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

Liu,Xiaoyang; Wang,Jiefeng; Li,Guangkuo; Lv,Honglin

doi:10.3892/mmr.2018.8933

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

Authors:
- Xiaoyang Liu
- Jiefeng Wang
- Guangkuo Li
- Honglin Lv
View Affiliations

Affiliations: Department of Spine Surgery, Yantai Yuhuangding Hospital, Yantai, Shandong 264000, P.R. China
Published online on: April 26, 2018 https://doi.org/10.3892/mmr.2018.8933
Pages: 25-30
Copyright: © Liu et al. This is an open access article distributed under the terms of Creative Commons Attribution License.

Metrics: Total Views: 0 (Spandidos Publications: | PMC Statistics: )

Metrics: Total PDF Downloads: 0 (Spandidos Publications: | PMC Statistics: )

Cited By (CrossRef): 0 citations Loading Articles...

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.

View Figures

View References

1	Jackson A: Spinal-cord injury: Neural interfaces take another step forward. Nature. 539:177–178. 2016. View Article : Google Scholar : PubMed/NCBI
2	Ropper AE and Ropper AH: Acute spinal cord compression. N Engl J Med. 376:1358–1369. 2017. View Article : Google Scholar : PubMed/NCBI
3	Hall ED: Lipid antioxidants in acute central nervous system injury. Ann Emerg Med. 22:1022–1027. 1993. View Article : Google Scholar : PubMed/NCBI
4	Ajiboye AB, Willett FR, Young DR, Memberg WD, Murphy BA, Miller JP, Walter BL, Sweet JA, Hoyen HA, Keith MW, et al: Restoration of reaching and grasping movements through brain-controlled muscle stimulation in a person with tetraplegia: A proof-of-concept demonstration. Lancet. 389:1821–1830. 2017. View Article : Google Scholar : PubMed/NCBI
5	Capogrosso M, Milekovic T, Borton D, Wagner F, Moraud EM, Mignardot JB, Buse N, Gandar J, Barraud Q, Xing D, et al: A brain-spine interface alleviating gait deficits after spinal cord injury in primates. Nature. 539:284–288. 2016. View Article : Google Scholar : PubMed/NCBI
6	Lebedev MA and Nicolelis MA: Brain-machine interfaces: From basic science to neuroprostheses and neurorehabilitation. Physiol Rev. 97:767–837. 2017. View Article : Google Scholar : PubMed/NCBI
7	Bagherzadeh K, Maleki M, Golestani A, Khajeh K and Amanlou M: Chondrotinase ABC I thermal stability is enhanced by site-directed mutagenesis: A molecular dynamic simulations approach. J Biomol Struct Dyn. 1–10. 2017.
8	Rauvala H, Paveliev M, Kuja-Panula J and Kulesskaya N: Inhibition and enhancement of neural regeneration by chondroitin sulfate proteoglycans. Neural Regen Res. 12:687–691. 2017. View Article : Google Scholar : PubMed/NCBI
9	Yuan YM and He C: The glial scar in spinal cord injury and repair. Neurosci Bull. 29:421–435. 2013. View Article : Google Scholar : PubMed/NCBI
10	Muramoto A, Imagama S, Natori T, Wakao N, Ando K, Tauchi R, Hirano K, Shinjo R, Matsumoto T, Ishiguro N and Kadomatsu K: Midkine overcomes neurite outgrowth inhibition of chondroitin sulfate proteoglycan without glial activation and promotes functional recovery after spinal cord injury. Neurosci Lett. 550:150–155. 2013. View Article : Google Scholar : PubMed/NCBI
11	Jones LL, Margolis RU and Tuszynski MH: The chondroitin sulfate proteoglycans neurocan, brevican, phosphacan, and versican are differentially regulated following spinal cord injury. Exp Neurol. 182:399–411. 2003. View Article : Google Scholar : PubMed/NCBI
12	Dill J, Wang H, Zhou F and Li S: Inactivation of glycogen synthase kinase 3 promotes axonal growth and recovery in the CNS. J Neurosci. 28:8914–8928. 2008. View Article : Google Scholar : PubMed/NCBI
13	Akbari M, Khaksari M, Rezaeezadeh-Roukerd M, Mirzaee M and Nazari-Robati M: Effect of chondroitinase ABC on inflammatory and oxidative response following spinal cord injury. Iran J Basic Med Sci. 20:806–812. 2017.PubMed/NCBI
14	Cheng CH, Lin CT, Lee MJ, Tsai MJ, Huang WH, Huang MC, Lin YL, Chen CJ, Huang WC and Cheng H: Local delivery of high-dose chondroitinase ABC in the sub-acute stage promotes axonal outgrowth and functional recovery after complete spinal cord transection. PLoS One. 10:e01387052015. View Article : Google Scholar : PubMed/NCBI
15	Graham JB and Muir D: Chondroitinase C selectively degrades chondroitin sulfate glycosaminoglycans that inhibit axonal growth within the endoneurium of peripheral nerve. PLoS One. 11:e01676822016. View Article : Google Scholar : PubMed/NCBI
16	Wang IC, Liu HT, Yu CM, Whu SW, Lin SS, Su CI, Chen CH and Chen WJ: Effect of hyperbaric oxygenation on intervertebral disc degeneration: An in vivo study with sprague-dawley rats. Spine (Phila Pa 1976). 38:E137–E142. 2013. View Article : Google Scholar : PubMed/NCBI
17	Alluin O, Delivet-Mongrain H, Gauthier MK, Fehlings MG, Rossignol S and Karimi-Abdolrezaee S: Examination of the combined effects of chondroitinase ABC, growth factors and locomotor training following compressive spinal cord injury on neuroanatomical plasticity and kinematics. PLoS One. 9:e1110722014. View Article : Google Scholar : PubMed/NCBI
18	Janzadeh A, Sarveazad A, Yousefifard M, Dameni S, Samani FS, Mokhtarian K and Nasirinezhad F: Combine effect of Chondroitinase ABC and low level laser (660 nm) on spinal cord injury model in adult male rats. Neuropeptides. 65:90–99. 2017. View Article : Google Scholar : PubMed/NCBI
19	Sarveazad A, Babahajian A, Bakhtiari M, Soleimani M, Behnam B, Yari A, Akbari A, Yousefifard M, Janzadeh A, Amini N, et al: The combined application of human adipose derived stem cells and Chondroitinase ABC in treatment of a spinal cord injury model. Neuropeptides. 61:39–47. 2017. View Article : Google Scholar : PubMed/NCBI
20	Xia T, Huang B, Ni S, Gao L, Wang J, Wang J, Chen A, Zhu S, Wang B, Li G, et al: The combination of db-cAMP and ChABC with poly(propylene carbonate) microfibers promote axonal regenerative sprouting and functional recovery after spinal cord hemisection injury. Biomed Pharmacother. 86:354–362. 2017. View Article : Google Scholar : PubMed/NCBI
21	Hall ED: Inhibition of lipid peroxidation in CNS trauma. J Neurotrauma. 8 Suppl 1:S31–S41. 1991.PubMed/NCBI
22	Dayan K, Keser A, Konyalioglu S, Erturk M, Aydin F, Sengul G and Dagci T: The effect of hyperbaric oxygen on neuroregeneration following acute thoracic spinal cord injury. Life Sci. 90:360–364. 2012. View Article : Google Scholar : PubMed/NCBI
23	Geng CK, Cao HH, Ying X, Zhang HT and Yu HL: The effects of hyperbaric oxygen on macrophage polarization after rat spinal cord injury. Brain Res. 1606:68–76. 2015. View Article : Google Scholar : PubMed/NCBI
24	Thompson CD, Zurko JC, Hanna BF, Hellenbrand DJ and Hanna A: The therapeutic role of interleukin-10 after spinal cord injury. J Neurotrauma. 30:1311–1324. 2013. View Article : Google Scholar : PubMed/NCBI
25	Rong H, Liu Y, Zhao Z, Feng J, Sun R, Ma Z and Gu X: Further standardization in the aneurysm clip: The effects of occlusal depth on the outcome of spinal cord injury in rats. Spine (Phila Pa 1976). 43:E126–E131. 2018. View Article : Google Scholar : PubMed/NCBI
26	Basso DM, Beattie MS and Bresnahan JC: A sensitive and reliable locomotor rating scale for open field testing in rats. J Neurotrauma. 12:1–21. 1995. View Article : Google Scholar : PubMed/NCBI
27	Turner RC, Seminerio MJ, Naser ZJ, Ford JN, Martin SJ, Matsumoto RR, Rosen CL and Huber JD: Effects of aging on behavioral assessment performance: Implications for clinically relevant models of neurological disease. J Neurosurg. 117:629–637. 2012. View Article : Google Scholar : PubMed/NCBI
28	Nagai J, Owada K, Kitamura Y, Goshima Y and Ohshima T: Inhibition of CRMP2 phosphorylation repairs CNS by regulating neurotrophic and inhibitory responses. Exp Neurol. 277:283–295. 2016. View Article : Google Scholar : PubMed/NCBI
29	Nesic O, Guest JD, Zivadinovic D, Narayana PA, Herrera JJ, Grill RJ, Mokkapati VU, Gelman BB and Lee J: Aquaporins in spinal cord injury: The janus face of aquaporin 4. Neuroscience. 168:1019–1035. 2010. View Article : Google Scholar : PubMed/NCBI
30	Nesic O, Lee J, Ye Z, Unabia GC, Rafati D, Hulsebosch CE and Perez-Polo JR: Acute and chronic changes in aquaporin 4 expression after spinal cord injury. Neuroscience. 143:779–792. 2006. View Article : Google Scholar : PubMed/NCBI
31	Shechter R, Raposo C, London A, Sagi I and Schwartz M: The glial scar-monocyte interplay: A pivotal resolution phase in spinal cord repair. PLoS One. 6:e279692011. View Article : Google Scholar : PubMed/NCBI
32	Cuzzocrea S, Genovese T, Mazzon E, Crisafulli C, Di Paola R, Muià C, Collin M, Esposito E, Bramanti P and Thiemermann C: Glycogen synthase kinase-3 beta inhibition reduces secondary damage in experimental spinal cord trauma. J Pharmacol Exp Ther. 318:79–89. 2006. View Article : Google Scholar : PubMed/NCBI
33	Zeng Y, Ebong EE, Fu BM and Tarbell JM: The structural stability of the endothelial glycocalyx after enzymatic removal of glycosaminoglycans. PLoS One. 7:e431682012. View Article : Google Scholar : PubMed/NCBI
34	Xia Y, Yan Y, Xia H, Zhao T, Chu W, Hu S, Feng H and Lin J: Antisense vimentin cDNA combined with chondroitinase ABC promotes axon regeneration and functional recovery following spinal cord injury in rats. Neurosci Lett. 590:74–79. 2015. View Article : Google Scholar : PubMed/NCBI
35	Ni S, Xia T, Li X, Zhu X, Qi H, Huang S and Wang J: Sustained delivery of chondroitinase ABC by poly(propylene carbonate)-chitosan micron fibers promotes axon regeneration and functional recovery after spinal cord hemisection. Brain Res. 1624:469–478. 2015. View Article : Google Scholar : PubMed/NCBI
36	Didangelos A, Iberl M, Vinsland E, Bartus K and Bradbury EJ: Regulation of IL-10 by chondroitinase ABC promotes a distinct immune response following spinal cord injury. J Neurosci. 34:16424–16432. 2014. View Article : Google Scholar : PubMed/NCBI
37	Kingwell K: Spinal cord injury: Clamping down on calpains to treat injury-induced spasticity. Nat Rev Drug Discov. 15:3102016. View Article : Google Scholar : PubMed/NCBI
38	Zeng Y: Endothelial glycocalyx: Novel insight into atherosclerosis. J Biomed. 2:109–116. 2017. View Article : Google Scholar
39	Zeng Y: Endothelial glycocalyx as a critical signalling platform integrating the extracellular haemodynamic forces and chemical signalling. J Cell Mol Med. 21:1457–1462. 2017. View Article : Google Scholar : PubMed/NCBI
40	Iwahashi K, Hayashi T, Watanabe R, Nishimura A, Ueta T, Maeda T and Shiba K: Effects of orthotic therapeutic electrical stimulation in the treatment of patients with paresis associated with acute cervical spinal cord injury: A randomized control trial. Spinal Cord. Jun 27–2017.(Epub ahead of print). View Article : Google Scholar : PubMed/NCBI
41	Shultz RB and Zhong Y: Minocycline targets multiple secondary injury mechanisms in traumatic spinal cord injury. Neural Regen Res. 12:702–713. 2017. View Article : Google Scholar : PubMed/NCBI
42	Cabrera-Aldana EE, Ruelas F, Aranda C, Rincon-Heredia R, Martínez-Cruz A, Reyes-Sánchez A, Guizar-Sahagún G and Tovar-Y-Romo LB: Methylprednisolone administration following spinal cord injury reduces aquaporin 4 expression and exacerbates edema. Mediators Inflamm. 2017:47929322017. View Article : Google Scholar : PubMed/NCBI
43	Tatar S, Orhan N, Yilmaz CU, Arican N, Ahishali B, Kucuk M, Elmas I, Kaya M and Toklu AS: Hyperbaric oxygen therapy for five days increases blood-brain barrier permeability. Undersea Hyperb Med. 44:345–355. 2017. View Article : Google Scholar : PubMed/NCBI