scholarly journals Pioglitazone Confers Neuroprotection Against Ischemia-Induced Pyroptosis due to its Inhibitory Effects on HMGB-1/RAGE and Rac1/ROS Pathway by Activating PPAR-ɤ

2018 ◽  
Vol 45 (6) ◽  
pp. 2351-2368 ◽  
Author(s):  
Pingping Xia ◽  
Yundan Pan ◽  
Fan Zhang ◽  
Na Wang ◽  
E Wang ◽  
...  
Keyword(s):  
Middle Cerebral Artery ◽  
Artery Occlusion ◽  
Protective Effects ◽  
Inhibitory Effects ◽  
Ppar Γ ◽  
Rac1 Activity ◽  
Cultured Astrocytes ◽  
Cerebral Artery Occlusion ◽  
Rage Expression ◽  
Primary Cultured Astrocytes

Background/Aims: Recent researches highlighted the protective potential of pioglitazone, a PPAR-γ agonist, in the progression of cerebral ischemia-reperfusion injury. However, there has been no study on the application of pioglitazone in treating ischemic stroke through mechanisms involving pyroptosis. Methods: The cerebral injury was established by middle cerebral artery occlusion (MCAO). in vitro ischemia in primary cultured astrocytes was induced by the oxygen-glucose deprivation (OGD). ELISA and Western Blot analysis were employed to the levels of PPAR-γ, pyroptosis-related biomarkers and cytoplasmic translocation of HMGB-1 and RAGE expression as well as Rac1 activity, respectively. Results: We demonstrated that repeated intraperitoneal administration of pioglitazone remarkably reduced the infarct volume, improved neurological deficits and suppressed the Rac1 activity with significant reduction of excessive ROS in rat model of middle cerebral artery occlusion (MCAO). Moreover, pioglitazone alleviated the up-regulation of pyroptosis-related biomarkers and the increased cytoplasmic translocation of HMGB-1 and RAGE expression in cerebral penumbra cortex. Similarly, the protective effects of pioglitazone on cultured astrocytes were characterized by reduced Rac1 activity, pyroptosis related protein expressions and lactate dehydrogenase (LDH) release. However, these protective effects of pioglitazone were neutralized with the use of GW9662, a PPAR-γ inhibitor. Interestingly, Rac1 knockdown in lentivirus with the Rac1 small hair RNA (shRNA) could inhibit the OGD-induced pyroptosis of primary cultured astrocytes. Furthermore, the combination of Rac1-shRNA and pioglitazone can further strengthen the inhibitory effects on pyroptosis induced by OGD. Conclusion: The neuroprotection of pioglitazone was attributable to the alleviated ischemia/hypoxia-induced pyroptosis and was also associated with the PPARγ-mediated suppression of HGMB-1/RAGE signaling pathway. Moreover, the inhibition of Rac1 promoted this function.

Water-soluble fullerene derivatives (C60(OH)18-22) decrease infarct volume and edema after middle cerebral artery occlusion in rat

2016 ◽  
Vol 2 (1) ◽  
pp. 80-89
Author(s):  
Masiha Aryafar ◽  
Mohammad Taghi Mohammadi ◽  
Zeinab Sadat Sobhani ◽  
Mahsa Sarami Foroshani ◽  
Javad Rasouli Vani
Keyword(s):  
Middle Cerebral Artery ◽  
Middle Cerebral Artery Occlusion ◽  
Cerebral Artery ◽  
Infarct Volume ◽  
Artery Occlusion ◽  
Water Soluble ◽  
Protective Effects ◽  
Fullerene Derivatives ◽  
Reperfusion Period ◽  
Cerebral Artery Occlusion

Overproduction of oxygen free radicals (ROS) and oxidative stress during reperfusion period plays a critical role in pathophysiology of cerebral ischemia-reperfusion injury. Since the antioxidant properties of fullerene nanoparticles has been extensively demonstrated, we assessed the possible protective effects of water-soluble fullerene derivatives (C60(OH)18-22) on infarct volume and edema after middle cerebral artery occlusion in rat.Twenty four rats were randomly divided into three groups (each group; n=8): sham, control ischemia (IR) and ischemic treatment groups. Cerebral ischemia was induced by 90 min middle cerebral artery occlusion (MCAO) followed by 24 hours reperfusion. Fullerene nanoparticles were given orally at dose of 1mg/kg immediately after termination of MCAO and the beginning of reperfusion period. The brains were processed for histopathological assessment and quantitation of the infarct volume (TTC staining method). Finally, the brain hemispheres were weighed as an index of brain edema.There was no infarction and edema in right hemispheres of sham rats. MCAO induced brain infarction both in cortex (261±23mm3) and subcortex (138±23mm3) and also right hemispheres weights (23%) of control ischemic rats. Administration of fullerene reduced the infarction both in cortex (49±26mm3) and subcortex (43±21mm3) and also the value of right hemisphere weight (20%) of ischemic treatment rats. Additionally in histopathological assessment, the perivascular areas decreased in ischemic treatment rats.The findings of present study are revealing the protective effects of water-soluble fullerene derivatives against reperfusion-induced injury such as infarction and edema after middle cerebral artery occlusion in rat.

Chitosan-coated C-phycocyanin Liposome for Extending the Neuroprotective Time Window Against Ischemic Brain Stroke

2018 ◽  
Vol 24 (17) ◽  
pp. 1859-1864 ◽  
Author(s):  
Goo Yong Chung ◽  
Kyou Hee Shim ◽  
Hye Jin Kim ◽  
Seul Ki Min ◽  
Hwa Sung Shin
Keyword(s):  
Middle Cerebral Artery ◽  
Middle Cerebral Artery Occlusion ◽  
Inflammatory Cytokines ◽  
Time Window ◽  
Artery Occlusion ◽  
Ischemic Brain ◽  
Chitosan Coating ◽  
Cultured Astrocytes ◽  
Brain Stroke ◽  
Cerebral Artery Occlusion

The time window for neuroprotection during ischemic brain stroke is short, and hence, development of neuroprotectants is critical to extend this time window. This study sought to verify if muco-adhesive chitosan coating improves the neuroprotective potential of the pre-proven C-Phycocyanin-pertaining liposome (C-Pc liposome). The use of chitosan-coated liposomes extended the neuroprotective time window by 6 h after occlusion, and further improved the neuroprotection efficiency of the C-Pc liposome in a rat Middle Cerebral Artery Occlusion (MCAO) model. Beneficial changes in mRNA expressions of antioxidants, inflammatory cytokines and glia scar proteoglycans were evident in the C-Pc liposomes. In addition, in the cultured astrocytes, the chitosan- coated C-Pc liposome expressed anti-oxidative activity without cytotoxicity.

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