Responsive Calcium (Ca2+) Alginate-Chitosan Based Hydrogel: A Promising Biomaterial for Spinal Cord Injury

2021 ◽  
Vol 52 ◽  
pp. 29-37
Author(s):  
Fulky A'yunni ◽  
Prihartini Widiyanti ◽  
Dyah Hikmawati
Keyword(s):  
Spinal Cord ◽  
Spinal Cord Injury ◽  
Neuronal Loss ◽  
Assay Method ◽  
Cytotoxicity Test ◽  
Permanent Disability ◽  
Chitosan Hydrogel ◽  
Cell Percentage ◽  
Cord Injury ◽  
Hydrogel Synthesis

Spinal cord injury is damage to the spinal cord which causes lesions in the spinal cord and leads to an increase in extracellular Ca2+. It results in additional neuronal loss which causes temporary/permanent disability or even death. The aim of this study was to determine characteristics and the best composition of alginate – chitosan hydrogel responsive to Calcium (Ca2+) for spinal cord injury. Hydrogel synthesis with its compositions, namely chitosan was dissolved in 0.4% acetic acid, neutralized in pH 7 with 0.5 M NaOH, added some 0.85% NaCl in it, and added 5 alginate variations which were dissolved in 0.85% NaCl, next will centrifugation method. Based on the FTIR test, hydrogel showed stretching vibrations of Chitosan’s O–H bonds appeared in 3415.93cm-1 wavenumber, while Na groups of alginate isomer appeared in 1413.82 cm-1 wavenumber. The results of the cytotoxicity test using the MTT Assay method showed live cell percentage from less than 50% to 52.61% in Sample B and 83.83% in Sample C. The results of the injectability test showed that all samples were injectable with the highest percentage of injectability at 98.283%. The results of the UV-Vis spectrophotometric test showed that all hydrogel samples were able to absorb Ca2+. Hydrogels can be degraded at more than 90% within 14 days. The results of the morphology test (SEM) obtained 84.7-99.6 μm pore sizes.

scholarly journals Inhibition of Caspase-1 by VX-765 Reduces Pyroptosis and Attenuates Neuroinflammation After Spinal Cord Injury

2020 ◽  
Author(s):  
Liulong Zhu ◽  
Fan He ◽  
Guoming Ding ◽  
Maoqiang Li ◽  
Wu Jiang
Keyword(s):  
Spinal Cord ◽  
Spinal Cord Injury ◽  
Proinflammatory Cytokines ◽  
Neuronal Loss ◽  
Glucose Deprivation ◽  
Enzyme Linked Immunosorbent Assay ◽  
Caspase 1 ◽  
Therapy Strategy ◽  
Cord Injury ◽  
Underlying Mechanisms

Abstract Background: Excessive inflammatory response, neuronal loss, and demyelination mediate the pathogenesis of spinal cord injury (SCI). VX-765, a highly selective caspase-1 inhibitor, is recently revealed to control pyroptosis in some disease models. However, the effects and underlying mechanisms of VX-765 in SCI remains unclear. Methods: Functional recovery was assessed using Basso Mouse Scale (BMS) and BMS subscore. Proinflammatory cytokines levels was evaluated by western blot or enzyme-linked immunosorbent assay. The number of neutrophils was assessed by flow cytometry. Neuronal loss was evaluated by immunochemistry staining of NeuN. Demyelination was evaluated using immunofluorescence staining of myelin basic protein. Results: Here we report that VX-765 led to a significant recovery of hindlimb locomotor function after SCI in mice. Moreover, VX-765 prevented caspase-1 activation, inhibited pyroptosis of neuron and oligodendrocyte, reduced proinflammatory cytokines levels and loss of neuron and myelin, and declines the number of neutrophils in mice. Furthermore, VX-765 suppressed caspase-1 activation, decreased proinflammatory cytokine levels, diminished pyroptosis and promoted the survival of neurons in oxygen-glucose deprivation oligodendrocytes.Conclusions: Together, our data indicate that VX-765 provide a novel potential therapy strategy to improve recovery after SCI.

Resident Neural Stem Cells Restrict Tissue Damage and Neuronal Loss After Spinal Cord Injury in Mice

Science ◽  
2013 ◽  
Vol 342 (6158) ◽  
pp. 637-640 ◽  
Author(s):  
H. Sabelstrom ◽  
M. Stenudd ◽  
P. Reu ◽  
D. O. Dias ◽  
M. Elfineh ◽  
...  
Keyword(s):  
Spinal Cord ◽  
Stem Cells ◽  
Spinal Cord Injury ◽  
Neural Stem Cells ◽  
Tissue Damage ◽  
Neuronal Loss ◽  
Cord Injury

scholarly journals Retrograde Activation of the Extrinsic Apoptotic Pathway in Spinal-Projecting Neurons after a Complete Spinal Cord Injury in Lampreys

2017 ◽  
Vol 2017 ◽  
pp. 1-12 ◽  
Author(s):  
Antón Barreiro-Iglesias ◽  
Daniel Sobrido-Cameán ◽  
Michael I. Shifman
Keyword(s):  
Spinal Cord ◽  
Spinal Cord Injury ◽  
Molecular Mechanisms ◽  
Extrinsic Pathway ◽  
Apoptotic Pathway ◽  
Permanent Disability ◽  
Descending Neurons ◽  
Neuronal Soma ◽  
Cord Injury ◽  
Complete Spinal Cord Injury

Spinal cord injury (SCI) is a devastating condition that leads to permanent disability because injured axons do not regenerate across the trauma zone to reconnect to their targets. A prerequisite for axonal regeneration will be the prevention of retrograde degeneration that could lead to neuronal death. However, the specific molecular mechanisms of axotomy-induced degeneration of spinal-projecting neurons have not been elucidated yet. In lampreys, SCI induces the apoptotic death of identifiable descending neurons that are “bad regenerators/poor survivors” after SCI. Here, we investigated the apoptotic process activated in identifiable descending neurons of lampreys after SCI. For this, we studied caspase activation by using fluorochrome-labeled inhibitors of caspases, the degeneration of spinal-projecting neurons using Fluro-Jade C staining, and the involvement of the intrinsic apoptotic pathway by means of cytochrome c and Vαdouble immunofluorescence. Our results provide evidence that, after SCI, bad-regenerating spinal cord-projecting neurons slowly degenerate and that the extrinsic pathway of apoptosis is involved in this process. Experiments using the microtubule stabilizer Taxol showed that caspase-8 signaling is retrogradely transported by microtubules from the site of axotomy to the neuronal soma. Preventing the activation of this process could be an important therapeutic approach after SCI in mammals.

scholarly journals Therapeutic Potential of Mesenchymal Stem Cells (MSCs) and MSC-Derived Extracellular Vesicles for the Treatment of Spinal Cord Injury

2021 ◽  
Vol 22 (24) ◽  
pp. 13672
Author(s):  
Gang-Un Kim ◽  
Soo-Eun Sung ◽  
Kyung-Ku Kang ◽  
Joo-Hee Choi ◽  
Sijoon Lee ◽  
...  
Keyword(s):  
Spinal Cord ◽  
Spinal Cord Injury ◽  
Regenerative Medicine ◽  
Extracellular Vesicles ◽  
Structural Changes ◽  
Therapeutic Agent ◽  
Therapeutic Potential ◽  
Permanent Disability ◽  
Cord Injury ◽  
Anti Inflammatory

Spinal cord injury (SCI) is a life-threatening condition that leads to permanent disability with partial or complete loss of motor, sensory, and autonomic functions. SCI is usually caused by initial mechanical insult, followed by a cascade of several neuroinflammation and structural changes. For ameliorating the neuroinflammatory cascades, MSC has been regarded as a therapeutic agent. The animal SCI research has demonstrated that MSC can be a valuable therapeutic agent with several growth factors and cytokines that may induce anti-inflammatory and regenerative effects. However, the therapeutic efficacy of MSCs in animal SCI models is inconsistent, and the optimal method of MSCs remains debatable. Moreover, there are several limitations to developing these therapeutic agents for humans. Therefore, identifying novel agents for regenerative medicine is necessary. Extracellular vesicles are a novel source for regenerative medicine; they possess nucleic acids, functional proteins, and bioactive lipids and perform various functions, including damaged tissue repair, immune response regulation, and reduction of inflammation. MSC-derived exosomes have advantages over MSCs, including small dimensions, low immunogenicity, and no need for additional procedures for culture expansion or delivery. Certain studies have demonstrated that MSC-derived extracellular vesicles (EVs), including exosomes, exhibit outstanding chondroprotective and anti-inflammatory effects. Therefore, we reviewed the principles and patho-mechanisms and summarized the research outcomes of MSCs and MSC-derived EVs for SCI, reported to date.

scholarly journals Curcumin exhibits therapeutic effect against spinal cord injury via inhibition of neuronal inflammation and apoptosis

2021 ◽  
Vol 18 (9) ◽  
pp. 1927-1933
Author(s):  
Wei Xiao ◽  
Xuewu Chen ◽  
Yijun Wang ◽  
Jianzhong Chang ◽  
Zufa Zhao ◽  
...  
Keyword(s):  
Spinal Cord ◽  
Spinal Cord Injury ◽  
Neuronal Loss ◽  
Cord Compression ◽  
Tunel Staining ◽  
Myeloperoxidase Activity ◽  
Curcumin Treatment ◽  
Thoracic Spinal Cord ◽  
Thoracic Spinal ◽  
Cord Injury

Purpose: To investigate the effect of curcumin on spinal cord injury (SCI) in a rat model. Methods: SCI was induced in the rats using mid thoracic spinal cord compression, after which curcumin was injected intraperitoneally. Western blotting was used for assay of expressions of apoptotic proteins, viz, IL-1β, NF-κB p65, TLR4, TNF-α, LC3, Bax and Bcl-2. Malondialdehyde (MDA) and myeloperoxidase were measured using standard methods. Neuronal loss in spinal cord tissues was determined with TUNEL staining and NeuN labelling. Results: Curcumin treatment significantly (p < 0.05) suppressed SCI-mediated upregulation of myeloperoxidase activity and increase in MDA level in rat spinal cord. The reduction of glutathione (GSH) and superoxide dismutase (SOD) activities in the spinal cord of SCI rats were suppressed by curcumin treatment. Curcumin treatment also led to a significant (p < 0.02) increase in the proportion of NeuN positive cells and marked reduction in TUNEL positive cells, but it decreased caspase-3 in the spinal cord tissues of SCI rats. Moreover, curcumin reversed the effect of SCI on protein expressions of Bax and Bcl 2 in a dose-based manner. There was marked curcumin-induced decline in CD11b and GFAP levels in the spinal cord tissues of the SCI rats. Conclusion: These results demonstrate that curcumin protects rats against SCI via inhibition of oxidative stress-mediated neuronal apoptosis. Therefore, curcumin may be useful for the development of an effective treatment for spinal cord injury.

scholarly journals Dopamine Reduced Pyroptosis and Improved Functional Recovery After Spinal Cord Injury 

2020 ◽  
Author(s):  
Liulong Zhu ◽  
Guoming Ding ◽  
Fan He ◽  
Maoqiang Li ◽  
Wu Jiang
Keyword(s):  
Spinal Cord ◽  
Spinal Cord Injury ◽  
Inflammatory Response ◽  
Functional Recovery ◽  
Nlrp3 Inflammasome ◽  
Molecular Mechanisms ◽  
Neuronal Loss ◽  
Inflammasome Activation ◽  
Nlrp3 Inflammasome Activation ◽  
Cord Injury

Abstract Background: Neuronal loss, demyelination, and an excessive inflammatory response accompany the pathogenesis of spinal cord injury (SCI). The inflammatory response is promoted by inflammasomes in variety diseases. Dopamine is a neurotransmitter that also functions as a regulator in NLRP3 (nucleotide-binding oligomerization domain-like receptor 3) inflammasome-dependent neuroinflammation. However, the effects and molecular mechanisms underlying the role of dopamine in SCI are little known. Methods:Functional recovery was assessed using Basso Mouse Scale (BMS) and BMS subscore. Histopathologic damage was evaluated by H&E staining. Demyelination was evaluated using immunofluorescence staining of myelin basic protein. Neuronal loss was evaluated by immunochemistry staining of NeuN. Pyroptosis was assessed by flow cytometry, western blot, and cell viability and cytotoxicity assays.Results: This study using mice showed that dopamine was significantly associated with enhanced locomotor recovery after SCI; with a reduction in NLRP3 inflammasome activation, pyroptosis, neuron and myelin loss, and histological changes. In vitro data suggested an association between dopamine and suppressed NLRP3 inflammasome activation and neuronal pyroptosis, and greater survival of neurons. Conclusion: Thus, dopamine may be a novel and effective approach for improving recovery after SCI.

scholarly journals Lentiviral Vectors Delivered with Biomaterials as Therapeutics for Spinal Cord Injury

Cells ◽  
2021 ◽  
Vol 10 (8) ◽  
pp. 2102
Author(s):  
Ciara Shortiss ◽  
Linda Howard ◽  
Siobhan S. McMahon
Keyword(s):  
Spinal Cord ◽  
Spinal Cord Injury ◽  
Molecular Mechanisms ◽  
Lentiviral Vectors ◽  
Therapeutic Effects ◽  
Nucleic Acid Delivery ◽  
Permanent Disability ◽  
Cord Injury ◽  
Socioeconomic Burden ◽  
Superior Approach

Spinal cord injury (SCI) is a devastating trauma that can cause permanent disability, life-long chronic issues for sufferers and is a big socioeconomic burden. Regenerative medicine aims to overcome injury caused deficits and restore function after SCI through gene therapy and tissue engineering approaches. SCI has a multifaceted pathophysiology. Due to this, producing therapies that target multiple different cellular and molecular mechanisms might prove to be a superior approach in attempts at regeneration. Both biomaterials and nucleic acid delivery via lentiviral vectors (LVs) have proven to promote repair and restoration of function post SCI in animal models. Studies indicate that a combination of biomaterials and LVs is more effective than either approach alone. This review presents studies supporting the use of LVs and LVs delivered with biomaterials in therapies for SCI and summarises methods to combine LVs with biomaterials for SCI treatment. By summarising this knowledge this review aims to demonstrate how LV delivery with biomaterials can augment/compliment both LV and biomaterial therapeutic effects in SCI.

scholarly journals GABA promotes survival and axonal regeneration in identifiable descending neurons after spinal cord injury in larval lampreys

2018 ◽  
Author(s):  
D Romaus-Sanjurjo ◽  
R Ledo-García ◽  
B Fernández-López ◽  
K Hanslik ◽  
JR Morgan ◽  
...  
Keyword(s):  
Spinal Cord ◽  
Spinal Cord Injury ◽  
Axonal Regeneration ◽  
Gabab Receptor ◽  
Gabab Receptors ◽  
Regenerative Capacity ◽  
Permanent Disability ◽  
Descending Neurons ◽  
Cord Injury

AbstractIn mammals, spinal cord injury (SCI) causes permanent disability. The poor regenerative capacity of descending neurons is one of the main causes of the lack of recovery after SCI. In addition, the prevention of retrograde degeneration leading to the atrophy or death of descending neurons is an obvious prerequisite for the activation of axonal regeneration. Lampreys show an amazing regenerative capacity after SCI. Recent histological work in lampreys suggested that GABA, which is massively released after a SCI, could promote the survival of descending neurons. Here, we aimed to study if GABA, acting through GABAB receptors, promotes the survival and axonal regeneration of descending neurons of larval sea lampreys after a complete SCI. First, we used in situ hybridization to confirm that identifiable descending neurons of late stage larvae express the gabab1 subunit of the sea lamprey GABAB receptor. We also observed an acute increase in the expression of this subunit in descending neurons after a complete SCI, which further supported the possible role of GABA and GABAB receptors in promoting the survival and regeneration of these neurons. So, we performed gain and loss of function experiments to confirm this hypothesis. Treatments with GABA and baclofen (GABAB agonist) significantly reduced caspase activation in descending neurons 2 weeks after a complete SCI. Long-term treatments with GABOB (a GABA analogue) and baclofen significantly promoted axonal regeneration of descending neurons after SCI. These data indicate that GABAergic signalling through GABAB receptors promotes the survival and regeneration of descending neurons after SCI. Finally, we used morpholinos against the gabab1 subunit to specifically knockdown the expression of the GABAB receptor in descending neurons. Long-term morpholino treatments caused a significant inhibition of axonal regeneration, which shows that endogenous GABA promotes axonal regeneration after a complete SCI in lampreys by activating GABAB receptors expressed in descending neurons. These data implicate GABAB receptors in spinal cord regeneration in lampreys and further provide a new target of interest for SCI.

scholarly journals Human umbilical cord mesenchymal stem cells-derived extracellular vesicles facilitate the repair of spinal cord injury via the miR-29b-3p/PTEN/Akt/mTOR axis

2021 ◽  
Vol 7 (1) ◽  
Author(s):  
Xiao Xiao ◽  
Weiwei Li ◽  
Dingchao Rong ◽  
Zhenchao Xu ◽  
Zhen Zhang ◽  
...  
Keyword(s):  
Spinal Cord ◽  
Stem Cells ◽  
Spinal Cord Injury ◽  
Mesenchymal Stem Cells ◽  
Umbilical Cord ◽  
Motor Function ◽  
Extracellular Vesicles ◽  
Human Umbilical Cord ◽  
Permanent Disability ◽  
Cord Injury

AbstractSpinal cord injury (SCI) is a salient traumatic disease that often leads to permanent disability, and motor and sensory impairments. Human umbilical cord mesenchymal stem cells (HucMSCs) have a wide application prospect in the treatment of SCI. This study explored the repair effect of HucMSCs-derived extracellular vesicles (HucMSCs-EVs) on SCI. HucMSCs and HucMSCs-EVs were cultured and identified. The rat model of SCI was established, and SCI rats were treated with HucMSCs-EVs. The motor function of SCI rats and morphology of spinal cord tissues were evaluated. Levels of NeuN, GFAP, and NF200 in spinal cord tissues were detected and cell apoptosis was measured. SCI rats were treated with EVs extracted from miR-29b-3p inhibitor-transfected HucMSCs. The downstream gene and pathway of miR-29b-3p were examined. HucMSCs-EVs-treated rats showed obvious motor function recovery and reduced necrosis, nuclear pyknosis, and cavity. HucMSCs-EVs alleviated spinal cord neuronal injury. miR-29b-3p was poorly expressed in SCI tissues, but highly expressed in EVs and SCI rats treated with EVs. miR-29b-3p targeted PTEN. Inhibition of miR-29b-3p or overexpression of PTEN reversed the repair effect of EVs on SCI. EVs activated the AKT/mTOR pathway via the miR-29b-3p/PTEN. In conclusion, HucMSCs-EVs reduced pathological changes, improved motor function, and promoted nerve function repair in SCI rats via the miR-29b-3p/PTEN/Akt/mTOR axis.

Extrinsic and intrinsic factors controlling axonal regeneration after spinal cord injury

2009 ◽  
Vol 11 ◽  
Author(s):  
Fardad T. Afshari ◽  
Sunil Kappagantula ◽  
James W. Fawcett
Keyword(s):  
Spinal Cord ◽  
Central Nervous System ◽  
Spinal Cord Injury ◽  
Nervous System ◽  
Functional Recovery ◽  
Extrinsic Factors ◽  
Permanent Disability ◽  
Intrinsic Factors ◽  
Cord Injury ◽  
The Central Nervous System

Spinal cord injury is one of the most devastating conditions that affects the central nervous system. It can lead to permanent disability and there are around two million people affected worldwide. After injury, accumulation of myelin debris and formation of an inhibitory glial scar at the site of injury leads to a physical and chemical barrier that blocks axonal growth and regeneration. The mammalian central nervous system thus has a limited intrinsic ability to repair itself after injury. To improve axonal outgrowth and promote functional recovery, it is essential to identify the various intrinsic and extrinsic factors controlling regeneration and navigation of axons within the inhibitory environment of the central nervous system. Recent advances in spinal cord research have opened new avenues for the exploration of potential targets for repairing the cord and improving functional recovery after trauma. Here, we discuss some of the important key molecules that could be harnessed for repairing spinal cord injury.

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