Browsing by Subject "Chondroitin ABC Lyase"
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Item Open Access A simple technique for augmentation of axonal ingrowth into chondroitinase-treated acellular nerve grafts using nerve growth factor.(Annals of plastic surgery, 2012-05) Ovalle, Fernando; Patel, Ashit; Pollins, Alonda; de la Torre, Jorge; Vasconez, Luis; Hunt, Thomas R; Bucy, R Pat; Shack, R Bruce; Thayer, Wesley PBackground and purpose
Improvement in axonal regeneration may lead to the development of longer nerve grafts and improved outcomes for patients with peripheral nerve injury. Although the use of acellular nerve grafts has been well documented (Groves et al, Exp Neurol. 2005;195:278-292; Krekoski et al, J Neurosci. 2001;21:6206-6213; Massey et al, Exp Neurol. 2008;209:426-445; Neubauer et al, Exp Neurol. 2007;207:163-170; Zuo et al, Exp Neurol. 2002;176:221-228), less is known about the ability of neurotrophic factors to enhance axonal regeneration. This study evaluates axonal ingrowth augmentation using acellular, chondroitinase-treated nerve grafts doped with nerve growth factor (NGF).Methods
Acellular chondroitinase-treated murine nerve grafts were placed in experimental (NGF-treated grafts) and control (carrier-only grafts) rats. Five days after implantation, axonal regeneration was assessed by immunocytochemistry along with digital image analysis.Results
Higher axon count was observed throughout the length of the nerve in the NGF group (P < 0.0001), peaking at 3 mm from proximal repair (P = 0.02). Although the NGF group displayed a higher axon count per slice, the mean diameter of individual NGF axons was smaller (P < 0.0001), potentially consistent with induction of sensory axons (Rich et al, J Neurocytol. 1987;16:261-268; Sofroniew et al, Annu Rev Neurosci. 2001;24:1217-1128; Yip et al, J Neurosci. 1984;4:2986-2992).Conclusion
The simple technique of doping acellular, chondroitinase-treated nerve grafts with NGF can augment axonal ingrowth and possibly preferentially induce sensory axons.Item Open Access Axonal regrowth after spinal cord injury via chondroitinase and the tissue plasminogen activator (tPA)/plasmin system.(The Journal of neuroscience : the official journal of the Society for Neuroscience, 2011-10) Bukhari, Noreen; Torres, Luisa; Robinson, John K; Tsirka, Stella ESpinal cord injury (SCI) causes permanent debilitation due to the inability of axons to grow through established scars. Both the sugar chains and core proteins of chondroitin sulfate proteoglycans (CSPGs) are inhibitory for neurite regrowth. Chondroitinase ABC (ChABC) degrades the sugar chains and allows for synaptic plasticity, suggesting that after the sugar chain cleavage additional steps occur promoting a permissive microenvironment in the glial scar region. We report that the clearance of the core protein by the tissue plasminogen activator (tPA)/plasmin proteolytic system partially contributes to ChABC-promoted plasticity. tPA and plasmin are upregulated after SCI and degrade the deglycosylated CSPG proteins. Mice lacking tPA (tPA(-/-)) exhibit attenuated neurite outgrowth and blunted sensory and motor recovery despite ChABC treatment. Coadministration of ChABC and plasmin enhanced the tPA(-/-) phenotype and supported recovery in WT SCI mice. Collectively, these findings show that the tPA/plasmin cascade may act downstream of ChABC to allow for synergistic sensory and motor improvement compared with each treatment alone and suggest a potential new approach to enhance functional recovery after SCI.