Hypoxia triggers reactive microglial inflammation and lipid droplet (LD) accumulation under stroke conditions, although the mutual interactions between these two processes are insufficiently understood. Hence, the involvement of transforming growth factor (TGF)-β1 in inflammation and LD accumulation in cultured microglia exposed to hypoxia were analyzed herein. Primary microglia were exposed to oxygen-glucose deprivation (OGD) injury and lipopolysaccharide (LPS) stimulation. For analyzing the role of TGF-β1 patterns under such conditions, a TGF-β1 siRNA and an exogenous recombinant TGF-β1 protein were employed. Further studies applied Triacsin C, an inhibitor of LD formation, in order to directly assess the impact of LD formation on the modulation of inflammation. To assess mutual microglia-to-neuron interactions, a co-culture model of these cells was established. Upon OGD exposure, microglial TGF-β1 levels were significantly increased, whereas LPS stimulation yielded decreased levels. Elevating TGF-β1 expression proved highly effective in suppressing inflammation and reducing LD accumulation in microglia exposed to LPS. Conversely, inhibition of TGF-β1 led to the promotion of microglial cell inflammation and an increase in LD accumulation in microglia exposed to OGD. Employing the LD formation inhibitor Triacsin C, in turn, polarized microglia towards an anti-inflammatory phenotype. Such modulation of both microglial TGF-β1 and LD levels significantly affected the resistance of co-cultured neurons. This study provides novel insights by demonstrating that TGF-β1 plays a protective role against microglia-mediated neuroinflammation through the suppression of LD accumulation. These findings offer a fresh perspective on stroke treatment, suggesting the potential of targeting this pathway for therapeutic interventions.

Despite clear evidence for the effectiveness of oral anticoagulation (OA) in patients with atrial fibrillation (AF), there is evidence for the underutilisation of this therapy in the secondary stroke prevention. We therefore investigate the link between the use of OA in stroke patients with AF and favourable clinical outcome following the acute event. The study population was determined by identifying the overlap of two different databases: a stroke registry and claims data of a health insurance company. Baseline data originated from the registry; documented dementia and the prescriptions for OA were derived from the insurance database. Patients with AF, minor physical impairment, and evidence of more than 30 days without further hospitalisation within the subsequent 90 days after the acute event were selected for the analysis. 1828 patients were selected (mean age 77.6 years), 1064 patients (58.2%) were female. 827 patients (45%) received a prescription for OA. The following factors were independently associated with no prescription for oral anticoagulants: increased age (OR: 0.54, CI: 0.46-0.63; P < 0.0001), female sex (OR: 0.77, CI: 0.63-0.94; P < 0.011), worsening disability status at discharge (OR: 0.88, CI: 0.81-0.96; P < 0.006), and documented dementia (OR: 0.54, CI: 0.39-0.73; P < 0.001). Conversely, treatment in a neurological department was associated with prescription for OA (OR: 1.47, CI: 1.19-1.81; P < 0.003). In more than half of the patients with AF who suffered a stroke OA was not prescribed. The factors associated with reluctance in prescribing anticoagulants are increasing age, female sex, treatment at a non-neurological department, worsening disability, and dementia.

Neuromyelitis optica (NMO) is an autoimmune disorder of the central nervous system, which is characterized by autoantibodies directed against the water channel aquaporin-4 (AQP4). As one of the main water regulators in the central nervous system, APQ4 is supposed to be involved in the dynamics of brain edema. Cerebral edema seriously affects clinical outcome after ischemic stroke; we therefore aimed to investigate whether NMO-antibodies may exert the same functional effects as an AQP4-inhibitor in-vivo in acute ischemic stroke. Sixteen male Wistar rats were randomized into two groups twice receiving either purified NMO-IgG or immune globulin from healthy controls, 24 hours and 30 minutes before middle cerebral artery occlusion (MCAO) was performed. T2-weighted MRI was carried out 24 hours after MCAO. MRI-examination showed a significant increase of infarct size in relation to the cerebral hemisphere volume with NMO-IgG treated animals (27.1% ± 11.1% vs. 14.3% ± 7.2%; p < 0.05) when corrected for the space-occupying effect of vasogenic edema formation and similar results without edema correction (34.4% ± 16.4% vs. 17.5% ± 9.3%; p < 0.05). Furthermore, T2-RT revealed a significant increase in cortical brain water content of the treatment group (19.5 ms ± 9.7 ms vs. 9.2 ms ± 5.2 ms; p < 0.05). These results support the functional impact of NMO-antibodies and also offer an in-vivo-applicable animal model to investigate the properties of AQP4 in ischemic stroke.