ABSTRACT
BACKGROUND AND PURPOSE: Inflammation and ferroptosis in astrocytes can be induced by external injuries, which results in excessive production of inflammatory factors and further injury on neurons. Alleviating ferroptosis might be an effective way to protect the brain from external injuries. The present study aims to explore the protective effects of Ferrostatin-1 against ferroptosis induced by Angiotensin II and the underlying mechanism. METHODS: The mouse primary astrocytes were isolated from the cortices of mice. The astrocytes were stimulated using 10 µM angiotensin II in the presence or absence of 1 or 2 µM Ferrostatin-1. The gene expression levels of AT1R, IL-6, IL-1ß, COX-2, GFAP, and GPx4 were evaluated using qRT-PCR. Western Blot was used to determine the protein levels of AT1R, COX-2, GFAP, GPx4, Nrf2, and HO-1 and ELISA was used to detect the concentrations of IL-6, IL-1ß, and PGE2. The ROS levels were evaluated using DHE staining and the reduced GSH level was determined using GSH detection kits. RESULTS: The expression levels of AT1R, IL-6, IL-1ß, COX-2, and GFAP in the astrocytes were significantly elevated by stimulation with Ang II and greatly suppressed by the introduction of Ferrostatin-1 in a dose-dependent manner. The promoted ROS level and inhibited GSH level in the astrocytes by the stimulation with Ang II were significantly reversed by Ferrostatin-1. Down-regulated GPx4, Nrf2, and HO-1 in the astrocytes induced by Ang II were extremely up-regulated by the treatment of Ferrostatin-1 in a dose-dependent manner. CONCLUSION: Ferrostatin-1 alleviates angiotensin II (Ang II)- induced inflammation and ferroptosis by suppressing the ROS levels and activating the Nrf2/HO-1 signaling pathway.
Subject(s)
Angiotensin II/toxicity , Anti-Inflammatory Agents/pharmacology , Antioxidants/pharmacology , Astrocytes/drug effects , Cerebral Cortex/drug effects , Cyclohexylamines/pharmacology , Ferroptosis/drug effects , Inflammation/prevention & control , Phenylenediamines/pharmacology , Animals , Astrocytes/metabolism , Astrocytes/pathology , Cells, Cultured , Cerebral Cortex/metabolism , Cerebral Cortex/pathology , Cytokines/metabolism , Heme Oxygenase-1/metabolism , Inflammation/metabolism , Inflammation/pathology , Inflammation Mediators/metabolism , Membrane Proteins/metabolism , Mice , NF-E2-Related Factor 2/metabolism , Oxidative Stress/drug effects , Reactive Oxygen Species/metabolism , Signal TransductionABSTRACT
Isolated bilateral cerebral peduncular infarctions (BCPI) presenting as acute pseudobulbar palsy are rarely reported and, to the best of our knowledge, most of the previous reports of BCPI were related to locked-in syndrome and disturbance of consciousness. Herein, we described a case of a 55-year-old man who presented with acute pseudobulbar palsy and mild tetraparesis, but preserved eye movements, with no consciousness disturbance. DWI revealed an acute infarction involving the central portion of the cerebral peduncle with a characteristic "traditional Chinese eight character" sign. The relationship between the infarcted range in the cerebral peduncle and the clinical manifestation was discussed in our report.
ABSTRACT
Wernekink commissure syndrome secondary to caudal paramedian midbrain infarction (CPMI) is a rare midbrain syndrome involving the decussation of the superior cerebellar peduncle in the caudal paramedian midbrain tegmentum. The central characteristics are constant bilateral cerebellar dysfunction, variable eye movement disorders, and rare delayed palatal myoclonus. Following is a description of the case of a 60-year-old man who presented with dizziness, slurred speech, and difficulty walking. Neurological examination revealed bilateral cerebellar dysfunction and bilateral internuclear ophthalmoplegia (bilateral INO). Serial magnetic resonance imaging (MRI) revealed a lesion in the caudal paramedian midbrain with a "heart-shaped" sign on fluid-attenuation inversion recovery images and a "V-shaped" appearance on diffusion-weighted imaging (DWI). An acute CPMI with a "heart or V" appearance sign was diagnosed. Upon follow-up evaluation 3 months later, a palatal tremor accompanied by involuntary head tremor was discovered. Hypertrophy and increased signal of the bilateral inferior olivary nucleus, compatible with hypertropic olivary degeneration (HOD) were revealed during a subsequent MRI study.
