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Chondroitin sulfate proteoglycans (CSPGs) act as potent inhibitors of axonal growth and neuroplasticity after spinal cord injury (SCI). Here we reveal that CSPGs also play a critical role in preventing inflammation resolution by blocking the conversion of pro-inflammatory immune cells to a pro-repair phenotype in rodent models of SCI. We demonstrate that enzymatic digestion of CSPG glycosaminoglycans enhances immune cell clearance and reduces pro-inflammatory protein and gene expression profiles at key resolution time points. Analysis of phenotypically distinct immune cell clusters revealed CSPG-mediated modulation of macrophage and microglial subtypes which, together with T lymphocyte infiltration and composition changes, suggests a role for CSPGs in modulating both innate and adaptive immune responses after SCI. Mechanistically, CSPG activation of a pro-inflammatory phenotype in pro-repair immune cells was found to be TLR4-dependent, identifying TLR4 signalling as a key driver of CSPG-mediated immune modulation. These findings establish CSPGs as critical mediators of inflammation resolution failure after SCI in rodents, which leads to prolonged inflammatory pathology and irreversible tissue destruction.

OBJECTIVEMRI derived hippocampal volume (HV) and amyloid PET may be useful clinical biomarkers for differentiating between geriatric depression and Alzheimer’s Disease (AD). Here we investigated the incremental value of HV and 18F-flutemetmol PET in tandem and sequentially to improve discrimination in unclassified participants.METHODTwo approaches were compared in 41 participants with geriatric depression and 27 participants with probable AD: (1) amyloid and HV combined in one model and (2) HV first and then amyloid.RESULTSBoth HV(χ2(1) = 6.46: p= 0.011) and amyloid (χ2(1) =11.03: p=0.0009) were significant diagnostic predictors of depression (sensitivity: 95%, specificity: 89%). (2) 51% of participants were correctly classified according to clinical diagnosis based on HV alone, increasing to 87% when adding amyloid data (sensitivity: 94%, specificity: 78%).CONCLUSIONHippocampal volume may be a useful gatekeeper for identifying depressed individuals at risk for AD who would benefit from additional amyloid biomarkers when available.

BACKGROUND There is increasing clinical and scientific interest in electroconvulsive therapy (ECT). AIM To provideanoverviewofthe main research findingsofthe Flemish-Dutch research consortium ResPECT. METHOD We report on our review of the relevant literature. RESULTS Our studies confirm that ECT is one of the most efficient treatments for depression in later life and for depression with psychotic features. Older people with age-related brain pathology can respond well to ECT. It is still preferable to apply a standard pulse-width because this increases the efficacy of the treatment and minimises the cognitive impact. Even vulnerable older people can react favourably to ECT. CONCLUSION Recent findings of the ResPECT consortium are providing new insights that are applicable in daily clinical practice. Research into mechanisms of action can also increase our understanding of the pathophysiology of severe depression.

In vitro assessment of hormone receptor status using a ligand-binding assay or immunohistochemistry in breast cancer patients predicts endocrine responsiveness with an accuracy of only 60%-70%. Assessment of an end product of estrogen receptor stimulation, such as the progesterone receptor, is assumed to provide a measure of functional receptor content and has proven to increase predictive accuracy. In analogy with the estrogen-dependent regulation of somatostatin receptor (SSTR) expression in endocrine-responsive human breast cancer cell lines, efficient antiestrogen treatment in patients may result in a downregulation of SSTR at the cell surface in breast tumors. In vivo imaging of this molecular event by means of sequential (99m)Tc-depreotide scintigraphy could enable selection of breast cancer patients susceptible to endocrine therapy.Twenty patients with a diagnosis of advanced breast cancer in whom first- or second-line hormonal therapy was going to be initiated were included. Patients underwent sequential (99m)Tc-depreotide scintigraphy before and 3 wk after initiating hormonal treatment. Follow-up data were retrieved from routine clinical evaluation by means of physical examination, imaging (e.g., bone scan, CT, MRI) and blood analysis. Lesion-to-background ratios (L/BGs) were calculated on planar and SPECT images and a change of25% between the baseline and follow-up scan was considered significant.At 6 mo after initiation of treatment, 8 patients had stable disease and were considered to be responding to hormonal treatment, whereas 10 patients had progressive disease and were considered to be nonresponders. The positive and negative predictive values of baseline (99m)Tc-depreotide scintigraphy for endocrine responsiveness were 73% (8/11) and 100% (7/7), respectively. Sequential scans were always both positive or both negative. The relative change in (99m)Tc-depreotide uptake between sequential scans significantly differed in responders compared with nonresponders (P= 0.017)-uptake decreased in the first group and increased in the latter. As such, baseline (99m)Tc-depreotide scintigraphy combined with the changes in tracer uptake between the baseline and follow-up scan predicted endocrine responsiveness with an accuracy of 100%.Sequential (99m)Tc-depreotide scintigraphy could allow for separation of responders and nonresponders immediately or as early as 3 wk after initiation of treatment.

To explore a role for chemorepulsive axon guidance mechanisms in the regeneration of primary olfactory axons, we examined the expression of the chemorepellent semaphorin III (sema III), its receptor neuropilin-1, and collapsin response mediator protein-2 (CRMP-2) during regeneration of the olfactory system. In the intact olfactory system, neuropilin-1 and CRMP-2 mRNA expression define a distinct population of olfactory receptor neurons, corresponding to immature (B-50/GAP-43-positive) and a subset of mature (olfactory marker protein-positive) neurons located in the lower half of the olfactory epithelium. Sema III mRNA is expressed in pial sheet cells and in second-order olfactory neurons that are the target cells of neuropilin-1-positive primary olfactory axons. These data suggest that in the intact olfactory bulb sema III creates a molecular barrier, which helps restrict ingrowing olfactory axons to the nerve and glomerular layers of the bulb. Both axotomy of the primary olfactory nerve and bulbectomy induce the formation of new olfactory receptor neurons expressing neuropilin-1 and CRMP-2 mRNA. After axotomy, sema III mRNA is transiently induced in cells at the site of the lesion. These cells align regenerating bundles of olfactory axons. In contrast to the transient appearance of sema III-positive cells at the lesion site after axotomy, sema III-positive cells increase progressively after bulbectomy, apparently preventing regenerating neuropilin-1-positive nerve bundles from growing deeper into the lesion area. The presence of sema III in scar tissue and the concomitant expression of its receptor neuropilin-1 on regenerating olfactory axons suggests that semaphorin-mediated chemorepulsive signal transduction may contribute to the regenerative failure of these axons after bulbectomy.