Abstract:This preliminary study firstly demonstrated the effectiveness of TeTx on nerve repair in experimental sciatic rat model based on functional, electromyographic and histological parameters.
“…A variety of therapeutic modalities have been adopted by physicians to achieve recovery in animal models, yet attaining fully functional recovery is still a challenge to be addressed ( Hussain et al, 2020 ). Many antioxidants (vitamin E, ubiquinone, and L-carnitine) ( Karsidag et al, 2012 ; Azizi et al, 2014 ; Moradi et al, 2014 ), anti-inflammatories (dexamethasone and acetylsalicylic acid) ( Subbanna et al, 2007 ; Feng and Yuan, 2015 ), or other substances (diphosphocholine, rapamycin, and tetanus toxin) ( Gunay et al, 2014 ; Ding et al, 2015 ; Emril et al, 2016 ) have been tried. However, few effective clinical drug treatments are available.…”
BackgroundThe majority of the suggested experimental modalities for peripheral nerve injury (PNI) result in varying degrees of recovery in animal models; however, there are not many reliable clinical pharmacological treatment models available. To alleviate PNI complications, research on approaches to accelerate peripheral nerve regeneration is encouraged. Cerebrolysin, dexamethasone, and ascorbic acid (vitamin C) drug models were selected in our study because of their reported curative effects of different mechanisms of action.MethodologyA total of 40 adult male albino rats were used in this study. Sciatic nerve crush injury was induced in 32 rats, which were divided equally into four groups (model, Cerebrolysin, dexamethasone, and vitamin C groups) and compared to the sham group (n = 8). The sciatic nerve sensory and motor function regeneration after crushing together with gastrocnemius muscle histopathological changes were evaluated by the sciatic function index, the hot plate test, gastrocnemius muscle mass ratio, and immune expression of S100 and apoptosis cascade (BAX, BCL2, and BAX/BCL2 ratio).ResultsSignificant improvement of the behavioral status and histopathological assessment scores occurred after the use of Cerebrolysin (as a neurotrophic factor), dexamethasone (as an anti-inflammatory), and vitamin C (as an antioxidant). Despite these seemingly concomitant, robust behavioral and pathological changes, vitamin C appeared to have the best results among the three main outcome measures. There was a positive correlation between motor and sensory improvement and also between behavioral and histopathological changes, boosting the effectiveness, and implication of the sciatic function index as a mirror for changes occurring on the tissue level.ConclusionVitamin C is a promising therapeutic in the treatment of PNI. The sciatic function index (SFI) test is a reliable accurate method for assessing sciatic nerve integrity after both partial disruption and regrowth.
“…A variety of therapeutic modalities have been adopted by physicians to achieve recovery in animal models, yet attaining fully functional recovery is still a challenge to be addressed ( Hussain et al, 2020 ). Many antioxidants (vitamin E, ubiquinone, and L-carnitine) ( Karsidag et al, 2012 ; Azizi et al, 2014 ; Moradi et al, 2014 ), anti-inflammatories (dexamethasone and acetylsalicylic acid) ( Subbanna et al, 2007 ; Feng and Yuan, 2015 ), or other substances (diphosphocholine, rapamycin, and tetanus toxin) ( Gunay et al, 2014 ; Ding et al, 2015 ; Emril et al, 2016 ) have been tried. However, few effective clinical drug treatments are available.…”
BackgroundThe majority of the suggested experimental modalities for peripheral nerve injury (PNI) result in varying degrees of recovery in animal models; however, there are not many reliable clinical pharmacological treatment models available. To alleviate PNI complications, research on approaches to accelerate peripheral nerve regeneration is encouraged. Cerebrolysin, dexamethasone, and ascorbic acid (vitamin C) drug models were selected in our study because of their reported curative effects of different mechanisms of action.MethodologyA total of 40 adult male albino rats were used in this study. Sciatic nerve crush injury was induced in 32 rats, which were divided equally into four groups (model, Cerebrolysin, dexamethasone, and vitamin C groups) and compared to the sham group (n = 8). The sciatic nerve sensory and motor function regeneration after crushing together with gastrocnemius muscle histopathological changes were evaluated by the sciatic function index, the hot plate test, gastrocnemius muscle mass ratio, and immune expression of S100 and apoptosis cascade (BAX, BCL2, and BAX/BCL2 ratio).ResultsSignificant improvement of the behavioral status and histopathological assessment scores occurred after the use of Cerebrolysin (as a neurotrophic factor), dexamethasone (as an anti-inflammatory), and vitamin C (as an antioxidant). Despite these seemingly concomitant, robust behavioral and pathological changes, vitamin C appeared to have the best results among the three main outcome measures. There was a positive correlation between motor and sensory improvement and also between behavioral and histopathological changes, boosting the effectiveness, and implication of the sciatic function index as a mirror for changes occurring on the tissue level.ConclusionVitamin C is a promising therapeutic in the treatment of PNI. The sciatic function index (SFI) test is a reliable accurate method for assessing sciatic nerve integrity after both partial disruption and regrowth.
“…Furthermore, several reports indicate that the C-terminus may have an antiapoptotic effect on neurons [ 5 – 7 ] . Both in vitro and in vivo studies have shown that the TTC induces neuroprotection [ 5 , 8 , 9 ]. Fig.…”
BackgroundTetanus neurotoxin (TeNT) is taken up at nerve terminals and undergoes retrograde migration. The toxic properties of TeNT reside in the toxin light chain (L), but like complete TeNT, the TeNT heavy chain (TTH) and the C-terminal domain (TTC) alone can bind and enter into neurons. Here, we explored whether atoxic fragments of TeNT could act as drug delivery vehicles in neurons. In this study, we used Bcl-2, a protein known to have anti-apoptotic properties in vivo and in vitro, as a parcel to couple to TeNT fragments.ResultsWe expressed Bcl-2 and the TTC fragments alone, and also attempted to express fusion proteins with the Bcl-2 coupled at the N-terminus of TTH (Bcl2-TTH) and the N- and C-terminus of TTC (TTC-Bcl2 and Bcl2-TTC) in mammalian (Cos7 cells) and Escherichia coli systems. TTC and Bcl-2 were efficiently expressed in E. coli and Cos7 cells, respectively, but Bcl-2 and the fusion proteins did not express well in E. coli. The fusion proteins were also not expressed in Cos7 cells. To improve the yield and purity of the fusion protein, we genetically deleted the N-terminal half of TTC from the Bcl2-TTC fusion to yield Bcl2-hTTC. Purified Bcl2-hTTC exhibited neuronal binding and prevented cell death of neuronal PC12 cells induced by serum and NGF deprivation, as evidenced by the inhibition of cytochrome C release from the mitochondria. For in vivo assays, Bcl2-hTTC was injected into the tongues of mice and was seen to selectively migrate to hypoglossal nuclei mouse brain stems via retrograde axonal transport.ConclusionsThese results indicate that Bcl2-hTTC retains both Bcl-2 and TTC functions and therefore could be a potent therapeutic agent for various neurological conditions.
“…An accumulation of released neurotrophins, e.g., brain‐derived neurotrophic factor (BDNF) or nerve growth factor (NGF), is postulated in the isolated local regenerative milieu within conduits . Recent studies investigate effects of additional administration of platelet rich plasma and platelet rich fibrin in silicone tubes or tetanus toxin on side of sciatic nerve lesion to facilitate nerve regeneration . Also various growth factors, like IGF‐1 or VEGF, were locally applied to improve peripheral nerve regeneration .…”
mentioning
confidence: 99%
“…2 Recent studies investigate effects of additional administration of platelet rich plasma and platelet rich fibrin in silicone tubes or tetanus toxin on side of sciatic nerve lesion to facilitate nerve regeneration. 4,5 Also various growth factors, like IGF-1 or VEGF, were locally applied to improve peripheral nerve regeneration. 6,7 For longer nerve gaps, nerve conduits serve as guiding structures for sprouting axons.…”
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