Effect of combined chondroitinase ABC and hyperbaric oxygen therapy in a rat model of spinal cord injury

Abstract

The present study aimed to investigate the effect of combined hyperbaric oxygen (HBO) and chondroitinase ABC (ChABC) enzyme therapy in a rat model of spinal cord injury (SCI) and to explore the underlying mechanisms. A total of 48 healthy male Wistar rats were randomly divided into six groups: Sham, SCI, vehicle, HBO, ChABC enzyme and HBO + ChABC. Excluding the sham group, SCI was established in rats by a clip compression injury and rats subsequently received HBO treatment for 2 weeks with or without an intraspinal injection of 0.1 U/µl ChABC. Neuromotor functions were examined using the Basso-Beattie-Bresnahan locomotor rating scale and the inclined plane assessment at baseline and for 4 weeks following SCI establishment. Superoxide dismutase (SOD) and malondialdehyde (MDA) levels were also measured, in addition to the expression of glycogen synthase kinase-3β (GSK3β) and aquaporin 4 (AQP4). Results revealed that combined HBO and ChABC treatment significantly improved neuromotor function compared with the HBO or ChABC treatments alone. HBO and/or ChABC treatment significantly increased SOD and decreased MDA levels, as well as GSK3β expression, compared with the sham and SCI rats. The combined HBO and ChABC treatment significantly inhibited SCI-induced AQP4 expression, but ChABC alone did not. Functional recovery in the HBO + ChABC group was significantly increased compared with the HBO or ChABC groups. These results indicate that combined HBO and ChABC treatment is more effective in treating SCI than either therapy alone.

Chondroitinase ABC Administration in Locomotion Recovery After Spinal Cord Injury: A Systematic Review and Meta-analysis

“…The search resulted in 1,096 non-duplicate articles. After studying the titles and abstracts of these articles, 136 articles were regarded as potentially eligible to enter this review, and finally, 34 articles were included ( Bai et al, 2010 ; Bradbury et al, 2002 ; Caggiano et al, 2005 ; Cheng et al, 2015 ; Führmann et al, 2018 ; García-Alías et al, 2009 ; García-Alías et al, 2008 ; García-Alías et al, 2011 ; Grosso et al, 2014 ; Huang et al, 2006 ; Ishikawa et al, 2015 ; Janzadeh et al, 2017 ; Karimi-Abdolrezaee et al, 2010 ; Kim et al, 2006 ; Lee et al, 2012 ; Liu, et al, 2018 ; Mountney et al, 2013 ; Ni et al, 2015 ; Novotna et al, 2018; Raspa, Bolla et al, 2019 ; Sarveazad et al, 2017 ; Sarveazad et al, 2014 ; Shinozaki et al, 2016 ; Takeuchi et al, 2013 ; Tom et al, 2009 ; Wang et al, 2011a ; Wang et al, 2011b ; Xia et al, 2017 ; Xia et al, 2015 ; Xiong et al, 2016 ; Yang et al, 2009 ; Yoo et al, 2013 ; Zhao et al, 2013 ) ( Figure 1 ). These 34 studies contained 44 separate experiments evaluating several different protocols, including variations in the SCI severity, the prescription method, the prescription dose, and the interval time between SCI and ChABC administration.…”

Perspectives in the Cell-Based Therapies of Various Aspects of the Spinal Cord Injury-Associated Pathologies: Lessons from the Animal Models

“…Furthermore, iPSCs-derived neurospheres [ 105 ], MSCs-derived exosomes, or an MSC-conditioned medium were shown to secrete proangiogenic factors such as VEGF, FGF2, and angiogenin. This effect was observed both in vitro and in vivo, where the newly formed vessels were found in rat injured spinal cords after treatment with MSC exosomes [ 106 , 107 ].…”

“…The enzymatic approach produces particularly good results in combination with other procedures, such as simultaneous peripheral nerve transplantation [ 119 ], hyperbaric oxygen therapy [ 107 ], laser irradiation [ 120 ], or transplantation of different type of exogenous cells [ 121 , 122 ] or treadmill training [ 123 ]. An approach of intrathecal pretreatment with chondroitinase ABC before the transplantation of induced pluripotent stem cell-derived neural stem cells (iPS-NSCs) in mice subjected to spinal cord injury contributed to glial scar reduction [ 122 ].…”

Rational design of a nitroreductase-activatable two-photon fluorescent probe for hypoxia imaging in cell and in vivo

“…The mice in HBO-assistant chemotherapy group were exposed to 80 % oxygen every day (five times per week) for 60 min and given G/ C biweekly for 28 days (Fig. 5 details seen SI) [32,44,49,50]. Then the NTR concentrations were detected using TP-NO 2 , and the fluorescence signal acquisition was continued for 30 min.…”