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In preclinical models, modification of experimental parameters associated with techniques of inducing subarachnoid hemorrhage (SAH) can greatly affect outcomes. To analyze how parameter choice affects the relevance and comparability of findings, we systematically reviewed 765 experimental studies of in vivo animal SAH models (2000-2014). During the last decade, we found marked increases in publications using smaller species and models for simulating acute events after SAH. Overall, the fewer types of species and models used did not correlate with an increased standardization in the experimental characteristics and procedures. However, by species, commonly applied, reliable parameters for each experimental SAH technique were identified in mouse, rat, rabbit, and dog models. Our findings can serve as a starting point for discussion toward a more uniform performance of SAH experiments, development of preclinical SAH common data elements, and establishment of standardized protocols for multicenter preclinical trials.

BACKGROUND AND PURPOSE:The purpose of this study was to assess nationwide incidence and outcomes of aneurysmal subarachnoid hemorrhage (aSAH). The Swiss SOS (Swiss Study on Subarachnoid Hemorrhage) was established in 2008 and offers the unique opportunity to provide this data from the point of care on a nationwide level. METHODS:All patients with confirmed aneurysmal subarachnoid hemorrhage admitted between January 1, 2009 and December 31, 2014, within Switzerland were recorded in a prospective registry. Incidence rates were calculated based on time-matched population data. Admission parameters and outcomes at discharge and at 1 year were recorded. RESULTS:We recorded data of 1787 consecutive patients. The incidence of aneurysmal subarachnoid hemorrhage in Switzerland was 3.7 per 100 000 persons/y. The number of female patients was 1170 (65.5%). With a follow-up rate of 91.3% at 1 year, 1042 patients (58.8%) led an independent life according to the modified Rankin Scale (0-2). About 1 in 10 patients survived in a dependent state (modified Rankin Scale, 3-5; n=185; 10.4%). Case fatality was 20.1% (n=356) at discharge and 22.1% (n=391) after 1 year. CONCLUSIONS:The current incidence of aneurysmal subarachnoid hemorrhage in Switzerland is lower than expected and an indication of a global trend toward decreasing admissions for ruptured intracranial aneurysms.REGISTRATION: URL: https://www.clinicaltrials.gov. Unique identifier: NCT03245866.

Objective: To analyze the Barrow Neurological Institute (BNI) grading scale, a quantitative scale measuring maximal subarachnoid hemorrhage thickness on axial computed tomography, on delayed cerebral ischemia (DCI) and outcome (modified Rankin scale; mRS) at discharge and 1-year follow-up (1FU) in patients with aneurysmal subarachnoid hemorrhage (aSAH) from a nationwide SAH registry. Methods All patient data was obtained from the Swiss nationwide multicentre registry database of aSAH (Swiss SOS). In 1321 patients demographic data, BNI scale, DCI and mRS up to the 1FU were available for descriptive and univariate statistics. Outcome was dichotomized in favorable (mRS 0-2) and unfavorable (mRS 3-6). Odds ratios (OR) for DCI of Fisher 3 patients (n=1115, 84%) compared to a control cohort of Fisher grade 1,2 and 4 patients (n=206, 16%) were calculated for each BNI grade separately. Results Overall, 409 patients (31 %) developed DCI with a high DCI rate in the Fisher 3 cohort (34%). For what concerns the BNI scale, DCI rates went up progressively from 26% (BNI 2) to 38% (BNI 5

BackgroundCell migration including collective cell movement and individual cell migration are crucial factors in embryogenesis. During the spreading/migration of cells, several types of adhesive structures physically interacting with the extracellular matrix (ECM) or with another cell have been described and the formation and maturation of adhesion structures are coordinated, however the molecular pathways involved are still not fully understood.ResultsWe generated a mouse embryonic fibroblast line (MEF) from homozygous mutant (Hectd1 R/R, Hectd1 Gt(RRC200)) mouse of the E3 ubiquitin ligase for inhibin B receptor (Hectd1). Detailed examination of cell motion on MEF cells demonstrated that loss of Hectd1 resulted in accelerated cell spreading and migration but impaired directionality of migration. In Hectd1 R/R cells paxillin and zyxin were largely mis-localized, whereas their expression levels were unchanged. In addition the formation of focal adhesions (FAs) was impaired and the focal complexes (FXs) were increased. We further identified HECTD1 as a key regulator of IQGAP1. IQGAP1 co-localized together with HECTD1 in the leading edge of cells. HECTD1 interacted with IQGAP1 and regulated its degradation through ubiquitination. Over-expression of IQGAP1 in control MEF phenocopied the spreading and migration defects of Hectd1 R/R cells. In contrast, siRNA-mediated knockdown of IQGAP1 rescued the defects in cellular movement of Hectd1 R/R cells.ConclusionsThe E3 ligase activity of Hectd1 regulates the protein level of IQGAP1 through ubiquitination and therefore mediates the dynamics of FXs including the recruitment of paxillin and actinin. IQGAP1 is one of the effectors of HECTD1.Electronic supplementary materialThe online version of this article (doi:10.1186/s12964-016-0156-8) contains supplementary material, which is available to authorized users.