Spinal Cord Injury In Rats Research Articles

Lentivirus-mediated Knockdown of Ski Improves Neurological Function After Spinal Cord Injury in Rats.

The glial scar that forms at the site of injury after spinal cord injury (SCI) is an important physical and biochemical barrier that prevents axonal regeneration and thus delays functional recovery. Ski is a multifunctional transcriptional co-regulator that is involved in a wide range of physiological and pathological processes in humans. Previous studies by our group found that Ski is significantly upregulated in the spinal cord after in vivo injury and in astrocytes after in vitro activation, suggesting that Ski may be a novel molecule regulating astrocyte activation after spinal cord injury. Further studies revealed that knockdown or overexpression intervention of Ski expression could significantly affect the proliferation and migration of activated astrocytes. To further verify the effect of knockdown of Ski expression in vivo on glial scar formation and neurological function after spinal cord injury, we prepared a rat spinal cord injury model using Allen's percussion method and used lentivirus as a vector to mediate the downregulation of Ski in the injured spinal cord. The results showed that knockdown of Ski expression after spinal cord injury significantly suppressed the expression of glial fibrillary acidic protein (Gfap) and vimentin, hallmark molecules of glial scarring, and increased the expression of neurofilament protein-200 (Nf-200) and growth-associated protein (Gap43), key molecules of axon regeneration, as well as Synaptophysin, a key molecule of synapse formation expression. In addition, knockdown of Ski after spinal cord injury also promoted the recovery of motor function. Taken together, these results suggest that Ski is able to inhibit the expression of key molecules of glial scar formation, and at the same time promotes the expression of molecules that are markers of axonal regeneration and synapse formation after spinal cord injury, making it a potential target for targeted therapy after spinal cord injury.

Resveratrol Enhances the Efficacy of Combined BM-MSCs Therapy for Rat Spinal Cord Injury via Modulation of the Sirt-1/NF-κB Signaling Pathway.

Spinal cord injury (SCI) represents a severe trauma to the central nervous system, resulting in significant disability and imposing heavy burdens on families and society. Pathophysiological changes following SCI often trigger secondary injuries that complicate treatment. Bone marrow mesenchymal stem cells (BM-MSCs) have become a focal point of research due to their multifunctionality and self-renewal capabilities; however, their survival and neuroprotective functions are compromised in inflammatory environments. Resveratrol, known for its anti-inflammatory, anti-aging, and anti-oxidative stress properties, has been extensively studied. This research focuses on the anti-inflammatory effects of resveratrol post-SCI and its combined application with BM-MSCs to treat rat spinal cord injuries, exploring both efficacy and mechanisms. In vivo experiments investigated changes in the Sirt-1 signaling pathway post-SCI, while in vitro studies examined the effects of resveratrol on BM-MSCs under inflammatory conditions. The assessment included recovery of motor function, neuronal survival, and apoptosis in SCI rats treated with resveratrol alone or in combination with BM-MSCs. Findings reveal a correlation between Sirt-1 and inflammation signaling pathways post-injury. Resveratrol significantly enhanced the survival and efficacy of BM-MSCs in inflammatory environments by upregulating Sirt-1 and downregulating NF-κB and other inflammatory markers, thereby reducing apoptosis. Combined treatment with resveratrol and BM-MSCs showed superior outcomes in motor function recovery and neuronal survival compared to treatment with BM-MSCs alone. This study offers a novel therapeutic strategy for SCI, enhancing stem cell survival and function through modulation of the Sirt-1/NF-κB pathway, providing a theoretical and experimental foundation for clinical applications.

Silencing of SH3BP2 Inhibits Microglia Activation Via the JAK/STAT Signaling in Spinal Cord Injury Models.

The purpose of our study was to investigate the expression of SH3 domain-binding protein 2 (SH3BP2) in spinal cord injury (SCI) rats and lipopolysaccharide (LPS)-induced microglia, and explored its impact as well as potential mechanism. We examined the level of SH3BP2 in SCI rats using GEO data, immunofluorescence co-staining, qRT-PCR and western blotting. Next, we constructed a rat model with SH3BP2 silencing by injecting LV-shSH3BP2 into the injury site of SCI rats, and then evaluated its neurological outcome, functional recovery, M1 polarization and neuroinflammation by Basso-Beattie-Bresnahan (BBB) score, inclined plane test, Nissl staining and hematoxylin-eosin (H&E). The SH3BP2-related signaling pathway was predicted by KEGG analysis in GSE45006 dataset. BV2 microglial cells and primary microglia were incubated with LPS, and then measured its activation and inflammation by qRT-PCR, western blotting and immunofluorescence. Further complement experiments were performed to explore the molecular mechanisms of SH3BP2. The expression of SH3BP2 was increased in the spinal dorsal horn tissues of SCI rats and LPS-induced microglia. Silencing of SH3BP2 improved neurological outcomes and functional recovery, attenuated neuroinflammation and microglia polarization in SCI rats. Additionally, the JAK/STAT pathway was regulated by SH3BP2. Silencing of SH3BP2 inhibited LPS-induced microglia inflammation and activation, decreased the phosphorylation levels of JAK and STAT. Silencing of SH3BP2 attenuated SCI by regulating the JAK/STAT pathway to inhibit the activation of microglia.

Can minor trauma cause asymptomatic cervical spinal cord compression leading to severe cervical spinal cord injury in rats?

The study aimed to determine whether asymptomatic rats with cervical spinal cord compression (CSCC) experience more severe cervical spinal cord injury (SCI) compared with rats without CSCC under the same degree of minor trauma. Four weeks after the polyvinyl alcohol-polyacrylamide hydrogel was implanted into the C5 vertebral canal, asymptomatic rats were selected based on locomotor function score. Mild cervical SCI was subsequently established based on CSCC. The motor function, morphology, neuron loss, myelin destruction, nerve cell apoptosis, microglia activation, and neuroinflammation were evaluated after SCI. Under the same injury conditions, rats in the CSCC group exhibited more severe motor dysfunction compared with those without CSCC. Similarly, asymptomatic CSCC rats showed significant damage to spinal cord tissue, neurons, and myelin. Finally, compared with rats without CSCC, asymptomatic CSCC rats experienced increased nerve cell apoptosis, microglial activation, and neuroinflammation following the same SCI. In asymptomatic CSCC rats, the same degree of minor trauma resulted in more severe cervical SCI compared with rats without CSCC. This was evidenced by increased nerve cell apoptosis, microglial activation, neuron death, myelin destruction, and a strong neuroinflammatory response, leading to severe motor dysfunction.

Neurotrophic and synaptic effects of GnRH and/or GH upon motor function after spinal cord injury in rats

Thoracic spinal cord injury (SCI) profoundly impairs motor and sensory functions, significantly reducing life quality without currently available effective treatments for neuroprotection or full functional regeneration. This study investigated the neurotrophic and synaptic recovery potential of gonadotropin-releasing hormone (GnRH) and growth hormone (GH) treatments in ovariectomized rats subjected to thoracic SCI. Employing a multidisciplinary approach, we evaluated the effects of these hormones upon gene expression of classical neurotrophins (NGF, BDNF, and NT3) as well as indicative markers of synaptic function (Nlgn1, Nxn1, SNAP25, SYP, and syntaxin-1), together with morphological assessments of myelin sheath integrity (Klüver-Barrera staining and MBP immunoreactivity) and synaptogenic proteins (PSD95, SYP) by immunohystochemistry (IHC) , and also on the neuromotor functional recovery of hindlimbs in the lesioned animals. Results demonstrated that chronic administration of GnRH and GH induced notable upregulation in the expression of several neurotrophic and synaptogenic activity genes. Additionally, the treatment showed a significant impact on the restoration of functional synaptic markers and myelin integrity. Intriguingly, while individual GnRH application induced certain recovery benefits, the combined treatment with GH appeared to inhibit neuromotor recovery, suggesting a complex interplay in hormonal regulation post-SCI. GnRH and GH are bioactive and participate in modulating neurotrophic responses and synaptic restoration under neural damage conditions, offering insights into novel therapeutic approaches for SCI. However, the intricate effects of combined hormonal treatment accentuate the necessity for further investigation that conduce to optimal and novel therapeutic strategies for patients with spinal cord lesions.

Repeated human cranial bone-derived mesenchymal stem cell transplantation improved electrophysiological recovery in a spinal cord injury rat model

Mesenchymal stem cell (MSC)-based therapy has been applied in several clinical trials of spinal cord injury (SCI). We have successfully established MSCs from human cranial bone and developed a longitudinal neuromonitoring technique for rodents. In addition to single transplantation, the potential of multiple transplantations has been suggested as a new therapeutic strategy. However, there are no reports on the electrophysiological effects of multiple MSC transplantations in SCI using transcranial electrical stimulation motor-evoked potentials (tcMEPs). Here, we aimed to elucidate the efficacy and mechanism of action of multiple MSC transplantations using tcMEPs. After establishing a weight-drop-induced SCI rat model, we performed repeated intravenous transplantation of human cranial bone-derived MSCs (hcMSCs) on days 1 and 3 post-SCI. Motor function and tcMEP recovery were evaluated 6 weeks post-transplantation. Tissue repair post-SCI was assessed using immunostaining for myelin and neurons in the injured posterior cord. Repeated hcMSC transplantation significantly improved motor function and electrophysiological recovery compared to single transplantation and control treatment. Repeated hcMSC transplantation promoted electrophysiological functional recovery by exerting a protective effect on the functional structure of pyramidal tract axons. Thus, acute-phase repeated transplantation could be a novel and effective therapeutic strategy for the clinical application of MSCs in SCI.

Biomaterial-mediated delivery of traditional Chinese medicine ingredients for spinal cord injury: a systematic review.

Biomaterials loaded with ingredients derived from traditional Chinese medicine (TCM) are viewed as a promising strategy for treating spinal cord injury (SCI). However, a comprehensive analysis of the existing literature on this topic has not yet been conducted. Therefore, this paper systematically reviews researches related to this approach, aiming to identify gaps and shortcomings in the field. PubMed, EMBASE, Web of Science, Chinese Biomedical Literature, Wanfang, and China National Knowledge Infrastructure (CNKI) were searched for retrieving studies on biomaterials loaded with TCM ingredients published from their inception to October 2024. Two reviewers performed screening of search results, information extraction, and literature quality assessment independently. For this systematic review, 41 publications were included. Six TCM ingredients-paclitaxel, curcumin, tetramethylpyrazine, resveratrol, berberine, and tanshinone IIA were combined with biomaterials for treatment of SCI. Biomaterials were categorized into hydrogels, biodegradable scaffolds, nanoparticles, and microspheres according to the type of scaffold. These drug delivery systems exhibit commendable biocompatibility, drug-loading capacity, and drug-release capabilities, and in combination with TCM ingredients, synergistically contribute to anti-oxidative stress, anti-inflammatory, neuroprotective, and anti-apoptotic effects. These studies demonstrated the efficacy of biomaterials loaded with TCM ingredients in facilitating motor function recovery and neuroprotection in SCI rats, providing evidence for future research. However, in the complex microenvironment of SCI, achieving the maximum drug loading capacity of TCM ingredients within biomaterials, along with sustained and controlled release to fully exert their pharmacological effects, remains a major challenge for future research. https://www.crd.york.ac.uk/PROSPERO/ identifier CRD42024505000.

Human Amniotic Epithelial Stem Cells Promote Functional Recovery After Spinal Cord Injury In Rats By Regulating The Polarization Of Macrophages.

Spinal cord injury (SCI) is a catastrophic nerve injury caused by extremelysevere damage to thespinalcord, for which effective treatments are currently unavailable. Human amniotic epithelial stem cells (hAESCs) are considered promising candidates for transplantation in various clinical and preclinical applications, due to their lack of limitations such as ethical barriers, immune rejection, tumorigenicity, or cell origin. Nevertheless, the effectiveness and mechanism by which hAESCs treat SCI remain elusive.To assess the motor function recovery process following SCI in rats, the Basso Beattie Bresnahan (BBB) behavior test, inclined plate scale and motor evoked potential (MEP) analysis were used in this study after transplantation of hAESCs at different doses. And the underlying mechanism was investigated by histological and molecular methods. The transplantation of hAESCs can significantly promote the recovery of motor function in SCI group, and the higher the dose, the better the effect. Compared with SCI group, hAESCs group had reduced tissue damage, significantly increased the number of neurons, neurofilaments and myelin sheath, and significantly reduced syringomyelia and glial scars. In addition, hAESCs inhibited the Levels of tumor necrosis factor (TNF-α) and interleukin-6 (IL-6) and increased the expression of the interleukin-4 (IL-4), interleukin-10 (IL-10) and interleukin-13 (IL-13), and promoted the shift of M1-polarized macrophages to M2-polarized macrophages. Our results demonstrate that hAESCs promoted the recovery of motor function after SCI by promoting M2 polarization of macrophages and reducing neuroinflammation.These findings may provide novel therapeutic strategies for SCI.

Low-Energy extracorporeal shockwave therapy improves locomotor functions, tissue regeneration and modulating the inflammation induced FGF1 and FGF2 signaling to protect damaged tissue in spinal cord injury of rat model: An experimental animal study.

Spinal cord injury (SCI) is a debilitating condition that results in severe motor function impairments. Current therapeutic options remain limited, underscoring the need for novel treatments. Extracorporeal shockwave therapy (ESWT) has emerged as a promising noninvasive approach for treating musculoskeletal disorders and nerve regeneration. This study explored the effects of low-energy ESWT on locomotor function, tissue regeneration, inflammation, and mitochondrial function in a rat SCI model. Experiments were performed using locomotor function assays, CatWalk gait analysis, histopathological examination, immunohistochemical and immunofluorescence staining. The findings demonstrated that low-energy ESWT had a dose-dependent effect, with three treatment sessions (ESWT3) showing superior outcomes compared to a single session. ESWT3 significantly improved motor functions (run patterns, run average speed, and maximum variation, as well as the Basso, Beattie, and Bresnahan (BBB) score) and promoted tissue regeneration while reducing inflammation. ESWT3 significantly decreased levels of IL-1β, IL6 and macrophages (CD68) while increasing leucocyte (CD45) infiltration. Additionally, ESWT3 upregulated NueN and mitofusin 2 (MFN2), suggesting enhanced neuronal health and mitochondrial function. Moreover, ESWT3 modulated the expression of fibroblast growth factor 1 (FGF1), FGF2, their receptor FGFR1 and phosphorylation of ERK, aiding tissue repair and regeneration in SCI. This study highlights the potential of low-energy ESWT as an effective noninvasive treatment for SCI, demonstrating significant improvements in motor recovery, tissue regeneration, anti-inflammatory effects, and mitochondrial protection. These findings provide valuable insights into the mechanisms of ESWT and its therapeutic application for SCI recovery.

Ketone Esters Partially and Selectively Rescue Mitochondrial Bioenergetics After Acute Cervical Spinal Cord Injury in Rats: A Time-Course.

Spinal cord injury (SCI) pathology and pathophysiology can be attributed to both primary physical injury and secondary injury cascades. Secondary injury cascades involve dysregulated metabolism and energetic deficits directly linked to compromised mitochondrial bioenergetics. Rescuing mitochondrial function and reducing oxidative stress are associated with neuroprotection. In this regard, ketosis after traumatic brain injury (TBI), or after SCI, improves secondary neuropathology by decreasing oxidative stress, increasing antioxidants, reducing inflammation, and improving mitochondrial bioenergetics. Here, we follow up on our previous study and have used an exogenous ketone monoester, (R)-3-hydroxybutyl (R)-3-hydroxybutyrate (KE), as an alternative to a ketogenic diet, focusing on mitochondrial function between 1 and 14 days after injury. Starting 3 h following a cervical level 5 (C5) hemi-contusion injury, animals were fed either a standard control diet (SD) or a ketone ester diet (KED) combined with KE administered orally (OKE). We found that mitochondrial function was reduced after SCI at all times post-SCI, accompanied by reduced expression of most of the components of the electron transport chain (ETC). The KE rescued some of the bioenergetic parameters 1 day after SCI when D-β-Hydroxybutyrate (BHB) concentrations were ~2 mM. Still, most of the beneficial effects were observed 14 days after injury, with BHB concentrations reaching values of 4-6 mM. To our knowledge, this is the first report to show the beneficial effects of KE in rescuing mitochondrial function after SCI and demonstrates the suitability of KE in ameliorating the metabolic dysregulation that occurs after traumatic SCI without requiring a restrictive dietary regime.

Effectiveness of Insolubilized Poly(vinyl alcohol)-Based Electrospun Fiber-Loaded Methylprednisolone by Enzyme-Catalyzed Cross-Linking in a Rat Spinal Cord Injury Model.

Spinal cord injury (SCI) has been implicated in neural loss and, consequently, motor/sensory impairment. Here, we propose an improved formation for fibrous mat fabrication from the derivatives of poly(vinyl alcohol) (PVA) and gelatin (Gela) through horseradish peroxidase-mediated cross-linking, providing a sustained release of methylprednisolone (MP) for SCI repair. After 28 days, the animals were evaluated in terms of remyelination and apoptosis and underwent behavioral tests. The mechanical properties, hydrophobicity, and degradation rate of PVAPh/GelaPh fibrous mats were significantly improved as compared with those of PVAPh samples. This could provide the desired structure for a sustained MP release. The seeded cells could adhere and proliferate to the composite fibers, which indicates the cytocompatibility of the resultant PVAPh/GelaPh fibrous mat. The results showed significant reductions in the number of apoptotic neurons and a substantial improvement in remyelination in the SCI+ PVAPh/GelaPh + MP group. The behavioral tests confirmed improvement in locomotor hindlimb function following treatment. The MP-loaded PVAPh/GelaPh mat developed through the long-term release of MP and the biocompatible fabricated mat could inhibit axonal demyelination, attenuate apoptosis, and improve the functional outcome, which verified the potential of PVAPh/GelaPh + MP nanocomposites as a bioactive scaffold for SCI regeneration.

Anti-oxidant, anti-apoptotic and anti-inflammatory effects of geraniin in spinal cord injury in rat: role of COX-2.

Spinal cord injury (SCI) is devastating diseases affecting the degeneration of the spinal column, and vascular problems. However, the currently available therapeutic interventions are insufficient to address the effect of SCI which leads to significant impact on the morbidity and mortality of patients. In the present manuscript, we intend to investigate the pharmacological effect of geraniin on the SCI in Sprague-Dawley (SD) rats. The SCI in rats were induced by the conventional weight-drop method and treated with GER (2.5, 5, and 10 mg/kg). Subsequently, the locomotor activity of rats with SCI was assessed using Basso, Beattie, and Bresnahan (BBB) scores, while oxidative stress indicators and inflammatory variables were analyzed using commercially available kits. Additionally, neuronal death was quantified using TUNEL labeling. The enzymatic activity of caspase 3, 8, and 9 was also assessed. Furthermore, the expression levels of Bcl2, Bax, and COX-2 in rat spinal cords after SCI were analyzed by RT-PCR analysis. Our research indicated that therapy with GER in a manner that depends on the dosage could enhance the functional recovery, as well as reduce the occurrence of apoptosis, mitigate the inflammatory and oxidative response in rats with SCI. Furthermore, it was observed that GER increased the expression of Bcl2 and decreased the expression of Bax and COX-2. The concentration of caspase-3, -8, and -9 was observed to be decreased in SCI rats treated with GER. GER might protect the spinal cord from SCI by reducing apoptosis, oxidative stress, and inflammatory response through the inhibition of COX-2.

Icariin promotes functional recovery in rats after spinal cord injury by inhibiting YAP and regulating PPM1B ubiquitination to inhibiting the activation of reactive astrocytes.

The limited ability to regenerate axons after spinal cord injury (SCI) is influenced by factors such as astrocyte activation, reactive proliferation, and glial scar formation. The TGF-β/Smad (transforming growth factor-β/mothers against decapentaplegic homolog) pathway, associated with astrocytic scarring, plays a crucial role in recovery post-injury. This study aims to investigate how icariin (ICA) interacts with reactive astrocytes in the treatment of spinal cord injury. A rat SCI model was constructed, and the recovery of motor function was observed after treatment with ICA.HE staining, LFB staining, immunofluorescence staining, and Western blotting were employed to assess ICA's ability to inhibit astrocyte proliferation in rats following spinal cord injury by modulating YAP, as well as to evaluate the reparative effects of ICA on the injured spinal cord tissue. Primary astrocytes were isolated and cultured. Immunoprecipitation-Western Blot (IP-WB) ubiquitination and cytoplasm-nuclear separation were employed to assess PPM1B ubiquitination and nuclear translocation. The CatWalk XT gait analysis, BBB (Basso, Beattie, and Bresnahan) score, electrophysiological measurements, HE staining, and LFB staining collectively demonstrated that ICA promotes motor function and tissue recovery following spinal cord injury in rats. Immunofluorescence staining and Western Blot analyses revealed that ICA inhibits astrocyte proliferation in rats post-spinal cord injury by suppressing YAP activity. Furthermore, the activation of YAP by XMU-MP-1 was shown to compromise the efficacy of ICA in these rats after spinal cord injury. Additional immunofluorescence staining and Western Blot experiments confirmed that ICA inhibits TGFβ1-induced astrocyte activation through the regulation of YAP. The knockdown of PPM1B (protein phosphatase, Mg2+/Mn2+-dependent 1B) in astrocytes was found to inhibit TGFβ signaling. Additionally, YAP was shown to regulate PPM1B ubiquitination and nuclear translocation through immunoprecipitation-Western blot analysis, along with the segregation of cytoplasm and nucleus. Icariin promotes functional recovery in rats after spinal cord injury by inhibiting YAP and regulating PPM1B ubiquitination to inhibiting the activation of reactive astrocytes.

KDM2B and its peptides promote the stem cells from apical papilla mediated nerve injury repair in rats by intervening EZH2 function.

How to improve the neurogenic potential of mesenchymal stem cells (MSCs) and develop biological agent based on the underlying epigenetic mechanism remains a challenge. Here, we investigated the effect of histone demethylase Lysine (K)-specific demethylase 2B (KDM2B) on neurogenic differentiation and nerve injury repair by using MSCs from dental apical papilla (SCAP). We found that KDM2B promoted the neurogenic indicators expression and neural spheres formation in SCAP, and modified the Histone H3K4 trimethylation (H3K4me3) methylation on neurogenesis-related genes. KDM2B improved the SCAP mediated recovery of motor ability at the early healing stage of spinal cord injury rats. Meanwhile, KDM2B acted as a negative regulator to its partner EZH2 during neurogenic differentiation, enhancer of zeste homologue 2 (EZH2) suppressed the neurogenic ability of SCAP. Further, the protein interaction between KDM2B and EZH2 was identified which decreased during neurogenic differentiation. On this basis, we revealed seven key protein binding sequences of KDM2B to EZH2, and synthesized KDM2B-peptides based on these sequences. By the usage of KDM2B-peptides, EZH2 function was effectively intervened and the neurogenic ability of SCAP was promoted. More, KDM2B-peptides significantly improved the SCAP mediated functional recovery at SCI early phase. Our study revealed that KDM2B acted as a promotor to neurogenic differentiation ability of dental MSCs through binding and negatively regulating EZH2, and provided the KDM2B-peptides as candidate agents for improving the neurogenic ability of MSCs and nerve injury repair.

No impact of anti-inflammatory medication on inflammation-driven recovery following cervical spinal cord injury in rats

Following spinal cord injury (SCI), inflammation is associated with the exacerbation of damage to spinal tissue. Consequently, managing inflammation during the acute and subacute phases is a common target in SCI treatment. However, inflammation may also induce potential benefits, including the stimulation of neuroplasticity and repair. This positive role of inflammation in spinal cord healing and functional recovery is not fully understood. To address this knowledge gap, we examined the effects of two common anti-inflammatory medications, Diphenhydramine and Methylprednisolone, on the efficacy of rehabilitative motor training on recovery from subacute cervical SCI in adult rats. Training depends critically on neuroplasticity thus if inflammation is a key regulator, we propose that anti-inflammatory drugs will reduce subsequent recovery. Both drugs were administered orally over one month, alongside task-specific reaching and grasping training.After treatment, no substantial changes in motor recovery or lesion size between the treated and control groups were observed. Treated animals also did not show any discernible changes in sensory function or anxiety-like behavior. Taken together, our data indicate that the prolonged use of these anti-inflammatory agents at commonly used doses did not profoundly impact recovery following an SCI. Therefore, considering earlier reports of the benefits of pro-inflammatory stimuli on plasticity, further studies in this area are imperative to elucidate the true impact of treating inflammation and its implications for recovery after spinal cord injuries.

Novel 3D bioprinting approach for spinal cord injury repair using neural stem cells and TGF-β1 monoclonal antibody

ObjectiveTo investigate the repair of spinal cord injury (SCI) in rats using 3D bioprinted decellularized extracellular matrix (dECM) hydrogel, neural stem cells (NSCs), and TGF-β1 monoclonal antibody. MethodsThe spinal cord-derived dECM hydrogel (SC-dECM-gel) was optimized for 3D printing. Rheological tests established a 3 ​% concentration as optimal. In vitro tests assessed the effects of TGF-β1 monoclonal antibody on NSC viability and differentiation. A rat SCI model was treated with the printed gel, and recovery was monitored using the Basso-Beattie-Bresnahan test and evoked potentials. ResultsThe 3 ​% SC-dECM-gel showed superior rheological properties. TGF-β1 monoclonal antibody enhanced NSC survival and differentiation in vitro. In vivo, the 3D bioprinted gel significantly improved motor function and promoted neuronal regeneration. Conclusion3D bioprinted SC-dECM-gel loaded with NSCs and TGF-β1 monoclonal antibody effectively restores motor function and promotes regeneration in SCI rats, offering a promising approach for SCI treatment.

Photobiomodulation reduces spinal cord edema by decreasing the expression of AQP4 in the astrocytes of male spinal cord injury rats via the JAK2/STAT3 signaling pathway.

BackgroundSpinal cord swelling commonly occurs following SCI. Previous studies suggest that PBM may reduce inflammation and scar formation after SCI. However, whether PBM can alleviate post-spinal cord injury edema and its underlying mechanisms have not yet been reported. This study aims to investigate the effects of PBM on spinal cord swelling in rats following SCI and explore the underlying mechanisms. MethodsA rat model of SCI was established, and the rats received continuous PBM therapy for two weeks. Tissue hydration, motor function, AQP4 expression, and pathological changes in the spinal cord were evaluated at different time points. In vitro, astrocytes were subjected to PBM and treated with either cucurbitacin I or TGN020 following OGD. ResultsThe results indicate that PBM reduces tissue swelling in rats with SCI, improves motor function recovery, and inhibits the upregulation of AQP4 and GFAP associated with SCI. In vitro, PBM reduces abnormal activation of the JAK2/STAT3 signaling pathway in astrocytes, leading to decreased AQP4 synthesis and astrocyte activation. ConclusionsThese findings suggest that PBM reduces spinal cord swelling in rats after injury. This effect is associated with the inhibition of JAK2/STAT3 signaling pathway activation in astrocytes and the reduction in AQP4 expression.

Berberine attenuates neuronal ferroptosis via the AMPK–NRF2–HO-1-signaling pathway in spinal cord-injured rats

Ferroptosis, characterized by iron-dependent accumulation of lipid peroxides, plays an important role in spinal cord injury (SCI). Berberine (BBR), as a lipid peroxide scavenger, has been widely used in treating other diseases; however, its role in ferroptosis has not been fully elucidated. Therefore, here, to test our hypothesis that BBR can reduce the severity of SCI and promote motor function recovery by inhibiting neuronal ferroptosis, we evaluated the changes in ferroptosis-related indicators after BBR administration by establishing a cellular ferroptosis model and an SCI contusion model. We found that BBR administration significantly reduces lipid peroxidation damage, maintains normal mitochondrial function, reduces excessive accumulation of iron ions, enhances antioxidant capacity, and activates the ferroptosis defense system in vivo and in vitro. Mechanistically, BBR alleviates neuronal ferroptosis by inducing adenosine monophosphate-activated protein kinase (AMPK) phosphorylation and up-regulating nuclear factor erythroid 2-related factor 2 (NRF2) and heme oxygenase-1 (HO-1) protein expression to promote glutathione production. BBR administration also significantly improves motor function recovery in SCI rats. Meanwhile, applying the AMPK inhibitor Compound C blocks the neuroprotective and all other effects of BBR. Collectively, our findings demonstrate that BBR can attenuate neuronal ferroptosis after SCI by activating the AMPK–NRF2–HO-1 pathway.

Preventive Effects of Gonadotropin-Releasing Hormone Treatment on Urinary Bladder and Kidney Damage in Spinal Cord Injured Rats.

One of the main causes of a neurogenic bladder is spinal cord injury (SCI),(SCI), which induces little or no bladder reflex activity. Because of this alteration, there is an increased risk of developing urinary tract infections and kidney damage. Gonadotropin-releasing hormone (GnRH) treatment has been shown to improve micturition in a rat model of SCI. The present study was aimed at determining whether GnRH administration is capable to reduce bladder and kidney damage in rats with SCI. Ovariectomized female Wistar rats were divided into three groups: sham, SCI with saline solution (SCI), and SCI treated with GnRH (SCI+GnRH) for 6 weeks. SCI was induced by compression at the T10 spinal level. At the end of the experiment, bladders and kidneys were processed for morphological and immunofluorescence analysis. For morphometric analysis, the thickness of the urothelium and the muscular layer of the bladder was measured, as well as the intensity of staining related to collagen in the kidney. At the end of the experiment, all animals in the sham group showed normal urination (100%), in contrast, the percentage of untreated injured rats (SCI) that did not require manual stimulation for micturition was 19%, while the treated group (SCI+GnRH) was 68%. A significative increase in bladder weight, urothelial and muscle thickness, and collagen-related coloration in the kidney was observed in SCI when compared to sham rats. GnRH administration decreased damage to the urinary bladder and kidneys after SCI in rats. These results suggest that this hormone could be a potential preventive treatment for SCI patients at risk of neurogenic bladder and kidney damage. Not applicable.

Depression-like behavior is associated with deficits in cognition and hippocampal neurogenesis in a subset of spinally contused male, but not female, rats

Depression and cognitive deficits present at higher rates among people with spinal cord injury (SCI) compared to the general population, yet these SCI comorbidities are poorly addressed. Sex and age appear to play roles in depression incidence, but consensus on the direction of their effects is limited. Systemic and cortical inflammation and disruptions in hippocampal neurogenesis have been identified as potential treatment targets, but a comprehensive understanding of these mechanisms remains elusive.We used a rodent SCI model to interrogate these gaps in knowledge. We examined post-injury depression-like behavior and cognitive deficits, as well as the association between affect, cognition, chronic hippocampal inflammation and hippocampal neurogenesis, in young and middle-aged male and female Sprague-Dawley rats. Depression-like behavior manifested in male and female subsets of SCI rats irrespective of age, at rates commensurate with the incidence of clinical depression. Changes in components of behavior were driven by sex and age, and affective outcomes were independent of common post-injury pathophysiological outcomes including locomotor functional deficits and spinal lesion severity. Interestingly, however, only male depression-like SCI rats exhibited deficits in hippocampal-associated spatial cognition. Neurogenesis was also disrupted in only SCI males in regions of the hippocampus responsible for affective outcomes. Decreased neurogenesis among middle-aged male subjects coincided with increases in numbers of the pro-inflammatory markers CD86 and iNOS, while middle-aged females had increased numbers of cells expressing Iba-1 and anti-inflammatory marker CD206.Overall, the present data suggest that post-SCI depression and cognition may be affected, in part, by sex- and age-dependent changes in hippocampal neurogenesis and inflammation. Hippocampal neurogenesis is a potential target to address psychological wellbeing after SCI, but therapeutic strategies must carefully consider sex and age as biological variables.