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• 3-MA improved the basal physiological status of mice with SAE. • 3-MA relieved symptoms and manifestations of acute encephalopathy. • 3-MA reduced neuroinflammation by suppressing glial cell activation and neuronal damage. • 3-MA alleviated cognitive impairment by inhibiting autophagy. Sepsis-associated encephalopathy (SAE) can lead to severe cerebral dysfunction as well as cognitive dysfunction, resulting in a significant disease burden. 3-Methyladenine (3-MA) has been confirmed to have anti-inflammatory effects on diseases characterized by enhanced autophagy. However, its role in SAE has not been clarified. An SAE mouse model was generated by intraperitoneal injection of lipopolysaccharide (LPS). Mice were given 5, 20, or 80 mg/kg 3-MA to determine the therapeutic dose. The mice in the different groups were given 20 mg/kg 3-MA or saline, and survival, body temperature, body weight and neurobehavioral scores were measured at different time points. The expression of autophagy-related proteins and inflammatory factors was detected by Western blotting, enzyme linked immunosorbent assay (ELISA) and real-time quantitative polymerase chain reaction (RT–qPCR) 12 h after LPS induction. Glial activation and neuronal injury in the hippocampus were detected by immunofluorescence staining and HE staining. The open Field test, novel object recognition (NOR) test, Y-maze test, and Morris water maze (MWM) test were performed to assess cognitive function. Treatment with 20 or 80 mg/kg 3-MA reduced the increase in hippocampal TNF-α, IL-6, and IL-1β expression in SAE model mice, with 20 mg/kg 3-MA having the greatest therapeutic effect. Treatment with 20 mg/kg 3-MA effectively reduced the expression of hippocampal autophagy-related proteins and mortality, ameliorated hypothermia, decreased body weight and electroencephalography (EEG) performance, and attenuated the activation of neuroglia and neuronal damage. Moreover, it alleviated the cognitive dysfunction 2 weeks after LPS induction. 3-MA reduced neuroglial activation and neuronal damage, attenuated neuroinflammation, and improved cognitive deficits during recovery period by inhibiting autophagy in SAE. [ABSTRACT FROM AUTHOR]

This work was aimed to study the risk factors and prognostic treatment for acute ischemic stroke (AIS) patients with early neurological deterioration (END) after intravenous thrombolytic therapy via compressed sensing algorithm-based magnetic resonance imaging (CS-MRI). 231 patients who were diagnosed with AIS were selected, and the final involved number of patients was 182. Patients with AIS were treated with intravenous thrombolysis with alteplase within 4.5 hours of onset. After treatment, patients with early neurological deterioration were defined as the deteriorating group and those without early neurological impairment were defined as the nondeteriorating group. In univariate analysis, hypertension, white blood cell count, and National Institutes of Health Stroke Scale (NIHSS) score were correlated with the occurrence of END. Under the CS-MRI theory, the two groups of patients were evaluated for middle cerebral artery basal ganglia infarction and internal watershed infarction. After univariate analysis, the P < 0.1 variables were taken as the independent variable, and the binary logistic regression model was adopted for multivariate regression analysis. It was disclosed that NIHSS score was not correlated with the occurrence of early neurological function deterioration, while homocysteine was. Hypertension, white blood cell count, homocysteine, and NIHSS score were risk factors for END. The image analysis revealed that the incidence of deteriorating basal ganglia infarction group was lower relative to the nondeteriorating group, and the incidence of watershed infarction was higher in the deteriorating group versus the nondeteriorating group. The image analysis suggested that predicting the occurrence of END through risk factors can actively provide endovascular treatment for patients with AIS. [ABSTRACT FROM AUTHOR]

Neuroinflammation contributes to the generation of epilepsy and has been proposed as an effective therapeutic target. Recent studies have uncovered the potential effects of the anti-fungal drug miconazole for treating various brain diseases by suppressing neuroinflammation but have not yet been studied in epilepsy. Here, we investigated the effects of different doses of miconazole (5, 20, 80 mg/kg) on seizure threshold, inflammatory cytokines release, and glial cells activation in the pilocarpine (PILO) pentylenetetrazole (PTZ), and intrahippocampal kainic acid (IHKA) models. We demonstrated that 5 and 20 mg/kg miconazole increased seizure threshold, but only 20 mg/kg miconazole reduced inflammatory cytokines release, glial cells activation, and morphological alteration during the early post-induction period (24 h, 3 days). We further investigated the effects of 20 mg/kg miconazole on epilepsy (4 weeks after KA injection). We found that miconazole significantly attenuated cytokines production, glial cells activation, microglial morphological changes, frequency and duration of recurrent hippocampal paroxysmal discharges (HPDs), and neuronal and synaptic damage in the hippocampus during epilepsy. In addition, miconazole suppressed the KA-induced activation of the NF-κB pathway and iNOS production. Our results indicated miconazole to be an effective drug for disease-modifying effects during epilepsy, which may act by attenuating neuroinflammation through the suppression of NF-κB activation and iNOS production. At appropriate doses, miconazole may be a safe and effective approved drug that can easily be repositioned for clinical practice. [Display omitted] • Miconazole collectively elevated seizure threshold. • Miconazole suppressed neuroinflammation and attenuated the development of recurrent hippocampal paroxysm discharges. • Miconazole inhibited neuroinflammation through suppression of the NF-κB pathway and iNOS production. • Miconazole alleviated neuronal death and synaptic loss. [ABSTRACT FROM AUTHOR]