Spreading depolarization (SD) describes a propagating neuronal mass depolarization within the cerebral cortex that represents a mediator of infarct development and strongly stimulates the metabolic rate of O₂ consumption. Here, we investigated the influence of Spreading Depolarization (SD) on brain tissue partial pressure of O₂ (ptiO₂) within the peri-infarct tissue of patients suffering malignant hemispheric stroke (MHS). This prospective observational trial included 25 patients with MHS that underwent decompressive hemicraniectomy followed by subdural placement of electrodes for electrocorticography (ECoG) and neighboring implantation of a ptiO₂ probe within the peri-infarcted cortex. Continuous side-by-side ECoG + ptiO₂ recordings were obtained for 3-6 days postoperatively and analyzed for the occurrence of SD-independent and SD-coupled ptiO₂ changes, radiological findings, as well as their association with clinical outcome at 6 months. During the combined ECoG + ptiO₂ monitoring period of 2,604 hours and among 1,022 SDs, 483 (47%) SD-coupled ptiO₂ variations were identified as biphasic (59%), hypoxic (36%) or hyperoxic (5%) ptiO₂ responses that differed significantly (*p<0.0001). Among the remaining 538/1,022 (53%) SDs, no SD-coupled ptiO₂ response was detected, which we categorized as ‘No response’. The overall infarct progression was 1.7% (IQR -2.5–10.9). Spreading Depolarization characteristics regarding type, duration and frequency, as well as SD-independent baseline ptiO₂ had no association with outcome. In contrast, a high occurrence rate and amplitude of SD-coupled variations in ptiO₂ were associated with improved outcome at 6 months (occurrence: r=-0.62, *p=0.035; amplitude: r=-0.57, *p=0.024; Spearman correlation). In conclusion, an absent or reduced ptiO₂ response to SD could indicate tissue-at-risk and help direct targeted treatment strategies in ischemic stroke, which is further evidence that not all SDs are the same, but that tissue responses coupled to SD such as ptiO₂ contain prognostic information. In particular, a lack of SD-coupled ptiO₂ variations appears to be a predictor of worse outcome in large hemispheric stroke.

Endothelial cells (ECs) have gained an increased scientific focus since they were reported to provide guidance for Schwann cells and subsequently following axons after nerve injuries. However, previous protocols for the isolation of nerve-derived ECs from human nerves are ineffective regarding time and yield. Therefore, we established a novel and efficient protocol for the isolation of ECs from human peripheral nerves by means of immunomagnetic CD31-antibody conjugated Dynabeads and assessed the purity of the isolated cells. The easy-to-follow and time-effective isolation method allows the isolation of > 95% pure ECs. The isolated ECs were shown to express highly specific EC marker proteins and revealed functional properties by formation of CD31 and VE-cadherin positive adherens junctions, as well as ZO-1 positive tight-junctions. Moreover, the formation of capillary EC-tubes was observed in-vitro. The novel protocol for the isolation of human nerve-derived ECs allows and simplifies the usage of ECs in research of the human blood-nerve-barrier and peripheral nerve regeneration. Additionally, a potential experimental application of patient-derived nerve ECs in the in-vitro vascularization of artificial nerve grafts is feasible.

BACKGROUND: Clinical and electrophysiological assessments prevail in evaluation of traumatic nerve lesions and their regeneration following nerve surgery in humans. Recently, high-resolution neurosonography (HRNS) and magnetic resonance neurography have gained significant importance in peripheral nerve imaging. The use of the grey-scale-based “fascicular ratio” (FR) was established using both modalities allowing for quantitative assessment. OBJECTIVE: To find out whether FR using HRNS can assess nerve trauma and structural reorganization in correlation to postoperative clinical development. METHODS: Retrospectively, 16 patients with operated traumatic peripheral nerve lesions were included. The control group consisted of 6 healthy volunteers. All imaging was performed with a 15 to 6 MHz ultrasound probe (SonoSite X-Porte; Fujifilm, Tokyo, Japan). FR was calculated using Fiji (兠) on 8-bit-images (“MaxEntropy” using “Auto-Threshold” plug-in). RESULTS: Thirteen of 16 patients required autologous nerve grafting and 3 of 16 extra-intraneural neurolysis. There was no statistical difference between the FR of nonaffected patients’ nerve portion with 43.48% and controls with FR 48.12%. The neuromatous nerve portion in grafted patients differed significantly with 85.05%. Postoperatively, FR values returned to normal with a mean of 39.33%. In the neurolyzed patients, FR in the affected portion was 78.54%. After neurolysis, FR returned to healthy values (50.79%). Ten of 16 patients showed clinical reinnervation. CONCLUSION: To our best knowledge, this is the first description of FR using HRNS for quantitative assessment of nerve damage and postoperative structural reorganization. Our results show a significant difference in healthy vs lesioned nerves and a change in recovering nerve portions towards a more “physiological” ratio. Further evaluation in larger patient groups is required.

BACKGROUND: Spreading depolarization describes a near-complete electrical discharge with altered local cerebral blood flow. It is described in association with acute and chronic diseases like hemorrhagic stroke or migraine. Moyamoya vasculopathy is a chronic, progressive cerebrovascular disorder leading to cerebral hypoperfusion, hemodynamically insufficient basal collateralization, and increased cortical microvascularization. METHODS: In a prospective case series, we monitored for spontaneous spreading depolarization activity by using intraoperative laser speckle imaging for real-time visualization and measurement of cortical perfusion and cerebrovascular reserve capacity during cerebral revascularization in 4 consecutive patients with moyamoya. RESULTS: Spontaneous spreading depolarization occurrence was documented in a patient with moyamoya before bypass grafting. Interestingly, this patient also exhibited a marked preoperative increase in angiographic collateral vessel formation. CONCLUSIONS: The spontaneous occurrence of SDs in moyamoya vasculopathy could potentially provide an explanation for localized cortical infarction and increased cortical microvascular density in these patients.

Aneurysmal subarachnoid hemorrhage (aSAH) has a high complications burden, with in-hospital mortality as the most devastating outcome. We aimed to develop and validate a risk score for early prediction of in-hospital mortality after aSAH. Data from 2 university hospitals were pooled (n = 1070), with cohorts for score construction (n = 886) and external validation (n = 184). Several parameters assessable at admission were collected. Independent predictors of in-hospital mortality were used as mortality score components. Diagnostic accuracy of the novel score was compared to the Hunt and Hess Age, Intraventricular Hemorrhage, Rebleed and World Federation of Neurosurgical Societies (WFNS) scores. Overall rate of in-hospital mortality was 19% and 14.7% in construction and validation cohorts, respectively. The novel risk score (aSAH mortality score: 0-12 points) included patients' age (≤55 years: 0 points, 56-70 years: 1 point, >70 years: 2 points), aneurysm rebleeding (2 points), WFNS grade (grade I-II: 0 points, grade III-IV: 2 points, grade V: 5 points), and Hijdra sum score (≤10: 0 points, 11-20: 1 point, 21-30: 2 points, >30: 3 points). In-hospital mortality rates ranged 0.6% (0 points) to 100% (12 points) in the construction cohort, and 0% (0 points) to 60% (10 points) in the validation cohort. In the receiver operating characteristic analysis, the aneurysmal subarachnoid hemorrhage mortality score (area under the curve [AUC]: 0.829 and 0.824 in the construction and validation cohorts, respectively) was superior to the Hunt and Hess Age, Intraventricular Hemorrhage, Rebleed (AUC: 0.811 and 0.813) and WFNS scores (AUC: 0.768 and 0.795). Risk of in-hospital mortality after aSAH can be predicted with high accuracy using baseline characteristics. The novel risk score showed best diagnostic performance in the construction and validation cohorts and can aid in early prognostication and treatment decisions.