Brain Plasticity Modulator p75 Neurotrophin Receptor in Human Urine after Different Acute Brain Injuries-A Prospective Cohort Study.

Acute brain injuries (ABIs) pose a substantial global burden, demanding effective prognostic indicators for outcomes. This study explores the potential of urinary p75 neurotrophin receptor (p75NTR) concentration as a prognostic biomarker, particularly in relation to unfavorable outcomes. The study involved 46 ABI patients, comprising sub-cohorts of aneurysmal subarachnoid hemorrhage, ischemic stroke, and traumatic brain injury. Furthermore, we had four healthy controls. Samples were systematically collected from patients treated at the University Hospital of Turku between 2017 and 2019, at early (1.50 ± 0.70 days) and late (9.17 ± 3.40 days) post-admission time points. Urinary p75NTR levels, measured by ELISA and normalized to creatinine, were compared against patients' outcomes using the modified Rankin Scale (mRS). Early urine samples showed no significant p75NTR concentration difference between favorable and unfavorable mRS groups. In contrast, late samples exhibited a statistically significant increase in p75NTR concentrations in the unfavorable group (p = 0.033), demonstrating good prognostic accuracy (AUC = 70.9%, 95% CI = 53-89%, p = 0.03). Assessment of p75NTR concentration changes over time revealed no significant variation in the favorable group (p = 0.992) but a significant increase in the unfavorable group (p = 0.009). Moreover, p75NTR concentration was significantly higher in ABI patients (mean ± SD 40.49 ± 28.83-65.85 ± 35.04 ng/mg) compared to healthy controls (mean ± SD 0.54 ± 0.44 ng/mg), irrespective of sampling time or outcome (p < 0.0001). In conclusion, late urinary p75NTR concentrations emerged as a potential prognostic biomarker for ABIs, showing increased levels associated with unfavorable outcomes regardless of the specific type of brain injury. While early samples exhibited no significant differences, the observed late increases emphasize the time-dependent nature of this potential biomarker. Further validation in larger patient cohorts is crucial, highlighting the need for additional research to establish p75NTR as a reliable prognostic biomarker across various ABIs. Additionally, its potential role as a diagnostic biomarker warrants exploration.

CXCR2-Blocking Has Context-Sensitive Effects on Rat Glioblastoma Cell Line Outgrowth (S635) in an Organotypic Rat Brain Slice Culture Depending on Microglia-Depletion (PLX5622) and Dexamethasone Treatment.

In glioblastoma (GBM), the interplay of different immune cell subtypes, cytokines, and/or drugs shows high context-dependencies. Interrelations between the routinely applied dexamethasone (Dex) and microglia remain elusive. Here, we exploited rat organotypic brain slice co-cultures (OBSC) to examine the effects on a rat GBM cell line (S635) outgrowth resulting from the presence of Dex and pretreatment with the colony-stimulating factor receptor 1 (CSF1-R) inhibitor PLX5622: in native OBSC (without PLX5622-pretreatment), a diminished S635 spheroid outgrowth was observable, whereas Dex-treatment enhanced outgrowth in this condition compared to PLX5622-pretreated OBSC. Screening the supernatants of our model with a proteome profiler, we found that CXCL2 was differentially secreted in a Dex- and PLX5622-dependent fashion. To analyze causal interrelations, we interrupted the CXCL2/CXCR2-axis: in the native OBSC condition, CXCR2-blocking resulted in increased outgrowth, in combination with Dex, we found potentiated outgrowth. No effect was found in the PLX5622-pretreated. Our method allowed us to study the influence of three different factors-dexamethasone, PLX5622, and CXCL2-in a well-controlled, simplified, and straight-forward mechanistic manner, and at the same time in a more realistic ex vivo scenario compared to in vitro studies. In our model, we showed a GBM outgrowth enhancing synergism between CXCR2-blocking and Dex-treatment in the native condition, which was levelled by PLX5622-pretreatment.

Declining Numbers of Neurosurgical Emergencies at a German University Medical Center during the Coronavirus Lockdown.

BACKGROUND: The coronavirus pandemic due to severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) is posing unprecedented challenges to health care systems around the globe. Consequently, various lockdown scenarios have been politically imposed to get control over the spread of this disease. We examined the impact of the lockdown situation on the number of neurosurgical emergency patients admitted to our tertiary care center with a catchment area of ∼2.2 million inhabitants in the south of Germany to ensure adequate neurosurgical emergency care during a pandemic lockdown. METHODS: All emergency admissions (with consecutive inpatient treatment) to the Department of Neurosurgery at the University Medical Center Regensburg, Germany, between March 1 and May 8 (69 days) of the years 2018, 2019, and 2020 were retrospectively identified and reviewed for this study. Demographic data, diagnoses, urgency of surgery, and duration of the journey to the emergency room were examined. RESULTS: Between March 1 and May 8, 2020, 59 emergency patients were neurosurgically treated at our department. Compared with 2018 and 2019, emergency admissions in 2020 had thus declined by 37.2 and 27.1%, respectively. Regarding the year 2020, we found a significant drop from 1.71 and 1.52 emergency patients per day in January and February 2020, respectively, to 0.86 during lockdown (p < 0.001). The decline especially concerned nontraumatic spinal cases and also patients with other neurosurgical diagnoses such as intracranial hemorrhage. Evaluation of the overall disease severity of admitted patients by means of the urgency of surgery showed no difference between the baseline years and the lockdown period. CONCLUSION: Our findings are in line with other observational studies of neurosurgical, neurologic, and cardiologic centers in Europe that have described a drop in emergency cases. The reasons for this drop that seems to affect various medical fields and countries across Europe are still unidentified. Morbidity and mortality rates are still unknown, and efforts should be made to facilitate neurosurgical emergency care during a pandemic lockdown.

Histological and SEM Assessment of Blood Stasis in Kidney Blood Vessels after Repeated Intra-Arterial Application of Radiographic Contrast Media.

BACKGROUND: After application of iodinated contrast media (CM), a pronounced deterioration of the microcirculation in skin and myocardium was reported. Clinically, the repeated application of CM, especially, led to an increase of the renal resistance index (RRI). With respect to the transiency of the RRI increase, it is reasonable to assume that the deterioration of blood flow could be due to transient blood stasis caused by reversible morphologic cell alterations due to osmotic discrepancies between CM and human blood. Therefore, the hypothesis was investigated whether CM are able to induce in vivo such blood stasis and cell deformations in the renal vasculature of well-hydrated pigs. METHODS: The in vivo study was performed as a prospective randomized examination to compare the effects of two different CM in 16 pigs (German Landrace). Pigs were randomized to receive either Iodixanol (n = 8), or Iopromide (n = 8). Each animal received 10 injections separated by 5-min intervals via the suprarenal aorta at a rate of 10 mL/s according to the usual procedure during a cardiac catheter examination. Finally, the kidneys were explanted and processed for histology (H & E staining and fibrin staining according to Weigert) as well as for scanning electron microscopy (SEM) with regards to morphologic correlates explaining the changes in the microcirculation. RESULTS: In each of the predefined four categories of vascular diameters, blood stasis were found, but clearly more often after application of Iopromide than after application of Iodixanol (p < 0.001). In addition, Iopromide induced more blood stasis in all of the examined kidney regions compared to Iodixanol (p = 0.0001). There were no obstructive events in the middle cortex following the application of Iodixanol. Except for the region around a puncture channel of a placed-in catheter probe, no fibrin was detected in Weigert's fibrin-stained samples, neither around the histologically assessed thrombi nor in vessels with blood stasis. Complementary SEM analyses revealed in a few cases only a slight generation of fibrin and thrombi and deformations, such as echinocyte and "box-like" deformations. CONCLUSIONS: According to previous in vitro studies, pathological erythrocyte deformations, such as echinocyte and box-like formation of erythrocytes, were observed also in vivo. In addition, blood stasis and/or thrombi could be detected in histological samples from explanted kidneys from young pigs after repeated in vivo administration of CM. In only a few cases, mural platelet aggregates within minimal fibrin meshes occurred only after the application of Iopromide.

Effect of iodinated contrast media on renal perfusion: A randomized comparison study in pigs using quantitative contrast-enhanced ultrasound (CEUS).

The administration of iodinated contrast media (CM) can cause microcirculatory disorder leading to acute renal dysfunction. In a prospective, randomized investigation two CM (Iodixanol vs Iopromide) were compared in 16 pigs. Each animal received 10 intra-aortal injections (5 ml Iodixanol or 4.32 ml Iopromide). Microcirculation was assessed using contrast-enhanced ultrasound (CEUS) directly on the kidney surface using time-to-peak (TTP) and blood-volume-analysis. Macroscopic observations were documented. Post mortem residual CM distribution in the kidneys was detected using X-ray. TTP was significantly prolonged over the descending vasa recta of the Iopromide group. This coincided with a visible marble-like pattern on the kidney surface occurring in 30 out of 80 Iopromide-injections but in 4 out of 80 Iodixanol-injections (p = 0.007). The blood volume over the entire kidney did not change after Iodixanol-application, but decreased by about 6.1% after Iopromide-application. The regional blood volume in the renal cortex showed a tendency to decrease by about 13.5% (p = 0.094) after Iodixanol-application, and clearly decreased by about 31.7% (p = 0.022) after Iopromide-application. The study revealed a consistent influence of repeated injections of two different CM on the kidney perfusion using three different imaging methods (CEUS analysis, macroscopic observation and X-ray analysis).