 16-fold for IgM, and 4-fold for IgA compared to controls. Clinical symptoms of Guillain-Barré syndrome are thought to result from streptokinase antibody complex mediated damage to the local blood-nerve barrier. The pathogenic relevance of autoantibodies to albumin and proteins of the central and peripheral nervous systems, occurring early after onset of symptoms, remains to be determined.
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