Brachial plexus avulsion often results in massive motor neuron death and severe functional deficits of target muscles. However, no satisfactory treatment is currently available. Hypoxia-inducible factor 1α is a criti...Brachial plexus avulsion often results in massive motor neuron death and severe functional deficits of target muscles. However, no satisfactory treatment is currently available. Hypoxia-inducible factor 1α is a critical molecule targeting several genes associated with ischemia-hypoxia damage and angiogenesis. In this study, a rat model of brachial plexus avulsion-reimplantation was established, in which C5–7 ventral nerve roots were avulsed and only the C6 root reimplanted. Different implants were immediately injected using a microsyringe into the avulsion-reimplantation site of the C6 root post-brachial plexus avulsion. Rats were randomly divided into five groups: phosphate-buffered saline, negative control of lentivirus, hypoxia-inducible factor 1α(hypoxia-inducible factor 1α overexpression lentivirus), gel(pluronic F-127 hydrogel), and gel + hypoxia-inducible factor 1α(pluronic F-127 hydrogel + hypoxia-inducible factor 1α overexpression lentivirus). The Terzis grooming test was performed to assess recovery of motor function. Scores were higher in the hypoxia-inducible factor 1α and gel +hypoxia-inducible factor 1α groups(in particular the gel + hypoxia-inducible factor 1α group) compared with the phosphate-buffered saline group. Electrophysiology, fluorogold retrograde tracing, and immunofluorescent staining were further performed to investigate neural pathway reconstruction and changes of neurons, motor endplates, and angiogenesis. Compared with the phosphate-buffered saline group, action potential latency of musculocutaneous nerves was markedly shortened in the hypoxia-inducible factor 1α and gel + hypoxia-inducible factor1α groups. Meanwhile, the number of fluorogold-positive cells and ChAT-positive neurons, neovascular area(labeled by CD31 around av ulsed sites in ipsilateral spinal cord segments), and the number of motor endplates in biceps brachii(identified by α-bungarotoxin) were all visibly increased, as well as the morphology of motor endplate in biceps brachil was clear in the hypoxia-inducible factor 1α and gel + hypoxia-inducible factor 1α groups. Taken together, delivery of hypoxia-inducible factor 1α overexpression lentiviral vectors mediated by pluronic F-127 effectively promotes spinal root regeneration and functional recovery post-brachial plexus avulsion. All animal procedures were approved by the Institutional Animal Care and Use Committee of Guangdong Medical University, China.展开更多
In this study,we report the feasibility of Pluronic"F-127"as a lubricant for CoCrMo/ultrahigh molecular weight polyethylene(UHMWPE)interface in serum as a synovial fluid(SyF)model.While adsorption and lubric...In this study,we report the feasibility of Pluronic"F-127"as a lubricant for CoCrMo/ultrahigh molecular weight polyethylene(UHMWPE)interface in serum as a synovial fluid(SyF)model.While adsorption and lubrication properties of amphiphilic copolymers such as F-127 at a hydrophobic surface in aqueous media have been well established,its efficacy in serum can be more complicated due to potential interaction of F-127 with serum proteins or competitive adsorption onto UHMWPE surface.When an aliquot of F-127 solution(in concentration range of F-127 from 0.1%to 20%dissolved in 4-(2-hydroxyethyl)-1-piperazineethanesulfonic acid(HEPES))was added into serum where a CoCrMo pin is sliding against a UHMWPE disk,an immediate decrease in the coefficient of friction(COF)(ca.20%)was observed.A spectroscopy study employing dynamic light scattering(DLS),circular dichroism(CD)spectroscopy,and ultraviolet(UV)absorbance spectroscopy has shown that serum associatively interacts with F-127 when the F-127 concentration is above critical micelle concentration(CMC),leading to an increase in hydrodynamic size and alteration of tertiary structure of proteins in serum.Mixing of F-127 with the solutions of selected single component biomolecules of serum showed that γ-globulin is the primary molecule that interacts with F-127 above CMC,followed by albumin.Meanwhile,no indication of interaction was observed when the F-127 concentration was below CMC.It is thus proposed that the observed lubricating effect of F-127 in serum is primarily due to the faster surface adsorption kinetics for its smaller molecular weight compared to serum proteins.Further,comparable%reduction in COF over a wide range of F-127 concentration indicates that unimeric F-127 molecules are dominant in contribution to friction-lowering effect even at above CMC at CoCrMo/UHMWPE interface in serum.展开更多
基金financially supported by the National Natural Science Foundation of China,No.81371366(to HFW)the Natural Science Foundation of Guangdong Province of China,No.2015A030313515(to HFW)+1 种基金the Dongguan International Science and Technology Cooperation Project,No.2013508152010(to HFW)the Key Project of Social Development of Dongguan of China,No.20185071521640(to HFW)
文摘Brachial plexus avulsion often results in massive motor neuron death and severe functional deficits of target muscles. However, no satisfactory treatment is currently available. Hypoxia-inducible factor 1α is a critical molecule targeting several genes associated with ischemia-hypoxia damage and angiogenesis. In this study, a rat model of brachial plexus avulsion-reimplantation was established, in which C5–7 ventral nerve roots were avulsed and only the C6 root reimplanted. Different implants were immediately injected using a microsyringe into the avulsion-reimplantation site of the C6 root post-brachial plexus avulsion. Rats were randomly divided into five groups: phosphate-buffered saline, negative control of lentivirus, hypoxia-inducible factor 1α(hypoxia-inducible factor 1α overexpression lentivirus), gel(pluronic F-127 hydrogel), and gel + hypoxia-inducible factor 1α(pluronic F-127 hydrogel + hypoxia-inducible factor 1α overexpression lentivirus). The Terzis grooming test was performed to assess recovery of motor function. Scores were higher in the hypoxia-inducible factor 1α and gel +hypoxia-inducible factor 1α groups(in particular the gel + hypoxia-inducible factor 1α group) compared with the phosphate-buffered saline group. Electrophysiology, fluorogold retrograde tracing, and immunofluorescent staining were further performed to investigate neural pathway reconstruction and changes of neurons, motor endplates, and angiogenesis. Compared with the phosphate-buffered saline group, action potential latency of musculocutaneous nerves was markedly shortened in the hypoxia-inducible factor 1α and gel + hypoxia-inducible factor1α groups. Meanwhile, the number of fluorogold-positive cells and ChAT-positive neurons, neovascular area(labeled by CD31 around av ulsed sites in ipsilateral spinal cord segments), and the number of motor endplates in biceps brachii(identified by α-bungarotoxin) were all visibly increased, as well as the morphology of motor endplate in biceps brachil was clear in the hypoxia-inducible factor 1α and gel + hypoxia-inducible factor 1α groups. Taken together, delivery of hypoxia-inducible factor 1α overexpression lentiviral vectors mediated by pluronic F-127 effectively promotes spinal root regeneration and functional recovery post-brachial plexus avulsion. All animal procedures were approved by the Institutional Animal Care and Use Committee of Guangdong Medical University, China.
基金the VILLUM Foundation for their financial support(The VILLUM Experiment Programme,Project#17541).
文摘In this study,we report the feasibility of Pluronic"F-127"as a lubricant for CoCrMo/ultrahigh molecular weight polyethylene(UHMWPE)interface in serum as a synovial fluid(SyF)model.While adsorption and lubrication properties of amphiphilic copolymers such as F-127 at a hydrophobic surface in aqueous media have been well established,its efficacy in serum can be more complicated due to potential interaction of F-127 with serum proteins or competitive adsorption onto UHMWPE surface.When an aliquot of F-127 solution(in concentration range of F-127 from 0.1%to 20%dissolved in 4-(2-hydroxyethyl)-1-piperazineethanesulfonic acid(HEPES))was added into serum where a CoCrMo pin is sliding against a UHMWPE disk,an immediate decrease in the coefficient of friction(COF)(ca.20%)was observed.A spectroscopy study employing dynamic light scattering(DLS),circular dichroism(CD)spectroscopy,and ultraviolet(UV)absorbance spectroscopy has shown that serum associatively interacts with F-127 when the F-127 concentration is above critical micelle concentration(CMC),leading to an increase in hydrodynamic size and alteration of tertiary structure of proteins in serum.Mixing of F-127 with the solutions of selected single component biomolecules of serum showed that γ-globulin is the primary molecule that interacts with F-127 above CMC,followed by albumin.Meanwhile,no indication of interaction was observed when the F-127 concentration was below CMC.It is thus proposed that the observed lubricating effect of F-127 in serum is primarily due to the faster surface adsorption kinetics for its smaller molecular weight compared to serum proteins.Further,comparable%reduction in COF over a wide range of F-127 concentration indicates that unimeric F-127 molecules are dominant in contribution to friction-lowering effect even at above CMC at CoCrMo/UHMWPE interface in serum.
