Fullerenol Nanoparticles Decrease Blood-Brain Barrier Interruption and Brain Edema during Cerebral Ischemia-Reperfusion Injury Probably by Reduction of Interleukin-6 and Matrix Metalloproteinase-9 Transcription

• Published in: Journal of stroke and cerebrovascular diseases 2018-11, Vol.27 (11), p.3053-3065
• Main Authors: Sarami Foroshani, Mahsa, Sobhani, Zeinab Sadat, Mohammadi, Mohammad Taghi, Aryafar, Masiha
• Format: Article
• Language: English
• Subjects: Blood-brain barrier; Fullerenol; Interleukin-6; Ischemic stroke; Matrix metalloproteinase-9
• ISSN: 1052-3057; 1532-8511
• DOI: 10.1016/j.jstrokecerebrovasdis.2018.06.042

The present study aimed to examine the protective role of fullerenol nanoparticles against blood-brain barrier (BBB) interruption and brain edema during cerebral ischemia-reperfusion injury probably by reduction of interleukin-6 (IL-6) and matrix metalloproteinase-9 (MMP-9) transcription. The male Wistar rats (weighting 280-320 g) were randomly assigned into four groups as follows: sham, control ischemic, pretreated ischemic, and posttreated ischemic groups. Cerebral ischemia-reperfusion (IR) injury was performed by occlusion of middle cerebral artery (MCA) for 90 minutes followed by twenty-four hours reperfusion. Rats were administered fullerenol 5mg/kg, intraperitoneally, 30 minutes before induction of IR in pretreated ischemic group and immediately after termination of MCA occlusion in posttreated ischemic group. After twenty-four hours reperfusion, the method of Evans blue dye extravasation (EBE) and RT-PCR were used for determination of BBB permeability and mRNA expression levels of MMP-9 and IL-6, respectively. Neuronal deficit score (NDS) and edema of the ischemic hemispheres were also evaluated. MCA occlusion increased NDS in control ischemic rats (3.16 ± 0.16) with concomitant increase in EBE (15.30 ± 3.98µg/g) and edema (3.53 ± 0.50%). Fullerenol in both pretreated and posttreated ischemic groups reduced NDS (36% and 68%, respectively), EBE (89% and 91%, respectively) and edema (53% and 81%, respectively). Although MCA occlusion increased the mRNA expression levels of MMP-9 and IL-6 in ischemic hemispheres, fullerenol in both treatment groups noticeably decreased the mRNA expression levels of these genes. In conclusion, fullerenol nanoparticles can protect BBB integrity and attenuate brain edema after cerebral ischemia-reperfusion injury possibly by reduction of IL-6 and MMP-9 transcription.