Changes in nationwide in-hospital stroke care during the first four waves of COVID-19 in Germany.

Introduction: In the early stages of the global COVID-19 pandemic hospital admissions for acute ischemic stroke (AIS) decreased substantially. As health systems have become more experienced in dealing with the pandemic, and as the proportion of the population vaccinated rises, it is of interest to determine whether the prevalence of AIS hospitalization and outcomes from hospitalization have returned to normal.

Patients And Methods: In this observational, retrospective cohort study, we compared the prevalence and outcomes of AIS during the first four waves of the pandemic to corresponding pre-pandemic periods in 2019 using administrative data collected from a nationwide network of 76 hospitals that manages 7% of all in-hospital cases in Germany.

Reversal learning reveals cognitive deficits and altered prediction error encoding in the ventral striatum in Huntington's disease.

Huntington's disease (HD) is an autosomal dominant neurodegenerative condition characterized by a triad of movement disorder, neuropsychiatric symptoms and cognitive deficits. The striatum is particularly vulnerable to the effects of mutant huntingtin, and cell loss can already be found in presymptomatic stages. Since the striatum is well known for its role in reinforcement learning, we hypothesized to find altered behavioral and neural responses in HD patients in a probabilistic reinforcement learning task performed during functional magnetic resonance imaging.

Preventive antibacterial therapy in acute ischemic stroke: a randomized controlled trial.

Background: Pneumonia is a major risk factor of death after acute stroke. In a mouse model, preventive antibacterial therapy with moxifloxacin not only prevents the development of post-stroke infections, it also reduces mortality, and improves neurological outcome significantly. In this study we investigate whether this approach is effective in stroke patients.

Inducible nitric oxide synthase does not mediate brain damage after transient focal cerebral ischemia in mice.

Nitric oxide produced by the inducible nitric oxide synthase (iNOS) is believed to participate in the pathogenic events after cerebral ischemia. In this study, we examined the expression of iNOS in the brain after transient focal cerebral ischemia in mice. We detected differential expression of exons 2 and 3 of iNOS mRNA (16-fold upregulation at 24 to 72 h after middle cerebral artery occlusion, MCAO) compared with exons 6 to 8, 12 to 14, 21 to 22, and 26 to 27 (2- to 5-fold upregulation after 72 and 96 h), which would be compatible with alternative splicing.

Protection from brain damage and bacterial infection in murine stroke by the novel caspase-inhibitor Q-VD-OPH.

Infarction size and infections are important determinants of stroke outcome in humans. Bacterial infections are promoted by stroke-induced immunodeficiency which in experimental stroke is mainly characterized by extensive lymphocyte apoptosis and dysfunction. Pharmacological inhibition of caspases may improve stroke outcome not only by reducing apoptotic brain damage but also by attenuating stroke-induced immunodeficiency.

Stroke-induced immunodepression: experimental evidence and clinical relevance.

Stroke affects the normally well-balanced interplay of the 2 supersystems: the nervous and the immune system. Recent research elucidated some of the involved signals and mechanisms and, importantly, was able to demonstrate that brain-immune interactions are highly relevant for functional outcome after stroke. Immunodepression after stroke increases the susceptibility to infection, the most relevant complication in stroke patients.

Stroke propagates bacterial aspiration to pneumonia in a model of cerebral ischemia.

Background And Purpose: Bacterial pneumonia is the most common cause of death in patients sustaining acute stroke and is believed to result from an increased aspiration. Recently, stroke-induced immunodeficiency was described in a mouse model of cerebral ischemia, which is primarily caused by overactivation of sympathetic nervous system. We tested if stroke-induced immunodeficiency increases the risk of pneumonia after aspiration in a newly developed model of poststroke pneumonia.

Improved reperfusion and neuroprotection by creatine in a mouse model of stroke.

Stroke leads to energy failure and subsequent neuronal cell loss. Creatine and phosphocreatine constitute a cellular energy buffering and transport system, and dietary creatine supplementation was shown to protect neurons in several models of neurodegeneration. Although creatine has recently been found to reduce infarct size after cerebral ischemia in mice, the mechanisms of neuroprotection remained unclear.

Central nervous system injury-induced immune deficiency syndrome.

Infections are a leading cause of morbidity and mortality in patients with acute CNS injury. It has recently become clear that CNS injury significantly increases susceptibility to infection by brain-specific mechanisms: CNS injury induces a disturbance of the normally well balanced interplay between the immune system and the CNS. As a result, CNS injury leads to secondary immunodeficiency - CNS injury-induced immunodepression (CIDS) - and infection.

Preventive antibacterial treatment improves the general medical and neurological outcome in a mouse model of stroke.

Background And Purpose: Epidemiological studies have demonstrated a high incidence of infections after severe stroke and their prominent role in morbidity and mortality in stroke patients. In a mouse model, it has been shown recently that stroke is coupled with severe and long-lasting immunosuppression, which is responsible for the development of spontaneous systemic infections. Here, we investigated in the same model the effects of preventive antibiotic treatment on survival and functional outcome of experimental stroke.

Stroke-induced immunodeficiency promotes spontaneous bacterial infections and is mediated by sympathetic activation reversal by poststroke T helper cell type 1-like immunostimulation.

Infections are a leading cause of death in stroke patients. In a mouse model of focal cerebral ischemia, we tested the hypothesis that a stroke-induced immunodeficiency increases the susceptibility to bacterial infections. 3 d after ischemia, all animals developed spontaneous septicemia and pneumonia.

Bone marrow-derived cells expressing green fluorescent protein under the control of the glial fibrillary acidic protein promoter do not differentiate into astrocytes in vitro and in vivo.

Differentiation of bone marrow (BM) cells into astroglia expressing the glial fibrillary acidic protein (GFAP) has been reported in vitro and after intracerebral or systemic BM transplantation. In contrast, recent data suggest that astrocytic differentiation does not occur from BM-derived cells in vivo. Using transgenic mice that express the enhanced green fluorescent protein (GFP) under the control of the human glial fibrillary acidic protein (GFAP) promoter, we investigated the potential of adult murine BM-derived cells to differentiate into macroglia.

Hypoxia-induced stroke tolerance in the mouse is mediated by erythropoietin.

Background And Purpose: Cellular response to hypoxia is mainly controlled by hypoxia-inducible factor 1 (HIF-1). The HIF-1 target gene erythropoietin (EPO) has been described as neuroprotective. Thus, we hypothesize EPO to be an essential mediator of protection in hypoxic preconditioning.

Isoflurane induced prolonged protection against cerebral ischemia in mice: a redox sensitive mechanism?

We here demonstrate that general anesthesia with isoflurane can have profound effects on the brain of mice long after the anesthetic has been discontinued. Three hours of exposure to 1% isoflurane induced rapid and longlasting protection against 60 min transient focal cerebral ischemia induced by filament occlusion of the middle cerebral artery (MCAO). Mean infarct volumes were significantly smaller in animals pretreated with isoflurane 0, 12, and 24 h before MCAO (-38%, -31%, -24%, respectively).

Serial analysis of gene expression identifies metallothionein-II as major neuroprotective gene in mouse focal cerebral ischemia.

We applied serial analysis of gene expression (SAGE) to study differentially expressed genes in mouse brain 14 hr after the induction of focal cerebral ischemia. Analysis of >60,000 transcripts revealed 83 upregulated and 94 downregulated transcripts (more than or equal to eightfold). Reproducibility was demonstrated by performing SAGE in duplicate on the same starting material.

Desferrioxamine induces delayed tolerance against cerebral ischemia in vivo and in vitro.

The widely prescribed drug desferrioxamine is a known activator of the hypoxia-inducible transcription factor 1 (HIF-1) and the subsequent transcription of erythropoietin. In the brain, HIF-1 is a master switch of the transcriptional response to hypoxia, whereas erythropoietin is a potent neuroprotectant. The authors show that desferrioxamine dose-dependently and time-dependently induces tolerance against focal cerebral ischemia in rats and mice, and against oxygen-glucose deprivation in purified cortical neurons.