Abstract
Cerebral infarction is a severe hypoxic ischemic necrosis with accelerated neuronal cell apoptosis in the brain. As a monoclonal antibody against interleukin 6, tocilizumab (TCZ) is widely used in immune diseases, whose function in cerebral infarction has not been studied. This study aims to reveal the role of TCZ in regulating neuronal cell apoptosis in cerebral infarction. The cerebral infarction rat model was constructed by middle cerebral artery occlusion and treated with TCZ. Cell apoptosis in hippocampus and cortex of the brain was examined with TUNEL method. Rat neuronal cells cultured in oxygen-glucose deprivation (OGD) conditions and treated with TCZ were used to compare cell viability and apoptosis. Apoptosis-related factors including B-cell lymphoma extra large (Bcl-xL) and Caspase 3, as well as the phosphorylated signal transducer and activator of transcription 3 (p-STAT3) in brain cortex were analyzed from the protein level. Results indicated that TCZ treatment could significantly prevent the promoted cell apoptosis caused by cerebral infarction or OGD (P < 0.05 or P < 0.01). In brain cortex of the rat model, TCZ up-regulated Bcl-xL and down-regulated Caspase 3, consistent with the inhibited cell apoptosis. It also promoted tyrosine 705 phosphorylation of STAT3, which might be the potential regulatory mechanism of TCZ in neuronal cells. This study provided evidence for the protective role of TCZ against neuronal cell apoptosis in cerebral infarction. Based on these fundamental data, TCZ is a promising option for treating cerebral infarction, but further investigations on related mechanisms are still necessary.
Highlights
Cerebral infarction is a severe hypoxic ischemic tissue necrosis in the brain, which is caused by blockage in brain vessels, including embolism and thrombosis
Accelerated neuronal cell apoptosis is an important manifestation of cerebral infarction [5,6], which is supposed to be induced by the modulation of apoptosis-related factors
interleukin 6 (IL-6) is up-regulated in the serum of acute cerebral infarction patients [10], having pivotal value in the diagnosis and treatment of cerebral infarction [11]
Summary
Cerebral infarction is a severe hypoxic ischemic tissue necrosis in the brain, which is caused by blockage in brain vessels, including embolism and thrombosis. Accelerated neuronal cell apoptosis is an important manifestation of cerebral infarction [5,6], which is supposed to be induced by the modulation of apoptosis-related factors, Submitted: 05 November 2015 / Accepted: 17 December 2015 such as the Caspase family and the B-cell lymphoma 2 (Bcl-2) family. IL-6 is up-regulated in the serum of acute cerebral infarction patients [10], having pivotal value in the diagnosis and treatment of cerebral infarction [11]. From this point of view, IL-6 and its agonists or antagonists are likely to play vital roles in the regulation of cerebral infarction
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