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Abstract Background: Spinal ventral root injuries generate significant motoneuron degeneration, which hinders full functional recovery. The poor prognosis of functional recovery can be attributed to the use or combination of different therapeutic approaches. Several molecules have been screened as potential treatments in combination with surgical reimplantation of the avulsed roots, the gold standard approach for such injuries. Among the studied molecules, human natural killer-1 (HNK-1) stands out as it is related to the stimulation of motor axon outgrowth. Therefore, we aimed to comparatively investigate the effects of local administration of an HNK-1 mimetic peptide (mp-HNK-1) and systemic treatment with ursolic acid (UA), another HNK-1 mimetic, after ventral root avulsion and reimplantation with heterologous fibrin biopolymer (HFB). Methods: Female mice of the isogenic strain C57BL/6JUnib were divided into five experimental groups: Avulsion, Reimplantation, mp-HNK-1 (in situ), and UA (systemic treatment). Mice were evaluated 2 and 12 weeks after surgery. Functional assessment was performed every four days using the Catwalk platform. Neuronal survival was analyzed by cytochemistry, and glial reactions and synaptic coverage were evaluated by immunofluorescence. Results: Treatment with UA elicited long-term neuroprotection, accompanied by a decrease in microglial reactions, and reactive astrogliosis. The neuroprotective effects of UA were preceded by increased glutamatergic and GABAergic inputs in the ventral spinal cord two weeks after injury. However, a single application of mp-HNK-1 had no significant effects. Functional analysis showed that UA treatment led to an improvement in motor and sensory recovery. Conclusion: Overall, the results indicate that UA is neuroprotective, acting on glial cells and synaptic maintenance, and the combination of these findings led to a better functional recovery.

The present study aimed to evaluate the new heterologous fibrin biopolymer associated, or not, with photobiomodulation therapy for application in tendon injuries, considered a serious and common orthopedic problem. Thus, 84 Rattus norvegicus had partial transection of the calcaneus tendon (PTCT) and were randomly divided into: control (CG); heterologous fibrin biopolymer (HFB); photobiomodulation (PBM); heterologous fibrin biopolymer + photobiomodulation (HFB + PBM). The animals received HFB immediately after PTCT, while PBM (660 nm, 40 mW, 0.23 J) started 24 h post injury and followed every 24 h for 7, 14, and 21 days. The results of the edema volume showed that after 24 h of PTCT, there was no statistical difference among the groups. After 7, 14, and 21 days, it was observed that the treatment groups were effective in reducing edema when compared to the control. The HFB had the highest edema volume reduction after 21 days of treatment. The treatment groups did not induce tissue necrosis or infections on the histopathological analysis. Tenocyte proliferation, granulation tissue, and collagen formation were observed in the PTCT area in the HFB and HFB + PBM groups, which culminated a better repair process when compared to the CG in the 3 experimental periods. Interestingly, the PBM group revealed, in histological analysis, major tendon injury after 7 days; however, in the periods of 14 and 21 days, the PBM had a better repair process compared to the CG. In the quantification of collagen, there was no statistical difference between the groups in the 3 experimental periods. The findings suggest that the HFB and PBM treatments, isolated or associated, were effective in reducing the volume of the edema, stimulating the repair process. However, the use of HFB alone was more effective in promoting the tendon repair process. Thus, the present study consolidates previous studies of tendon repair with this new HFB. Future clinical trials will be needed to validate this proposal. [ABSTRACT FROM AUTHOR]

Denervation leads to severe atrophy of neuromuscular junction (NMJ) structure including decrease of the expression of fundamental proteins. Up to now, conventional suture has been the gold standard method used to correct this injury. Fibrin sealant is one of the alternatives proposed to optimize this method. This study verified if the association of fibrin sealant - Heterologous Fibrin Biopolymer (HFB) and a single suture stitch promotes return of morphology and NMJ structure to mature pattern after peripheral nerve injury. Forty Wistar rats were distributed into 4 groups: Sham-Control (SC), Denervated-Control (DC), Suture-Lesion (SL) and Suture-Lesion + HFB (SFS). In SC group only the right sciatic nerve identification was done. In DC, SL and SFS groups fixation of nerve stumps on musculature immediately after neurotmesis was performed. After seven days, stump reconnection with 3 stitches in SL and a single stitch associated with HFB in SFS were done. After sixty days right soleus muscles were prepared for nicotinic acetylcholine receptors (nAChRs) and nerve terminal confocal analyses, and for nAChRs (α1, ε e γ), S100, Agrin, LRP-4, MMP-3, Rapsyn western blotting analyses. SC group presented normal morphology. In DC group it was observed flattening of NMJ, fragmentation of nAChRs and tangled nerve terminals. The majority of the parameters of SL and SFS groups presented values in between SC and DC groups. There was an increase of relative planar area in these groups (SL and SFS) highlighting that there was less nAChRs fragmentation and the values of protein expression showed return of nAChRs to mature pattern. Use of HFB associated with a single suture stitch decreased surgical time, minimized suture injuries, did not alter nerve regeneration and presented potential to reestablish the NMJ apparatus. These consolidated results encourage surgeons to develop future clinical trials to install definitively this new approach both for reconstructive surgery and neurosurgery. [ABSTRACT FROM AUTHOR]

Background: Spinal ventral root injuries generate significant motoneuron degeneration, which hinders full functional recovery. The poor prognosis of functional recovery can be attributed to the use or combination of different therapeutic approaches. Several molecules have been screened as potential treatments in combination with surgical reimplantation of the avulsed roots, the gold standard approach for such injuries. Among the studied molecules, human natural killer-1 (HNK-1) stands out as it is related to the stimulation of motor axon outgrowth. Therefore, we aimed to comparatively investigate the effects of local administration of an HNK-1 mimetic peptide (mp-HNK-1) and systemic treatment with ursolic acid (UA), another HNK-1 mimetic, after ventral root avulsion and reimplantation with heterologous fibrin biopolymer (HFB)., Methods: Female mice of the isogenic strain C57BL/6JUnib were divided into five experimental groups: Avulsion, Reimplantation, mp-HNK-1 (in situ), and UA (systemic treatment). Mice were evaluated 2 and 12 weeks after surgery. Functional assessment was performed every four days using the Catwalk platform. Neuronal survival was analyzed by cytochemistry, and glial reactions and synaptic coverage were evaluated by immunofluorescence., Results: Treatment with UA elicited long-term neuroprotection, accompanied by a decrease in microglial reactions, and reactive astrogliosis. The neuroprotective effects of UA were preceded by increased glutamatergic and GABAergic inputs in the ventral spinal cord two weeks after injury. However, a single application of mp-HNK-1 had no significant effects. Functional analysis showed that UA treatment led to an improvement in motor and sensory recovery., Conclusion: Overall, the results indicate that UA is neuroprotective, acting on glial cells and synaptic maintenance, and the combination of these findings led to a better functional recovery., Competing Interests: Competing interests: The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest.