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Fullerene nanoparticle as a therapeutic agent for protection of neurovascular unit in cerebral ischemia-reperfusion injuries
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Mohammad Taghi Mohammadi   , Mahsa Sarami Foroshani , Zeinab Sadat Sobhani , Masiha Aryafar , Shamsi Darabi , Javad Rasoli Vani |
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Abstract: (300 Views) |
Introduction: Fullerene (C60), the third spherical allotrope of carbon, can remove various free radicals in the biological milieus more efficiently than cellular antioxidants. We conducted a study to determine the effectiveness of polyhydroxylated fullerenes (C60 (OH) 18-22), also known as fullerenol, in protecting the brain from injury caused by cerebral ischemia-reperfusion (IR) during an experimental model of ischemic stroke.
Methods and Materials: We randomly assigned Male Wistar rats into sham, control ischemic, pre-treated ischemic, and post-treated ischemic groups. Cerebral IR injury was induced by occlusion of the middle cerebral artery (MCA) for 90 minutes followed by 24-hour reperfusion. Rats were administered fullerenol 5mg/kg, intraperitoneally, 30min before induction of IR in the pre-treated ischemic group and immediately after termination of MCA occlusion in the post-treated ischemic group. Brain infarction and edema, blood-brain-barrier (BBB) permeability, and mRNA expression levels of MMP-9, IL-6, γ-glutamyl transpeptidase (GGT), P53, and aquaporin-1 as well as oxidative stress markers were determined after the termination of reperfusion phase.
Results: Based on our research, it was discovered that fullerenol reduced brain infarction caused by ischemia in rats. Additionally, it reduced the amount of oxidative damage to the brain affected by ischemia and boosted the antioxidant system of the affected brain by increasing the activity of antioxidant enzymes. Fullerenol decreased GGT and P53 and aquaporin-1 expression in the ischemic areas in cerebral IR injuries. Using fullerenol nanoparticles during cerebral IR was found to attenuate the ischemia-induced brain edema and also protect the integrity of BBB against brain IR injuries through inhibition of MMP-9 and IL-6 expression.
Conclusions: Fullerenol nanoparticles can decrease brain infarction and edema as well as BBB disruption by protecting brain microvasculature and BBB integrity during IR injuries. Based on our findings, we recommend using this nanoparticle for therapeutic purposes to decrease cerebral IR injuries following an ischemic stroke.
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| Keywords: Ischemic stroke, Blood-brain barrier, inflammation, oxidative stress, Fullerenol |
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Full-Text [PDF 330 kb]
(42 Downloads)
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Type of Study: Research |
Subject:
General
Received: 2023/11/23 | Accepted: 2023/08/23 | Published: 2023/08/23
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