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      Hyperbaric Oxygen Treatment Improves Intestinal Barrier Function After Spinal Cord Injury in Rats

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          Abstract

          Intestinal barrier dysfunction is often observed clinically after spinal cord injury (SCI) and seriously affects long-term quality of life. Hyperbaric oxygen (HBO) treatment has been proved to promote barrier function recovery after injury, but the influence of HBO on intestinal barrier function following SCI is unclear. We aimed to investigate the effect and mechanisms of HBO treatment on intestinal barrier function by measuring the level of tight junction (TJ) proteins and the Ras homolog (Rho)/Rho-associated coiled-coil forming protein kinase (ROCK) signaling pathway. SCI model was established in rats, and the animals were randomly assigned into three groups: sham-operation group (SH), SCI group and SCI+HBO group. In the SCI+HBO group, the rats inhaled 100% O 2 for 1 h at 2.0 atmospheres absolute pressure (ATA) once per day after surgery. Neurological function and intestinal permeability were assessed after surgery, and the jejunum tissue was excised for histological and intestinal barrier function evaluations. The protein levels of TJ and the Rho/ROCK signaling pathway were also measured. The results showed that in the SCI group, intestinal mucosal injury score, intestinal permeability, and levels of Rho and ROCK1 were higher, and TJ proteins occludin and ZO-1 were lower than those in the SH group ( P < 0.01). HBO treatment significantly inhibited the expression of Rho and ROCK1, increased occludin and ZO-1 expression, decreased intestinal permeability, and alleviated intestinal mucosal injury as compared with the SCI group ( P < 0.05, P < 0.01). The SCI+HBO group showed higher Basso–Beattie–Bresnahan (BBB) scores relative to the SCI group on postoperative days 7 and 14 ( P < 0.01). There was a significant negative correlation between BBB score and intestinal mucosal injury score in rats after HBO treatment ( P < 0.05). We concluded from this study that HBO treatment promoted the expression of TJ proteins possibly through inhibiting Rho/ROCK signaling pathway, which protected the intestinal barrier function and improved the intestinal permeability after SCI in rats.

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          Most cited references38

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          Graded histological and locomotor outcomes after spinal cord contusion using the NYU weight-drop device versus transection.

          Injury reproducibility is an important characteristic of experimental models of spinal cord injuries (SCI) because it limits the variability in locomotor and anatomical outcome measures. Recently, a more sensitive locomotor rating scale, the Basso, Beattie, and Bresnahan scale (BBB), was developed but had not been tested on rats with severe SCI complete transection. Rats had a 10-g rod dropped from heights of 6.25, 12.5, 25, and 50 mm onto the exposed cord at Tl 0 using the NYU device. A subset of rats with 25 and 50 mm SCI had subsequent spinal cord transection (SCI + TX) and were compared to rats with transection only (TX) in order to ascertain the dependence of recovery on descending systems. After 7-9 weeks of locomotor testing, the percentage of white matter measured from myelin-stained cross sections through the lesion center was significantly different between all the groups with the exception of 12.5 vs 25 mm and 25 vs 50 mm groups. Locomotor recovery was greatest for the 6.25-mm group and least for the 50-mm group and was correlated positively to the amount of tissue sparing at the lesion center (p 0.05). Thus, spared descending systems appear to modify segmental systems which produce greater behavioral improvements than isolated cord systems.
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            Gut dysbiosis impairs recovery after spinal cord injury

            Kigerl et al. show that spinal cord injury causes profound changes in gut microbiota and that these changes in gut ecology are associated with activation of GALT immune cells. They show that feeding mice probiotics after SCI confers neuroprotection and improves functional recovery.
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              Rho-kinase: regulation, (dys)function, and inhibition.

              In a variety of normal and pathological cell types, Rho-kinases I and II (ROCKI/II) play a pivotal role in the organization of the nonmuscle and smooth muscle cytoskeleton and adhesion plaques as well as in the regulation of transcription factors. Thus, ROCKI/II activity regulates cellular contraction, motility, morphology, polarity, cell division, and gene expression. Emerging evidence suggests that dysregulation of the Rho-ROCK pathways at different stages is linked to cardiovascular, metabolic, and neurodegenerative diseases as well as cancer. This review focuses on the current status of understanding the multiple functions of Rho-ROCK signaling pathways and various modes of regulation of Rho-ROCK activity, thereby orchestrating a concerted functional response.
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                Author and article information

                Contributors
                Journal
                Front Neurol
                Front Neurol
                Front. Neurol.
                Frontiers in Neurology
                Frontiers Media S.A.
                1664-2295
                15 October 2020
                2020
                : 11
                : 563281
                Affiliations
                [1] 1Department of Hyperbaric Oxygen Medicine, Beijing Chaoyang Hospital, Capital Medical University , Beijing, China
                [2] 2Department of Orthopedic Surgery, Beijing Chaoyang Hospital, Capital Medical University , Beijing, China
                Author notes

                Edited by: Hua Feng, Army Medical University, China

                Reviewed by: Jason H. Huang, Baylor Scott and White Health, United States; Günalp Uzun, Gülhane Askerî Tip Akademisi, Turkey

                *Correspondence: Jing Yang yangjinghbo@ 123456ccmu.edu.cn

                This article was submitted to Neurotrauma, a section of the journal Frontiers in Neurology

                Article
                10.3389/fneur.2020.563281
                7593681
                33178107
                cc2a8bad-5da0-4ec4-91b9-472c51957ac6
                Copyright © 2020 Liu, Liang, Zhang, Li, Yang and Kang.

                This is an open-access article distributed under the terms of the Creative Commons Attribution License (CC BY). The use, distribution or reproduction in other forums is permitted, provided the original author(s) and the copyright owner(s) are credited and that the original publication in this journal is cited, in accordance with accepted academic practice. No use, distribution or reproduction is permitted which does not comply with these terms.

                History
                : 18 May 2020
                : 31 August 2020
                Page count
                Figures: 9, Tables: 0, Equations: 0, References: 38, Pages: 12, Words: 6227
                Funding
                Funded by: Beijing Municipal Natural Science Foundation 10.13039/501100005089
                Categories
                Neurology
                Original Research

                Neurology
                hyperbaric oxygen,intestinal barrier,spinal cord injury,tight junction protein,rho/rock signaling pathway

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