Imaging of non tumorous and tumorous human brain tissue with full-field optical coherence tomography

A prospective study was performed on neurosurgical samples from 18 patients to evaluate the use of Full-Field Optical Coherence Tomography (FF-OCT) in brain tumor diagnosis. FF-OCT captures en face slices of tissue samples at 1\mum resolution in 3D with a typical 200\mum imaging depth. A 1cm2 specimen is scanned at a single depth and processed in about 5 minutes. This rapid imaging process is non-invasive and 30 requires neither contrast agent injection nor tissue preparation, which makes it particularly well suited to medical imaging applications. Temporal chronic epileptic parenchyma and brain tumors such as meningiomas, low- grade and high-grade gliomas, and choroid plexus papilloma were imaged. A subpopulation of neurons, myelin fibers and CNS vasculature were clearly identified. Cortex could be discriminated from white matter, but individual glial cells as astrocytes (normal or reactive) or oligodendrocytes were not observable. This study reports for the first time on the feasibility of using FF-OCT in a real-time manner as a label-free non-invasive imaging technique in an intra-operative neurosurgical clinical setting to assess tumorous glial and epileptic margins

Understanding brain dysfunction in sepsis

Sepsis often is characterized by an acute brain dysfunction, which is associated with increased morbidity and mortality. Its pathophysiology is highly complex, resulting from both inflammatory and noninflammatory processes, which may induce significant alterations in vulnerable areas of the brain. Important mechanisms include excessive microglial activation, impaired cerebral perfusion, blood–brain-barrier dysfunction, and altered neurotransmission. Systemic insults, such as prolonged inflammation, severe hypoxemia, and persistent hyperglycemia also may contribute to aggravate sepsis-induced brain dysfunction or injury. The diagnosis of brain dysfunction in sepsis relies essentially on neurological examination and neurological tests, such as EEG and neuroimaging. A brain MRI should be considered in case of persistent brain dysfunction after control of sepsis and exclusion of major confounding factors. Recent MRI studies suggest that septic shock can be associated with acute cerebrovascular lesions and white matter abnormalities. Currently, the management of brain dysfunction mainly consists of control of sepsis and prevention of all aggravating factors, including metabolic disturbances, drug overdoses, anticholinergic medications, withdrawal syndromes, and Wernicke’s encephalopathy. Modulation of microglial activation, prevention of blood–brain-barrier alterations, and use of antioxidants represent relevant therapeutic targets that may impact significantly on neurologic outcomes. In the future, investigations in patients with sepsis should be undertaken to reduce the duration of brain dysfunction and to study the impact of this reduction on important health outcomes, including functional and cognitive status in survivors

Homeostatic and Tissue Reparation Defaults in Mice Carrying Selective Genetic Invalidation of CXCL12/Proteoglycan Interactions.

International audienceBACKGROUND: Interaction with heparan sulfate proteoglycans is supposed to provide chemokines with the capacity to immobilize on cell surface and extracellular matrix for accomplishing both tissue homing and signaling of attracted cells. However, the consequences of the exclusive invalidation of such interaction on the roles played by endogenous chemokines in vivo remain unascertained. METHODS AND RESULTS: We engineered a mouse carrying a Cxcl12 gene (Cxcl12(Gagtm)) mutation that precludes interactions with heparan sulfate structures while not affecting CXCR4-dependent cell signaling of CXCL12 isoforms (α, β, γ). Cxcl12(Gagtm/Gagtm) mice develop normally, express normal levels of total and isoform-specific Cxcl12 mRNA, and show increased counting of circulating CD34(+) hematopoietic precursor cells. After induced acute ischemia, a marked impaired capacity to support revascularization was observed in Cxcl12(Gagtm/Gagtm) animals associated with a reduced number of infiltrating cells in the ischemic tissue despite the massive expression of CXCL12 isoforms. Importantly, exogenous administration of CXCL12γ, which binds heparan sulfate with the highest affinity ever reported for a cytokine, fully restores vascular growth, whereas heparan sulfate-binding CXCL12γ mutants failed to promote revascularization in Cxcl12(Gagtm/Gagtm) animals. CONCLUSION: These findings prove the role played by heparan sulfate interactions in the functions of CXCL12 in both homeostasis and physiopathological settings and document for the first time the paradigm of chemokine immobilization in vivo

Type I IFN controls chikungunya virus via its action on nonhematopoietic cells

Chikungunya virus (CHIKV) is the causative agent of an outbreak that began in La Réunion in 2005 and remains a major public health concern in India, Southeast Asia, and southern Europe. CHIKV is transmitted to humans by mosquitoes and the associated disease is characterized by fever, myalgia, arthralgia, and rash. As viral load in infected patients declines before the appearance of neutralizing antibodies, we studied the role of type I interferon (IFN) in CHIKV pathogenesis. Based on human studies and mouse experimentation, we show that CHIKV does not directly stimulate type I IFN production in immune cells. Instead, infected nonhematopoietic cells sense viral RNA in a Cardif-dependent manner and participate in the control of infection through their production of type I IFNs. Although the Cardif signaling pathway contributes to the immune response, we also find evidence for a MyD88-dependent sensor that is critical for preventing viral dissemination. Moreover, we demonstrate that IFN-α/β receptor (IFNAR) expression is required in the periphery but not on immune cells, as IFNAR−/−→WT bone marrow chimeras are capable of clearing the infection, whereas WT→IFNAR−/− chimeras succumb. This study defines an essential role for type I IFN, produced via cooperation between multiple host sensors and acting directly on nonhematopoietic cells, in the control of CHIKV

Cryptococcal Cell Morphology Affects Host Cell Interactions and Pathogenicity

Cryptococcus neoformans is a common life-threatening human fungal pathogen. The size of cryptococcal cells is typically 5 to 10 µm. Cell enlargement was observed in vivo, producing cells up to 100 µm. These morphological changes in cell size affected pathogenicity via reducing phagocytosis by host mononuclear cells, increasing resistance to oxidative and nitrosative stress, and correlated with reduced penetration of the central nervous system. Cell enlargement was stimulated by coinfection with strains of opposite mating type, and ste3aΔ pheromone receptor mutant strains had reduced cell enlargement. Finally, analysis of DNA content in this novel cell type revealed that these enlarged cells were polyploid, uninucleate, and produced daughter cells in vivo. These results describe a novel mechanism by which C. neoformans evades host phagocytosis to allow survival of a subset of the population at early stages of infection. Thus, morphological changes play unique and specialized roles during infection

ETUDE DE L'APOPTOSE NEURONALE DANS LES MALADIES A PRIONS

PARIS12-CRETEIL BU Médecine (940282101) / SudocPARIS-BIUM (751062103) / SudocSudocFranceF

Les cellules souches musculaires dérivées de la moelle osseuse (mise en évidence et étude de l'impact thérapeutique)

Nous avons utilisé un modèle murin de reconstitution médullaire à l'aide de moelle osseuse de souris transgéniques exprimant la protéine GFP " green fluorescent protein ". La protéine fluorescente GFP sert de marqueur pour les cellules du donneur dans les tissus du receveur. Grâce à ce modèle, nous avons montré qu'il existe des cellules, provenant de la moelle osseuse, (i) en position interstitielle exprimant des marqueurs de cellules souches (ii) en position satellite exprimant des marqueurs canoniques de cellules satellites et capables de fusionner pour donner des fibres musculaires. Ces fibres GFP+ sont plus nombreuses, après la greffe, chez les souris mdx, déficientes en dystrophine. L'expression de la dystrophine, dans ces fibres GFP+, reste limitée au site de fusion alors que la GFP diffuse loin de celui Ces résultats suggèrent que les thérapies cellulaires pourraient, plus volontiers, être adaptées aux corrections de déficit en protéines solubles plutôt que membranaires.We used transplantation of green fluorescent bone marrow to irradiated mice. The green fluorescent protein serves as an unambiguous marker of donor cell in the recipient tissues. Using this procedure, we demonstrate bone marrow-derived cells (i) in interstitial location expressing stem cell markers (ii) in satellite cell niche expressing canonical markers of satellite cells and able to fuse to form muscle fibers. These GFP+ fibers are more numerous after bone-marrow transplantation, in mdx mice with dystrophin deficiency. Dystrophin expression, in GFP+ fibers, is restricted to the site of fusion whereas GFP diffuse far from it. These results suggest that cell therapy could be, in the future, more appropriate to correct soluble protein deficiency than membrane associated protein.PARIS12-CRETEIL BU Multidisc. (940282102) / SudocSudocFranceF

Peripheral primitive neuroectodermal tumor of the cauda equina in an elderly patient. Case report.

International audiencePrimitive neuroectodermal tumors (PNETs) are aggressive neoplasms composed predominantly of undifferentiated cells that show evidence of neural differentiation. Although their classification remains disputed, PNETs are recognized as primary tumors in both the central and peripheral nervous systems. These rare tumors usually occur in children or young adults and are typically metastatic to the spinal cord. The authors report the case of a 70-year-old man with no significant medical history, in whom a peripheral PNET was demonstrated that, based on clinical and imaging findings, manifested as a nonspecific intrathecal tumoral process arising from the cauda equina. Although this lesion is rare in the elderly, the authors' case illustrates the importance of making this diagnosis as early as possible so that a treatment plan may be devised. The use of chemotherapy in association with radiotherapy in relation to the resection of the tumor should be reconsidered

Normal muscle regeneration requires a tight control of muscle cell fusion by tetraspanins CD9 and CD81

International audienceSkeletal muscle regeneration after injury follows a remarkable sequence of synchronized events. However, the mechanisms regulating the typical organization of the regenerating muscle at different stages remain largely unknown. Here we show that muscle regeneration in mice lacking either CD9 or CD81 is abnormal and characterized by the formation of discrete giant dystrophic myofibres, which form more quickly in the absence of both tetraspanins. We also show that, in myoblasts, these two tetraspanins associate with the immunoglobulin domain molecule CD9P-1 (EWI-F/FPRP), and that grafting of CD9P-1-depleted myoblasts in regenerating muscles also leads to abnormal regeneration. In vitro myotubes lacking CD9P-1 or both CD9 and CD81 fuse with a higher frequency than normal myotubes. Our study unveils a mechanism preventing inappropriate fusion of myotubes that has an important role in the restitution of normal muscle architecture during muscle regeneration