Case of neuro‐Behçet's disease successfully maintained a remission using infliximab for 2 years

Behçet's disease is a systemic inflammatory disorder with chronic remissions and relapses. Involvement of the central nervous system, called neuro‐Behçet's disease (NBD), is a serious complication. Although corticosteroids and immunosuppressive agents are used, there is no definite standard of treatment with long term‐effects for NBD. Here, we report a female case with NBD successfully treated by infliximab and corticosteroids for 2 years. Our report suggests treatment with infliximab may be effective for long‐term remission of NBD.     

MRI at 7 tesla and above: Demonstrated and potential capabilities

With more than 40 installed MR systems worldwide operating at 7 Tesla or higher, ultra‐high‐field (UHF) imaging has been established as a platform for clinically oriented research in recent years. Along with technical developments that, in part, have also been successfully transferred to lower field strengths, MR imaging and spectroscopy at UHF have demonstrated capabilities and potentials for clinical diagnostics in a variety of studies. In terms of applications, this overview article focuses on already achieved advantages for in vivo imaging, i.e., in imaging the brain and joints of the musculoskeletal system, but also considers developments in body imaging, which is particularly challenging. Furthermore, new applications for clinical diagnostics such as X‐nuclei imaging and spectroscopy, which only really become feasible at ultra‐high magnetic fields, will be presented. J. Magn. Reson. Imaging 2015;41:13–33. © 2014 Wiley Periodicals, Inc .     

Neuroprotective effects of PDGF against oxidative stress and the signaling pathway involved

The neuroprotective effects of platelet‐derived growth factor (PDGF) and the major signaling pathways involved in these were examined using primary cultured mouse cortical neurons subjected to H₂O₂‐induced oxidative stress. The specific function of the PDGF β‐receptor (PDGFR‐β) was examined by the selective deletion of the corresponding gene using the Cre‐loxP system in vitro. In wild‐type neurons, PDGF‐BB enhanced the survival of these neurons and suppressed H₂O₂‐induced caspase‐3 activation. The prosurvival effect of PDGF‐AA was less than that of PDGF‐BB. PDGF‐BB highly activated Akt, extracellular signal‐regulated kinase (ERK), c‐jun amino‐terminal kinase (JNK) and p38. PDGF‐AA activated these molecules at lesser extent than PDGF‐BB. In particular, PDGF‐AA induced activation of Akt was at very low level. The neuroprotective effects of PDGF‐BB were antagonized by inhibitors of phosphatidylinositol 3‐kinase (PI3‐K), mitogen‐activated protein kinase kinase (MEK), JNK and p38. The PDGFR‐β‐depleted neurons showed increased vulnerability to oxidative stress, and less responsiveness to PDGF‐BB‐induced cytoprotection and signal activation, in which Akt activation was most strongly suppressed. After all, these results demonstrated the neuroprotective effects of PDGF and the signaling pathways involved against oxidative stress. The effects of PDGF‐BB were more potent than those of PDGF‐AA. This might be due to the activation and additive effects of two PDGFRs after PDGF‐BB stimulation. Furthermore, the PI3‐K/Akt pathway that was deduced to be preferentially activated by PDGFR‐β may explain the potent effects of PDGF‐BB. © 2009 Wiley‐Liss, Inc.     

Age-related decreases in NAD(P)H and glutathione cause redox declines before ATP loss during glutamate treatment of hippocampal neurons

Age-related glutamate excitotoxicity depends in an unknown manner on active mitochondria, which are key determinants of the cellular redox potential. Compared with embryonic and middle-aged neurons, old-aged rat hippocampal neurons have a lower resting reduced nicotinamide adenine dinucleotide (phosphate) (NAD(P)H) and a lower redox ratio (NAD(P)H/flavin adenine nucleotide). Glutamate treatment resulted in an initial increase in NAD(P)H concentrations in all ages, followed by a profound calcium-dependent, age-related decline in NAD(P)H concentration and redox ratio. With complex I of the electron transport chain inhibited by rotenone, treatment with glutamate or ionomycin only resulted in the increase in NAD(P)H fluorescence. High-performance liquid chromatography analysis of adenine nucleotides in brain extracts showed 50% less nicotinamide adenine dinucleotide (NADH) and almost twice as much oxidized nicotinamide adenine dinucleotide, demonstrating a more oxidized ratio in old than middle-aged brain. Resting glutathione content also declined with age and further decreased with glutamate treatment without accompanying changes in adenosine triphosphate levels. We conclude that age does not affect production of NADH by dehydrogenases but that old-aged neurons consume more NADH and glutathione, leading to a catastrophic decline in redox ratio.     

F3/contactin-related proteins in Helix pomatia nervous tissue (HCRPs): distribution and function in neurite growth and neurotransmitter release

By using antibodies against mouse F3/contactin, we found immunologically related glycoproteins expressed in the nervous tissue of the snail Helix pomatia. Helix contactin-related proteins (HCRPs) include different molecules ranging in size from 90 to 240 kD. Clones isolated from a cDNA expression library allowed us to demonstrate that these proteins are translated from a unique 6.3-kb mRNA, suggesting that their heterogeneity depends on posttranslational processing. This is supported by the results of endoglycosidase F treatment, which indicate that the high-molecular-weight components are glycosylation variants of the 90-kD chain. In vivo and in cultures, HCRPs antibodies label neuronal soma and neurite extensions, giving the appearance of both cytoplasmic and cell surface immunostaining. On the other hand, no expression is found on nonneural tissues. Functionally, HCRPs are involved in neurite growth control and appear to modulate neurotransmitter release, as indicated by the inhibiting effects of specific antibodies on both functions. These data allow the definition of HCRPs glycoproteins as growth-promoting molecules, suggesting that they play a role in neurite development and presynaptic terminal maturation in the invertebrate nervous system.     

Negative modulation of presynaptic activity by zinc released from Schaffer collaterals

The role of zinc in excitation of Schaffer collateral-CA1 pyramidal cell synapses is poorly understood. Schaffer collaterals stained with ZnAF-2 or ZnAF-2DA, a membrane-impermeable or a membrane-permeable zinc indicator, respectively, were treated by tetanic stimulation (200 Hz, 1 sec). Extracellular and intracellular ZnAF-2 signals were increased in the stratum radiatum of the CA1, in which Schaffer collateral synapses exist. Both the increases were completely blocked in the presence of 1 mM CaEDAT, a membrane-impermeable zinc chelator, suggesting that 1 mM CaEDTA is effective for chelating zinc released from Schaffer collaterals. The role of Schaffer collateral zinc in presynaptic activity was examined by using FM4-64, a fluorescent indicator for vesicular exocytosis. The decrease in FM4-64 signal during tetanic stimulation (10 Hz, 180 sec) was enhanced in Schaffer collaterals in the presence of 1 mM CaEDTA but suppressed in the presence of 5 microM ZnC1(2), suggesting that zinc released from Schaffer collaterals suppresses presynaptic activity during tetanic stimulation. When Schaffer collateral synapses stained with calcium orange AM, a membrane-permeable calcium indicator, were regionally stimulated with 1 mM glutamate, calcium orange signal was increased in the CA1 pyramidal cell layer. This increase was enhanced in the presence of CaEDTA and attenuated in the presence of zinc. These results suggest that zinc attenuates excitation of Schaffer collateral synapses elicited with glutamate via suppression of presynaptic activity.