Gap 27

Enhanced gap junctional communication (GJC) between neurons is considered a major factor underlying the neuronal synchrony driving seizure activity. In addition, the hippocampal sharp wave ripple complexes, associated with learning and seizures, are diminished by GJC blocking agents. Although gap junctional blocking drugs inhibit experimental seizures, they all have other non-specific actions. Besides interneuronal GJC between dendrites, inter-axonal and inter-glial GJC is also considered important for seizure generation. Interestingly, in most studies of cerebral tissue from animal seizure models and from human patients with epilepsy, there is up-regulation of glial, but not neuronal gap junctional mRNA and protein. Significant changes in the expression and post-translational modification of the astrocytic connexin Cx43, and Panx1 were observed in an in vitro Co(++) seizure model, further supporting a role for glia in seizure-genesis, although the reasons for this remain unclear. Further suggesting an involvement of astrocytic GJC in epilepsy, is the fact that the expression of astrocytic Cx mRNAs (Cxs 30 and 43) is several fold higher than that of neuronal Cx mRNAs (Cxs 36 and 45), and the number of glial cells outnumber neuronal cells in mammalian hippocampal and cortical tissue. Pannexin expression is also increased in both animal and human epileptic tissues. Specific Cx43 mimetic peptides, Gap 27 and SLS, inhibit the docking of astrocytic connexin Cx43 proteins from forming intercellular gap junctions (GJs), diminishing spontaneous seizures. Besides GJs, Cx membrane hemichannels in glia and Panx membrane channels in neurons and glia are also inhibited by traditional gap junctional pharmacological blockers. Although there is no doubt that connexin-based GJs and hemichannels, and pannexin-based membrane channels are related to epilepsy, the specific details of how they are involved and how we can modulate their function for therapeutic purposes remain to be elucidated.

Background: Optic perineuritis (OPN) is a special optic neuropathy that has a distinct etiology from neuromyelitis optica spectrum disorders (NMOSDs) or multiple sclerosis (MS)-related optic neuritis (ON). The mechanisms of how this inflammation developed and invaded the nerve sheath remain unknown. This study is aimed to analyze the etiology and different clinical characteristics of OPN in a Chinese patient population. Methods: Neuro-ophthalmological examination, orbit magnetic resonance imaging (MRI) and a series of blood samples were used in this retrospective observational cohort study to compare characteristics of OPN with idiopathic demyelination optic neuritis (IDON). Results: Forty-four OPN cases (74 eyes) and 61 IDON cases (78 eyes) were analyzed. OPN cases included 33 cases (59 eyes) were associated with specific autoimmune diseases, 10 cases (13 eyes) were associated with infection diseases, 1 case was idiopathic disease. The causes of OPN with CTD were Graves' disease, Immunoglobulin G4-related disease (IgG-4 RD), granulomatosis with polyangiitis (GAP), systemic lupus erythematosus (SLE), Sarcoidosis, Rheumatoid arthritis, scleroderma, Behcet's disease, and gout. All patients received orbital MRI. Overall, 33 cases showed orbit fat infiltration. Specifically, nine cases with IgG-4 RD showed trigeminal nerve branch involvement, 12 cases with Graves' disease showed extraocular muscle belly enlargement, and 4 cases with GAP showed pterygopalatine fossa pseudotumor. Compared to IDON patients, OPN patients were older (p = 0.004) and more likely bilateral involvement 26 (78.79%) patients had bilateral involvement in OPN group vs. 17 (27.87%) in the IDON group (p < 0.001). Visual acuity scores using LogMAR testing was better in OPN patients compared to those with IDON, 0.55 ± 0.91 vs. 1.19 ± 1.24 (p < 0.001). Other ophthalmologic findings unique to the OPN group include 11 (33.33%) cases of ptosis, nine (27.27%) cases of diplopia, and 10 (30.30%) cases of exophthalmos, compared to zero cases of these conditions in the IDON group. Eight (13.11%) IDON patients also had multiple sclerosis (MS) and 7 (11.48%) patients had neuromyelitis which was significantly more than the zero patients in OPN group (p = 0.04). Conclusions: OPN had distinct etiologies and clinical characteristics from IDON and is more often associated with autoimmune diseases. Using OPN characteristics to diagnose autoimmune diseases should prove useful for clinicians when presented with patients that have multiorgan dysfunction that include ophthalmologic findings.

We examine the gender wealth gap with a focus on pension wealth and statutory pension rights. By taking into account employment characteristics of women and men, we are able to identify the extent to which the redistributive effect of pension rights reduces the gender wealth gap. The data for our analysis come from the German Socio-Economic Panel (SOEP), one of the few surveys that collects information on wealth and pension entitlements at the individual level. Pension wealth data are available in the SOEP for 2012 only. While the relative raw gender wealth gap is about 35% (or 31,000 euros) when analysing the standard measure of net worth, it shrinks to 28% when pension wealth is added. This reduction is due to redistributive elements such as caregiver credits provided through the statutory pension scheme. Results of a recentred influence functions (RIF) decomposition show that pension wealth reduces the gap substantially in the lower half of the distribution. At the 90th percentile, the gender wealth gap in net worth and in augmented wealth remains more stable at roughly 27-30%.