ObjectivesFrom previous data in animal models of cerebral ischemia, lipocalin-2 (LCN2), a protein related to neutrophil function and cellular iron homeostasis, is supposed to have a value as a biomarker in ischemic stroke patients. Therefore, we examined LCN2 expression in the ischemic brain in an animal model and measured plasma levels of LCN2 in ischemic stroke patients.MethodsIn the mouse model of transient middle cerebral artery occlusion (tMCAO), LCN2 expression in the brain was analyzed by immunohistochemistry and correlated to cellular nonheme iron deposition up to 42 days after tMCAO. In human stroke patients, plasma levels of LCN2 were determined one week after ischemic stroke. In addition to established predictive parameters such as age, National Institutes of Health Stroke Scale and thrombolytic therapy, LCN2 was included into linear logistic regression modeling to predict clinical outcome at 90 days after stroke.ResultsImmunohistochemistry revealed expression of LCN2 in the mouse brain already at one day following tMCAO, and the amount of LCN2 subsequently increased with a maximum at 2 weeks after tMCAO. Accumulation of cellular nonheme iron was detectable one week post tMCAO and continued to increase. In ischemic stroke patients, higher plasma levels of LCN2 were associated with a worse clinical outcome at 90 days and with the occurrence of post-stroke infections.ConclusionsLCN2 is expressed in the ischemic brain after temporary experimental ischemia and paralleled by the accumulation of cellular nonheme iron. Plasma levels of LCN2 measured in patients one week after ischemic stroke contribute to the prediction of clinical outcome at 90 days and reflect the systemic response to post-stroke infections.

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The role of astrocytes in the pathophysiology of multiple sclerosis (MS) is discussed controversially. Especially the formation of the glial scar is often believed to act as a barrier for remyelination. At the same time, astrocytes are known to produce factors that influence oligodendrocyte precursor cell (OPC) survival. To explore these mechanisms, we investigated the astrocytic reaction in an animal model induced by immunization with myelin oligodendrocyte glycoprotein (MOG) in Dark Agouti (DA) rats, which mimics most of the histological features of MS. We correlated the astroglial reaction by immunohistochemistry (IHC) for glial fibrillary acidic protein (GFAP) to the remyelination capacity by in situ hybridization for mRNA of proteolipid protein (PLP), indicative of OPCs, over the full course of the disease. PLP mRNA peaked in early remyelinating lesions while the amount of GFAP positive astrocytes was highest in remyelinated lesions. In shadow plaques, we found at the same time all features of a glial scar and numbers of OPCs and mature oligodendrocytes, which were nearly equal to that in unaffected white matter areas. To assess the plaque environment, we furthermore quantitatively analyzed factors expressed by astrocytes previously suggested to influence remyelination. From our data, we conclude that remyelination occurs despite an abundant glial reaction in this animal model. The different patterns of astrocytic factors and the occurrence of different astrocytic phenotypes during lesion evolution furthermore indicate a finely regulated, balanced astrocytic involvement leading to successful repair.

Purpose In magnetic resonance elastography (MRE), a series of time‐shifted images is acquired at specific phase offsets in relation to an induced mechanical excitation. To efficiently gather the set of phase offset images and to overcome limitations due to prolonged TEs and related susceptibility artifacts at low‐frequency MRE, we developed an improved displacement encoding with a stimulated echoes (DENSE) method. Methods The proposed multiphase DENSE‐MRE acquisition scheme allows full sampling of the wave propagation in 1 encoding direction during each TR using multiple readouts at specific phase offsets. With this approach, all phase offsets can be imaged in 1 TR without the need for whole sequence repetitions at time‐shifted offsets relative to the excitation motion. We tested this technique in phantom experiments with 60 Hz and in the brain of 4 volunteers using 20‐Hz harmonic excitation. Results Three‐dimensional wave propagation could be acquired in 7 minutes 30 seconds. Following background phase elimination, clear wave images were obtained, showing the propagation of the waves over time. Calculated shear modulus maps of the phantom matched well to the maps obtained by conventional gradient‐echo MRE. In the brain, low‐frequency DENSE‐MRE images were free of susceptibility‐induced artifacts and the calculated maps showed a median global complex shear modulus magnitude of 0.72 kPa and phase angle of 1.03 rad across volunteers. Conclusion The proposed multiphase DENSE approach allows efficient low‐frequency MRE with short TEs and is well‐suited for low‐frequency MRE of the human brain.

Anti-myelin oligodendrocyte glycoprotein (MOG) antibodies (MOG-Abs) are commonly associated with clinical presentations as acute disseminated encephalomyelitis (ADEM) in both adults and children and anti-aquaporin 4 antibody-seronegative neuromyelitis optica spectrum disorder (NMOSD) and related syndromes such as optic neuritis, myelitis, and brainstem encephalitis. Most often, the presence of MOG-Abs is associated with a more benign clinical course and a good response to steroids. Here, we present a case report of a previously healthy 52-year-old female patient with fulminant demyelinating encephalitis, leading to death within a week after the first presenting symptoms from a massive brain edema irresponsive to high-dose intravenous steroids as well as osmotic therapy. The final diagnosis was only made postmortem after serum anti-MOG-Abs results were available. Histopathological analysis of the brain revealed extensive, predominantly cortical demyelinating lesions in the frontal, temporal, and parietal lobes with intracortical, leukocortical, and subpial plaques, associated with pronounced perivenous deposition of activated complement complex as well as features of acute MS characterized by destructive lesions.A 52-year-old woman, a cashier at a supermarket, presented in our outpatient department with difficulties in speaking. Furthermore, she complained of headache in the last 2 weeks. At neurological examination, she showed features of an encephalitic syndrome (disorientation, agitation, poor memory functioning) and continuously perseverated the same sentences. Gaze was preferable to the right, but there were no motor signs on admittance. Meningeal signs were positive. Past medical history was remarkable for hypothyreodism, a previous gastric-banding surgery in 2011, and depression. She was on a permanent antidepressive medication (Sertralin/Trazodon) as well as thyroid hormone replacement. Allergies were documented against Diclofenac and Penicillin.An initially performed CT of the brain (CCT) revealed a newly formed hypodensity in the left occipital region, which was not present on an archival CCT scan from the year before. A subsequently performed MRI of the brain furthermore revealed multiple, contrast-enhancing