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The choroid plexus epithelium (CPE) has served as a model-epithelium for cell polarization and transport studies and plays a crucial role for cerebrospinal fluid (CSF) production. The normal luminal membrane expression of Na+,K+-ATPase, aquaporin-1 and Na+/H+ exchanger 1 in the choroid plexus is severely affected by deletion of the slc4a10 gene that encodes the bicarbonate transporting protein Ncbe/NBCn2. The causes for these deviations from normal epithelial polarization and redistribution following specific gene knockout are unknown, but may be significant for basic epithelial cell biology. Therefore, a more comprehensive analysis of cell polarization in the choroid plexus is warranted. We find that the cytoskeleton in the choroid plexus contains αI-, αII-, βI-, and βII-spectrin isoforms along with the anchoring protein ankyrin-3, most of which are mainly localized in the luminal membrane domain. Furthermore, we find α-adducin localized near the plasma membranes globally, but with only faint expression in the luminal membrane domain. In slc4a10 knockout mice, the abundance of β1 Na+,K+-ATPase subunits in the luminal membrane is markedly reduced. Anion exchanger 2 abundance is increased in slc4a10 knockout and its anchor protein, α-adducin is almost exclusively found near the basolateral domain. The αI- and βI-spectrin abundances are also decreased in the slc4a10 knockout, where the basolateral domain expression of αI-spectrin is exchanged for a strictly luminal domain localization. E-cadherin expression is unchanged in the slc4a10 knockout, while small decreases in abundance are observed for its probable adaptor proteins, the catenins. Interestingly, the abundance of the tight junction protein claudin-2 is significantly reduced in the slc4a10 knockouts, which may critically affect paracellular transport in this epithelium. The observations allow the generation of new hypotheses on basic cell biological paradigms that can be tested experimentally in future studies.

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BackgroundNeurofilament light chain (NfL) is a neuron-specific biomarker with prognostic ability in several types of central nervous system injuries. This study investigates if plasma NfL (pNfL) is elevated early after spontaneous intracerebral hemorrhage (ICH) and whether such elevation reflects disease severity and day-30 outcome.MethodspNfL was quantified by single molecule array analysis in 103 reference subjects (RS) and in samples from 37 patients with ICH obtained on admission to hospital and at 24-h follow-up. The primary outcome was day-30 mortality. Clinical status on admission was evaluated by standardized scoring systems.ResultsMedian pNfL among RS was 9.6 (interquartile range [IQR] 6.2) pg/mL. Upon admission, ICH patients had pNfL of 19.8 (IQR 30.7) pg/mL increasing to 35.9 (IQR 44.5) pg/mL at 24 h (all, p < 0.001). On admission, pNfL was higher among ICH non-survivors than survivors (119.2 [IQR 152.6] pg/mL vs. 15.7 [IQR 19.6] pg/mL, p < 0.01) and this difference was observed also on 24 h follow-up (195.1 [IQR 73.9] pg/mL vs. 31.3 [IQR 27.8] pg/mL, p < 0.01). The area under the receiver operating characteristic curve (ROC AUC) for discrimination of day-30 mortality was significant on admission (AUC = 0.83, 95% confidence interval [CI]: 0.56–1.0) and increased on 24-h follow-up (AUC = 0.93, 95% CI: 0.84–1.0). The odds ratio (OR) for death, by each quartile increase in pNfL was significant both on admission (OR = 4.52, 95% CI: 1.32–15.48) and after 24-h follow-up (OR = 9.52, 95% CI: 1.26–71.74).ConclusionsPNfL is associated with day-30 mortality after spontaneous ICH when early after the ictus.

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Previous research indicates that the complement system is activated after occurrence of intracerebral hemorrhage (ICH) and spontaneous subarachnoid hemorrhage (SAH). The role of the lectin pathway (LP) of the complement system in this activation has only scarcely been investigated. The aim of this study was to determine the plasma concentration of the LP proteins in patients with ICH or SAH at admission compared to healthy individuals. Secondly, ICH and SAH patients were followed during the initial 24 h of disease, to investigate changes in LP protein concentrations during the critical acute phase. This prospective, observational study included 30 ICH and 33 SAH patients. EDTA plasma samples were collected at admission, 6 and 24 h after symptom onset. Time-resolved immuno-flourometric assays (TRIFMA) were used to measure all proteins of the LP in patient samples and in samples from age- and gender-matched healthy individuals. Compared to healthy individuals, ICH and SAH patients had increased levels of H-ficolin (p = 0.04, p = 0.03), M-ficolin (both p < 0.0001), and MAp44 (both p = 0.01) at admission. M-ficolin, H-ficolin, CL-L1, MASP-1, MASP-3, and MAp44 decreased significantly in both ICH and SAH patients during the initial 24 h after symptom onset. In conclusion, we observed significant differences in lectin pathway protein concentrations between patients with ICH or SAH and healthy individuals. Significant dynamics in lectin pathway protein levels were demonstrated during the initial 24 h after symptom onset. This indicates a potential role of the LP proteins during the acute phase of SAH and ICH.