cytochrome-c-t and interleukin-1beta-(163-171)

NADPH oxidase is a major complex that produces reactive oxygen species (ROSs) during the ischemic period and aggravates brain damage and cell death after ischemic injury. Although many approaches have been tested for preventing production of ROSs by NADPH oxidase in ischemic brain injury, the regulatory mechanisms of NADPH oxidase activity after cerebral ischemia are still unclear. The aim of this study is identifying apocynin as a critical modulator of NADPH oxidase and elucidating its role as a neuroprotectant in an experimental model of brain ischemia in rat. Treatment of apocynin 5min before of reperfusion attenuated cerebral ischemia in rats. Administration of apocynin showed marked reduction in infarct size compared with that of control rats. Medial carotid artery occlusion (MCAo)-induced cerebral ischemia was also associated with an increase in, nitrotyrosine formation, as well as IL-1β expression, IκB degradation and ICAM expression in ischemic regions. These expressions were markedly inhibited by the treatment of apocynin. We also demonstrated that apocynin reduces levels of apoptosis (TUNEL, Bax and Bcl-2 expression) resulting in a reduction in the infarct volume in ischemia-reperfusion brain injury. This new understanding of apocynin induced adaptation to ischemic stress and inflammation could suggest novel avenues for clinical intervention during ischemic and inflammatory diseases.

Topics: Acetophenones; Animals; Apoptosis; bcl-2-Associated X Protein; Brain; Cytochromes c; Disease Models, Animal; Enzyme Inhibitors; Gene Expression Regulation, Enzymologic; I-kappa B Proteins; In Situ Nick-End Labeling; Infarction, Middle Cerebral Artery; Intercellular Adhesion Molecule-1; Interleukin-1beta; Male; NADPH Oxidases; Neurologic Examination; Peptide Fragments; Proto-Oncogene Proteins c-bcl-2; Rats; Rats, Wistar; Reperfusion Injury; Tyrosine

Nerve growth factor (NGF) undergoes significant changes in the central nervous system (CNS) of patients affected by multiple sclerosis (MS) and of rats with experimental allergic encephalomyelitis (EAE). The major histocompatibility complex (MCH) class I and class II antigens are molecules that play a pivotal role in these neuro-inflammatory disorders. The aim of this study was to investigate the role of NGF on MCH class I and class II antigens in spinal cords cells of EAE rats. It was found that the administration of NGF in EAE rats enhances MHC-I, IFN-gamma receptor and interferon regulatory factor-1 expression on the neurons but not in the glial cells, while NGF decreased MHC class II antigen in the glial cells. NGF administration into the brain of EAE rats has no effect on TNF-alpha expression. The present findings suggest that NGF may have a regulatory function in spinal cord cells during tissue inflammation.

Topics: Analysis of Variance; Animals; Blotting, Western; Cell Count; Cytochromes c; Disease Models, Animal; Encephalomyelitis, Autoimmune, Experimental; Enzyme-Linked Immunosorbent Assay; Female; Gene Expression Regulation; Histocompatibility Antigens Class I; Histocompatibility Antigens Class II; Immunohistochemistry; Interferon gamma Receptor; Interferon Regulatory Factor-1; Interleukin-1; Interleukin-10; Interleukin-1beta; Nerve Growth Factor; Neurons; Peptide Fragments; Rats; Rats, Inbred Lew; Receptors, Interferon; Spinal Cord