Maresin 1 improves cognitive decline and ameliorates inflammation and blood-brain barrier damage in rats with chronic cerebral hypoperfusion

• Published in: Brain research 2022-08, Vol.1788, p.147936-147936, Article 147936
• Main Authors: Li, Tian, Zheng, Jiaxin, Wang, Zhitian, Xu, Lingling, Sun, Dong, Song, Hao, Wu, Shenjia, Du, Miaoyu, Peng, Sisi, Zhang, Junjian
• Format: Article
• Language: English
• Subjects: Animals; Blood brain barrier; Blood-Brain Barrier - metabolism; Brain Ischemia - complications; Brain Ischemia - pathology; Chronic cerebral hypoperfusion; Claudin-5 - metabolism; Cognitive Dysfunction - etiology; Cognitive Dysfunction - metabolism; Cognitive impairment; Docosahexaenoic Acids; Inflammation; Maresin1; Matrix Metalloproteinase 9 - metabolism; NF-kappa B - metabolism; Rats; Rats, Sprague-Dawley; Tumor Necrosis Factor-alpha - metabolism
• ISSN: 0006-8993; 1872-6240
• DOI: 10.1016/j.brainres.2022.147936

[Display omitted] •Maresin1 (MaR1) can improve cognitive impairment in chronic cerebral hypoperfusion (CCH) rats.•MaR1 can ameliorate neuroinflammation caused by CCH.•MaR1 can attenuate hippocampal blood–brain barrier (BBB) damage of CCH rats, which may improve cognition in CCH rats by MaR1. Chronic inflammation and blood–brain barrier destruction are interrelated pathological changes in chronic cerebral hypoperfusion (CCH) that promote vascular cognitive impairment (VCI). Therefore, we discussed the impact of the macrophage mediator in resolving inflammation 1 (Maresin 1) on the CCH-induced cognitive impairment and its underlying mechanisms. 66 rats were randomly divided into three groups: Sham (n = 22), 2VO (n = 22), and 2VO + MaR1 (n = 22). Rats in three groups received 2-Vessel Occlusion (2VO) or sham operation and received intrathecal delivery of PBS or MaR1. Hippocampal blood flow and Modified neurological severity scores (mNSS) were used to confirm models’ effect. Blood-brain barrier (BBB) damage was assessed by Evans blue (EB) leakage experiments and spectrophotometry, the BBB ultrastructure was observed with a transmission electron microscope (TEM), and the expression of zonula occluden-1 (ZO-1), claudin-5, and matrix metalloproteinases-9 (MMP-9) were detected with Enzyme-Linked Immunosorbent Assay (ELISA). Morris water maze (MWM) was used to assess cognitive function. Tumor necrosis factor (TNF-α), interleukin-1β (IL-1β), and nuclear factor-κB (NF-κB) expression were examined by Western blotting (WB) and ELISA. Immunofluorescence was used to detect microglia, astrocytes and oligodendrocytes. Rats developed obvious cognitive impairment by CCH. BBB showed EB leakage, ultrastructural destruction, degradation of ZO-1, Claudin-5, and up-regulation of MMP-9. Inactivation of oligodendrocytes, activation of microglia and astrocyte and increased expression of NF-κB, TNF-α, and IL-1β has been detected. MaR1 administration significantly reverted these changes. MaR1 can improve the CCH-induced cognitive impairment. Inflammatory resolution and BBB protection may be the mechanism of MaR1 to prevent CCH-induced cognitive impairment.