High-Mobility Group Box 1 Neutralization Prevents Chronic Cerebral Hypoperfusion-Induced Optic Tract Injuries in the Whi
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ORIGINAL RESEARCH
High‑Mobility Group Box 1 Neutralization Prevents Chronic Cerebral Hypoperfusion‑Induced Optic Tract Injuries in the White Matter Associated with Down‑regulation of Inflammatory Responses Yue Hei1 · Xin Zhang1 · Rong Chen2 · Yuefei Zhou1 · Dakuan Gao1 · Weiping Liu1 Received: 5 March 2019 / Accepted: 7 June 2019 © Springer Science+Business Media, LLC, part of Springer Nature 2019
Abstract Chronic cerebral hypoperfusion (CCH)-induced white matter lesions (WMLs) are region-specific with the optic tract (OT) displaying the most severe damages and leading to visual-based behavioral impairment. Previously we have demonstrated that anti-high-mobility group box 1 (HMGB1) neutralizing antibody (Ab) prevents CCH-induced hippocampal damages via inhibition of neuroinflammation. Here we tested the protective role of the Ab on CCH-induced OT injuries. Rats were treated with permanent occlusion of common carotid arteries (2-VO) or a sham surgery, and then administered with PBS, anti-HMGB1 Ab, or paired control Ab. Pupillary light reflex examination, visual water maze, and tapered beam-walking were performed 28 days post-surgery to investigate the behavioral deficits. Meanwhile, WMLs were measured by KlüverBarrera (KB) and H&E staining, and glial activation was further assessed to evaluate inflammatory responses in OT. Results revealed that anti-HMGB1 Ab ameliorated the morphological damages (grade scores, vacuoles, and thickness) in OT area and preserved visual abilities. Additionally, the increased levels of inflammatory responses and expressions of TLR4 and NF-κB p65 and phosphorylated NF-κB p65 (p-p65) in OT area were partly down-regulated after anti-HMGB1 treatment. Taken together, these findings suggested that HMGB1 neutralization could ease OT injuries and visual-guided behavioral deficits via suppressing inflammatory responses. Keywords HMGB1 neutralization · Chronic cerebral hypoperfusion · Optic tract · Glial activation · NF-κB
Introduction Chronic cerebral hypoperfusion (CCH) could cause longlasting reduction in cerebral blood flow (CBF) and result in white matter lesions (WMLs), visual dysfunction, glial activation, and cognitive impairments (Davidson et al. 2000; Farkas et al. 2007; Back et al. 2017). Permanent occlusion of common carotid arteries (2-VO) in rats has now been widely accepted as a suitable approach to unravel the pathological Yue Hei and Xin Zhang have contributed equally to this work. * Weiping Liu [email protected] 1
Department of Neurosurgery, Xijing Hospital, Fourth Military Medical University, No.17 Changle West Road, Xi’an 710032, People’s Republic of China
Department of Neurology, Xijing Hospital, Fourth Military Medical University, No.17 Changle West Road, Xi’an 710032, People’s Republic of China
2
changes and drug candidates for the treatment of WMLs in CCH and associated neurodegenerative diseases, such as vascular dementia (VaD), Alzheimer’s disease (AD), and aging (Farkas and Luiten 2001; Akinyemi et al. 2013). In particular, substantial evidence has shown th
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