Mifepristone alleviates cerebral ischemia-reperfusion injury in rats by stimulating PPAR γ. 2018

X-J Wu, and X-H Sun, and S-W Wang, and J-L Chen, and Y-H Bi, and D-X Jiang
Department of Neurology, Weihai Central Hospital of Shandong, Weihai, China. jdx_jiang163.com.

To investigate the changes of peroxisome proliferator-activated receptor gamma (PPAR γ) in focal cerebral ischemia-reperfusion injury, and to explore the effect and mechanism of mifepristone on the cerebral ischemia-reperfusion injury. Male Sprague-Dawley (SD) rats were selected, and the middle cerebral artery occlusion and reperfusion (MCAO/R) rat model was constructed using the longa's suture-occluded method. The sham operation group was not inserted with occlusion sutures. All experimental rats were divided into four groups: the sham operation group (SHA group), the MCAO/R model group (MCR group), the mifepristone intervention group (MIF group) (3 mg/kg, intragastric administration), and the mifepristone + bisphenol A diglycidyl ether (BADGE) intervention group (MIF+BAD group) [3 mg/kg mifepristone (intragastric administration) + 30 mg/kg BADGE (intraperitoneal injection)]. The long's scoring method (5 grades) was applied for scoring after reperfusion, at the time when the animals woke up, and at 48 h after awaking before execution, respectively. 48 h after the model was successfully established, triphenyl tetrazolium chloride (TTC) staining was performed to calculate the volume of cerebral infarction, and Nissl staining was conducted to observe the cranial nerve tissue morphology. Meanwhile, immune-histochemical staining was used to detect PPAR γ. Moreover, the protein expression levels of PPAR γ, tumor necrosis factor-alpha (TNF-α), interleukin-1 beta (IL-1β), interleukin-6 (IL-6), matrix metalloproteinase-2 (MMP-2), MMP-9 and tissue inhibitor of metalloproteinase 1 (TIMP-1) were examined by Western blotting (WB). Mifepristone could significantly enhance the neurological function after cerebral ischemia-reperfusion injury, reduce the volume of cerebral infarction, and improve the morphology of nerve tissues in rats. The expression of PPAR γ in the brain tissues of rats after cerebral ischemia-reperfusion injury markedly declined, whereas mifepristone could remarkably increase the protein expression of PPAR γ. After mifepristone intervention, the protein levels of TNF-α, IL-1β, IL-6, MMP-2, and MMP-9 in the infarcted brain tissues of rats were markedly decreased, while the expression of the TIMP-1 protein was increased. When combined with BADGE, the effect of mifepristone was partially offset. Mifepristone acts as a PPAR γ agonist, and relieves cerebral ischemia-reperfusion injury by restoring the balance between MMPs and TIMPs and inhibiting inflammatory cytokines.

UI MeSH Term Description Entries
D008297 Male Males
D009474 Neurons The basic cellular units of nervous tissue. Each neuron consists of a body, an axon, and dendrites. Their purpose is to receive, conduct, and transmit impulses in the NERVOUS SYSTEM. Nerve Cells,Cell, Nerve,Cells, Nerve,Nerve Cell,Neuron
D001921 Brain The part of CENTRAL NERVOUS SYSTEM that is contained within the skull (CRANIUM). Arising from the NEURAL TUBE, the embryonic brain is comprised of three major parts including PROSENCEPHALON (the forebrain); MESENCEPHALON (the midbrain); and RHOMBENCEPHALON (the hindbrain). The developed brain consists of CEREBRUM; CEREBELLUM; and other structures in the BRAIN STEM. Encephalon
D004195 Disease Models, Animal Naturally-occurring or experimentally-induced animal diseases with pathological processes analogous to human diseases. Animal Disease Model,Animal Disease Models,Disease Model, Animal
D000818 Animals Unicellular or multicellular, heterotrophic organisms, that have sensation and the power of voluntary movement. Under the older five kingdom paradigm, Animalia was one of the kingdoms. Under the modern three domain model, Animalia represents one of the many groups in the domain EUKARYOTA. Animal,Metazoa,Animalia
D015398 Signal Transduction The intracellular transfer of information (biological activation/inhibition) through a signal pathway. In each signal transduction system, an activation/inhibition signal from a biologically active molecule (hormone, neurotransmitter) is mediated via the coupling of a receptor/enzyme to a second messenger system or to an ion channel. Signal transduction plays an important role in activating cellular functions, cell differentiation, and cell proliferation. Examples of signal transduction systems are the GAMMA-AMINOBUTYRIC ACID-postsynaptic receptor-calcium ion channel system, the receptor-mediated T-cell activation pathway, and the receptor-mediated activation of phospholipases. Those coupled to membrane depolarization or intracellular release of calcium include the receptor-mediated activation of cytotoxic functions in granulocytes and the synaptic potentiation of protein kinase activation. Some signal transduction pathways may be part of larger signal transduction pathways; for example, protein kinase activation is part of the platelet activation signal pathway. Cell Signaling,Receptor-Mediated Signal Transduction,Signal Pathways,Receptor Mediated Signal Transduction,Signal Transduction Pathways,Signal Transduction Systems,Pathway, Signal,Pathway, Signal Transduction,Pathways, Signal,Pathways, Signal Transduction,Receptor-Mediated Signal Transductions,Signal Pathway,Signal Transduction Pathway,Signal Transduction System,Signal Transduction, Receptor-Mediated,Signal Transductions,Signal Transductions, Receptor-Mediated,System, Signal Transduction,Systems, Signal Transduction,Transduction, Signal,Transductions, Signal
D015427 Reperfusion Injury Adverse functional, metabolic, or structural changes in tissues that result from the restoration of blood flow to the tissue (REPERFUSION) following ISCHEMIA. Ischemia-Reperfusion Injury,Injury, Ischemia-Reperfusion,Injury, Reperfusion,Reperfusion Damage,Damage, Reperfusion,Injury, Ischemia Reperfusion,Ischemia Reperfusion Injury,Ischemia-Reperfusion Injuries,Reperfusion Damages,Reperfusion Injuries
D015735 Mifepristone A progestational and glucocorticoid hormone antagonist. Its inhibition of progesterone induces bleeding during the luteal phase and in early pregnancy by releasing endogenous prostaglandins from the endometrium or decidua. As a glucocorticoid receptor antagonist, the drug has been used to treat hypercortisolism in patients with nonpituitary CUSHING SYNDROME. Mifegyne,Mifeprex,Mifégyne,R-38486,R38486,RU-38486,RU-486,ZK-98296,ZK98296,R 38486,RU 38486,RU 486,RU38486,RU486,ZK 98296
D016207 Cytokines Non-antibody proteins secreted by inflammatory leukocytes and some non-leukocytic cells, that act as intercellular mediators. They differ from classical hormones in that they are produced by a number of tissue or cell types rather than by specialized glands. They generally act locally in a paracrine or autocrine rather than endocrine manner. Cytokine
D017207 Rats, Sprague-Dawley A strain of albino rat used widely for experimental purposes because of its calmness and ease of handling. It was developed by the Sprague-Dawley Animal Company. Holtzman Rat,Rats, Holtzman,Sprague-Dawley Rat,Rats, Sprague Dawley,Holtzman Rats,Rat, Holtzman,Rat, Sprague-Dawley,Sprague Dawley Rat,Sprague Dawley Rats,Sprague-Dawley Rats

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