Diazoxide enhances excitotoxicity-induced neurogenesis and attenuates neurodegeneration in the rat non-neurogenic hippocampus.

Diazoxide, a well-known mitochondrial KATP channel opener with neuroprotective effects, has been proposed for the effective and safe treatment of neuroinflammation. To test whether diazoxide affects the neurogenesis associated with excitotoxicity in brain injury, we induced lesions by injecting excitotoxic N-methyl-d-aspartate (NMDA) into the rat hippocampus and analyzed the effects of a daily oral administration of diazoxide on the induced lesion. Specific glial and neuronal staining showed that NMDA elicited a strong glial reaction associated with progressive neuronal loss in the whole hippocampal formation. Doublecortin immunohistochemistry and bromo-deoxyuridine (BrdU)-NeuN double immunohistochemistry revealed that NMDA also induced cell proliferation and neurogenesis in the lesioned non-neurogenic hippocampus. Furthermore, glial fibrillary acidic protein (GFAP)-positive cells in the injured hippocampus expressed transcription factor Sp8 indicating that the excitotoxic lesion elicited the migration of progenitors from the subventricular zone and/or the reprograming of reactive astrocytes. Diazoxide treatment attenuated the NMDA-induced hippocampal injury in rats, as demonstrated by decreases in the size of the lesion, neuronal loss and microglial reaction. Diazoxide also increased the number of BrdU/NeuN double-stained cells and elevated the number of Sp8-positive cells in the lesioned hippocampus. These results indicate a role for KATP channel activation in regulating excitotoxicity-induced neurogenesis in brain injury.

Glucose pathways adaptation supports acquisition of activated microglia phenotype.

With its capacity to survey the environment and phagocyte debris, microglia assume a diversity of phenotypes to respond specifically through neurotrophic and toxic effects. Although these roles are well accepted, the underlying energetic mechanisms associated with microglial activation remain largely unclear. This study investigates microglia metabolic adaptation to ATP, NADPH, H(+) , and reactive oxygen species production. To this end, in vitro studies were performed with BV-2 cells before and after activation with lipopolysaccharide + interferon-γ. Nitric oxide (NO) was measured as a marker of cell activation. Our results show that microglial activation triggers a metabolic reprogramming based on an increased glucose uptake and a strengthening of anaerobic glycolysis, as well as of the pentose pathway oxidative branch, while retaining the mitochondrial activity. Based on this energy commitment, microglial defense capacity increases rapidly as well as ribose-5-phosphate and nucleic acid formation for gene transcription, essential to ensure the newly acquired functions demanded by central nervous system signaling. We also review the role of NO in this microglial energy commitment that positions cytotoxic microglia within the energetics of the astrocyte-neuron lactate shuttle.

ATP-dependent potassium channel blockade strengthens microglial neuroprotection after hypoxia-ischemia in rats.

Stroke causes CNS injury associated with strong fast microglial activation as part of the inflammatory response. In rat models of stroke, sulphonylurea receptor blockade with glibenclamide reduced cerebral edema and infarct volume. We postulated that glibenclamide administered during the early stages of stroke might foster neuroprotective microglial activity through ATP-sensitive potassium (K(ATP)) channel blockade. We found in vitro that BV2 cell line showed upregulated expression of K(ATP) channel subunits in response to pro-inflammatory signals and that glibenclamide increases the reactive morphology of microglia, phagocytic capacity and TNFα release. Moreover, glibenclamide administered to rats 6, 12 and 24h after transient Middle Cerebral Artery occlusion improved neurological outcome and preserved neurons in the lesioned core three days after reperfusion. Immunohistochemistry with specific markers to neuron, astroglia, microglia and lymphocytes showed that resident amoeboid microglia are the main cell population in that necrotic zone. These reactive microglial cells express SUR1, SUR2B and Kir6.2 proteins that assemble in functional K(ATP) channels. These findings provide that evidence for the key role of K(ATP) channels in the control of microglial reactivity are consistent with a microglial effect of glibenclamide into the ischemic brain and suggest a neuroprotective role of microglia in the early stages of stroke.

[Candidemia in AIDS. A retrospective study of nine cases]. / La candidemia en el síndrome de inmunodeficiencia adquirida. Estudio retrospectivo de nueve casos.

Prevalence of candidemia has increased during the last decade, numerous predisposing factors are invoked, like parenteral drug abuse in the case of brown heroin syndrome, neutropenia, prolonged antibiotic therapeutics and immunosupression. Only a few articles are published about candidemia. Candidemia in AIDS patients seems very low; its incidence is estimated approximately one candidemia per 120 patients.

[Syphilitic arthro-osteitis]. / Artroosteítis luética.

We report a black female with past history of sexual promiscuity who developed arthroosteitis of clavicula and sternoclavicular joint and cranial osteitis during secondary syphilis. Spirochaeta were identified in the material from osteoarticular biopsy. The patient was treated with benzathine penicillin, 2,400,000 U weekly for three weeks. There was a complete clinical recovery. We emphasize the uncommon occurrence of osteoarticular involvement in secondary syphilis and the exceptional character, according to the literature, of the finding of spirochaeta in the biopsy material. We discuss the differential diagnosis and we review the literature on secondary syphilis. We suggest that syphilis should be considered in the differential diagnosis of any acute arthritis or osteitis, particularly when the involved joint is the sternoclavicular and the patient is sexually promiscuous.