RESUMO
JOURNAL/nrgr/04.03/01300535-202409000-00038/figure1/v/2024-01-16T170235Z/r/image-tiff Previous studies have shown that Biochanin A, a flavonoid compound with estrogenic effects, can serve as a neuroprotective agent in the context of cerebral ischemia/reperfusion injury; however, its effect on spinal cord injury is still unclear. In this study, a rat model of spinal cord injury was established using the heavy object impact method, and the rats were then treated with Biochanin A (40 mg/kg) via intraperitoneal injection for 14 consecutive days. The results showed that Biochanin A effectively alleviated spinal cord neuronal injury and spinal cord tissue injury, reduced inflammation and oxidative stress in spinal cord neurons, and reduced apoptosis and pyroptosis. In addition, Biochanin A inhibited the expression of inflammasome-related proteins (ASC, NLRP3, and GSDMD) and the Toll-like receptor 4/nuclear factor-κB pathway, activated the Nrf2/heme oxygenase 1 signaling pathway, and increased the expression of the autophagy markers LC3 II, Beclin-1, and P62. Moreover, the therapeutic effects of Biochanin A on early post-spinal cord injury were similar to those of methylprednisolone. These findings suggest that Biochanin A protected neurons in the injured spinal cord through the Toll-like receptor 4/nuclear factor κB and Nrf2/heme oxygenase 1 signaling pathways. These findings suggest that Biochanin A can alleviate post-spinal cord injury at an early stage.
RESUMO
Postmenopausal osteoporosis is associated with bone formation inhibition mediated by the impaired osteogenic differentiation potential of bone marrow mesenchymal stem cells (BMSCs). However, identifying and confirming the essential genes in the osteogenic differentiation of BMSCs and osteoporosis remain challenging. The study aimed at revealing the key gene that regulated osteogenic differentiation of BMSCs and led to osteoporosis, thus exploring its therapeutic effect in osteoporosis. In the present study, six essential genes related to the osteogenic differentiation of BMSCs and osteoporosis were identified, namely, fibrillin 2 (Fbn2), leucine-rich repeat-containing 17 (Lrrc17), heat shock protein b7 (Hspb7), high mobility group AT-hook 1 (Hmga1), nexilin F-actin-binding protein (Nexn), and endothelial cell-specific molecule 1 (Esm1). Furthermore, the in vivo and in vitro experiments showed that Hmga1 expression was increased during the osteogenic differentiation of rat BMSCs, while Hmga1 expression was decreased in the bone tissue of ovariectomized (OVX) rats. Moreover, the expression of osteogenic differentiation-related genes, the activity of alkaline phosphatase (ALP), and the number of mineralized nodules were increased after Hmga1 overexpression, which was partially reversed by a Wnt signaling inhibitor (DKK1). In addition, after injecting Hmga1-overexpressing lentivirus into the bone marrow cavity of OVX rats, the bone loss, and osteogenic differentiation inhibition of BMSCs in OVX rats were partially reversed, while osteoclast differentiation promotion of BMSCs in OVX rats was unaffected. Taken together, the present study confirms that Hmga1 prevents OVX-induced bone loss by the Wnt signaling pathway and reveals that Hmga1 is a potential gene therapeutic target for postmenopausal osteoporosis.
Assuntos
Células-Tronco Mesenquimais , Osteoporose Pós-Menopausa , Osteoporose , Humanos , Feminino , Ratos , Animais , Osteogênese , Via de Sinalização Wnt/genética , beta Catenina/metabolismo , Osteoporose Pós-Menopausa/genética , Osteoporose Pós-Menopausa/prevenção & controle , Osteoporose Pós-Menopausa/metabolismo , Lentivirus/genética , Osteoporose/genética , Osteoporose/prevenção & controle , Osteoporose/tratamento farmacológico , Fatores de Transcrição/metabolismo , Diferenciação Celular , Células-Tronco Mesenquimais/metabolismo , Células CultivadasRESUMO
Introduction: Brachial plexus injury (BPI) is one of the most destructive peripheral nerve injuries and there is still a lack of effective treatment. Methods: This study was conducted to evaluate the effects of melatonin in the treatment of acute brachial plexus compression injury in rats using histopathological, histomorphometric, immunohistochemical and electrophysiological methods. Forty-eight adult male Sprague Dawley rats were randomly allocated into three groups: sham, melatonin and vehicle groups. The brachial plexus compression injury model was performed by a vascular clamp. Melatonin group received intraperitoneal injection of melatonin at doses of 10 mg/kg for 21 days after crush injury. The conduction velocity and amplitude of compound muscle action potential (CAMP) in the regenerated nerve, and nerve histomorphometry, as well as levels of myelin protein zero (P0) protein of the crush region were assessed. Results: Compared with the vehicle group, the melatonin group which reported significant increased CMAP conduction velocity and amplitude also showed thicker myelin sheath and lower levels of P0 protein. Discussion: Our results suggest that melatonin effectively promotes nerve regeneration and improves the function of damaged nerves. Melatonin treatment is a promising strategy for the treatment of acute brachial plexus compression injury.
RESUMO
BACKGROUND: Spinal cord injury (SCI) is a severe central nervous system trauma. The present study aimed to evaluate the effect of HIF-1α on inflammation in spinal cord injury (SCI) to uncover the molecular mechanisms of anti-inflammation. RESULTS: HIF-1α was reduced in SCI model rats and HIF-1α activation reduced TNF-α, IL-1ß, IL-6 and IL-18 levels in SCI model rats. Meanwhile, Circ 0001723 expression was down-regulated and miR-380-3p expression was up-regulated in SCI model rats. In vitro model, down-regulation of Circ 0001723 promoted TNF-α, IL-1ß, IL-6 and IL-18 levels, compared with control negative group. However, over-expression of Circ 0001723 reduced TNF-α, IL-1ß, IL-6 and IL-18 levels in vitro model. Down-regulation of Circ 0001723 suppressed HIF-1α protein expressions and induced NLRP3 and Caspase-1 protein expressions in vitro model by up-regulation of miR-380-3p. Next, inactivation of HIF-1α reduced the pro-inflammation effects of Circ 0001723 in vitro model. Then, si-NLRP3 also inhibited the pro-inflammation effects of Circ 0001723 in vitro model via promotion of autophagy. CONCLUSIONS: We concluded that HIF-1α reduced inflammation in spinal cord injury via miR-380-3p/ NLRP3 by Circ 0001723.
Assuntos
Subunidade alfa do Fator 1 Induzível por Hipóxia/metabolismo , Inflamação/metabolismo , MicroRNAs/genética , Proteína 3 que Contém Domínio de Pirina da Família NLR/metabolismo , RNA Circular/genética , Traumatismos da Medula Espinal/metabolismo , Animais , Citocinas/sangue , Regulação da Expressão Gênica , Masculino , Ratos , Ratos Sprague-DawleyRESUMO
BACKGROUND: Spinal cord injury (SCI) is a severe central nervous system trauma. The present study aimed to evaluate the effect of HIF-1α on inflammation in spinal cord injury (SCI) to uncover the molecular mechanisms of anti-inflammation. RESULTS: HIF-1α was reduced in SCI model rats and HIF-1α activation reduced TNF-α, IL-1ß, IL-6 and IL-18 levels in SCI model rats. Meanwhile, Circ 0001723 expression was down-regulated and miR-380-3p expression was up-regulated in SCI model rats. In vitro model, down-regulation of Circ 0001723 promoted TNF-α, IL-1ß, IL-6 and IL-18 levels, compared with control negative group. However, over-expression of Circ 0001723 reduced TNF-α, IL-1ß, IL-6 and IL-18 levels in vitro model. Down-regulation of Circ 0001723 suppressed HIF-1α protein expressions and induced NLRP3 and Caspase-1 protein expressions in vitro model by up-regulation of miR-380-3p. Next, inactivation of HIF-1α reduced the pro-inflammation effects of Circ 0001723 in vitro model. Then, si-NLRP3 also inhibited the pro-inflammation effects of Circ 0001723 in vitro model via promotion of autophagy. CONCLUSIONS: We concluded that HIF-1α reduced inflammation in spinal cord injury via miR-380-3p/ NLRP3 by Circ 0001723.
Assuntos
Animais , Masculino , Ratos , Traumatismos da Medula Espinal/metabolismo , MicroRNAs/genética , Subunidade alfa do Fator 1 Induzível por Hipóxia/metabolismo , Proteína 3 que Contém Domínio de Pirina da Família NLR/metabolismo , RNA Circular/genética , Inflamação/metabolismo , Regulação da Expressão Gênica , Citocinas/sangue , Ratos Sprague-DawleyRESUMO
RATIONALE: Spontaneous spinal subdural hematoma (SSDH) without an underlying pathology is a very rare condition. The treatment protocol for SSDH is early diagnosis and treatment before irreversible damage to neural tissue. However, there is no agreement on the etiopathogenesis, as well as the need for surgery to treat spontaneous SSDH. Here, we report a rare case of spontaneous SSDH with progressive deterioration and symptoms of cauda equina syndrome after ineffective conservative treatment. PATIENT'S CONCERN: A 38-year-old male patient presented with sudden lower back and bilateral leg pain. DIAGNOSIS: A magnetic resonance imaging (MRI) scan on the third day after the onset of symptoms revealed a subdural hematoma from L1 to S1, presenting as hyperintensities on T1 weighted sequences and hypointensities to isointensities on T2 weighted sequences. INTERVENTION: Laminectomy and subdural evacuation were performed immediately. OUTCOMES: An abnormal ligamentum flavum was observed intraoperatively. A histological examination revealed extravasation of blood in the degenerated ligamentum flavum. Postoperatively, the lower limb pain improved immediately. At the 6-month follow-up, the pain and numbness of the lower limb disappeared, and the muscle strength of both legs recovered completely with normal gait. LESSONS: Spontaneous SSDH with ligamentum flavum hematoma was caused by a sudden increase of intravenous pressure, resulting from a marked surge in the intra-abdominal or intrathoracic pressure. Consecutive MRI scans provided valuable information, leading to a diagnosis of spontaneous SSDH. The treatment protocol for spontaneous SSDH should be determined based on the location and stage of the hematoma, as well as the subject's neurological status.
Assuntos
Cauda Equina/patologia , Cauda Equina/cirurgia , Hematoma Subdural Espinal/complicações , Hematoma Subdural Espinal/cirurgia , Laminectomia/métodos , Adulto , Humanos , Ligamento Amarelo/patologia , Vértebras Lombares/cirurgia , Imageamento por Ressonância Magnética , Masculino , Sacro/patologiaRESUMO
To investigate the role of miR-372/Beclin-1 on nerve cell apoptosis induced by spinal cord ischemia/reperfusion injury (SCII). We established in vivo and in vitro SCII model. MiR-372 and Beclin-1 expressions in spinal cord tissues of SCII rats and SCII nerve cells were measured. The cell apoptosis was detected by flow cytometry. MiR-372 inhibitor was used to reduce miR-372 expression. Dual luciferase reporter assay was used to confirm the interaction between miR-372 and Beclin-1. MiR-372 expression in spinal cord tissues of SCII rats and SCII nerve cells was increased, while Beclin-1 expression was decreased. Knockdown of miR-372 could inhibit SCII nerve cell apoptosis. In addition, MiR-372 could negatively regulate Beclin-1 expression. Autophagy inhibitor could inhibit autophagy to promote the apoptosis of SCII nerve cells through decreasing Beclin-1, while interference of miR-372 changed the effect of autophagy inhibitor. Interference of miR-372 could reduce nerve cell apoptosis in SCII via increasing autophagy by up-regulating Beclin-1.
Assuntos
Apoptose , Autofagia , MicroRNAs/genética , Neurônios/metabolismo , Traumatismo por Reperfusão/metabolismo , Medula Espinal/metabolismo , Animais , Proteína Beclina-1/genética , Proteína Beclina-1/metabolismo , Células PC12 , Ratos , Ratos Sprague-Dawley , Traumatismo por Reperfusão/genética , Medula Espinal/irrigação sanguínea , Regulação para CimaRESUMO
Methylprednisolone exhibits anti-inflammatory antioxidant properties, and rosiglitazone acts as an anti-inflammatory and antioxidant by activating peroxisome proliferator-activated receptor-γ in the spinal cord. Methylprednisolone and rosiglitazone have been clinically used during the early stages of secondary spinal cord injury. Because of the complexity and diversity of the inflammatory process after spinal cord injury, a single drug cannot completely inhibit inflammation. Therefore, we assumed that a combination of methylprednisolone and rosiglitazone might promote recovery of neurological function after secondary spinal cord injury. In this study, rats were intraperitoneally injected with methylprednisolone (30 mg/kg) and rosiglitazone (2 mg/kg) at 1 hour after injury, and methylprednisolone (15 mg/kg) at 24 and 48 hours after injury. Rosiglitazone was then administered once every 12 hours for 7 consecutive days. Our results demonstrated that a combined treatment with methylprednisolone and rosiglitazone had a more pronounced effect on attenuation of inflammation and cell apoptosis, as well as increased functional recovery, compared with either single treatment alone, indicating that a combination better promoted recovery of neurological function after injury.
RESUMO
Kyphoplasty has been shown to provide symptomatic relief of vertebral compression fractures refractory to medical therapy. However, few reports have focused on refracture of cemented vertebrae after kyphoplasty. The presence of cemented vertebrae refracture concurrent with cement fragmentation is an extremely rare condition. We reported an 86-year-old man with a T12 osteoporotic compression fracture undergoing the kyphoplasty treatment. The patient postoperatively continued to have back pain at the same level. The solid lumped polymethylmethacrylate (PMMA) mass and inadequate use and insufficient filling of PMMA cement were observed in postoperative radiographs and magnetic resonance image (MRI) examination. He refused to receive the surgical intervention, but had not strict compliance with oral anti-osteoporotic medications. Ten months postoperatively, refracture of osteoporotic vertebral body concurrent with cement fragmentation occurred at the previously kyphoplasty-treated vertebral level. Bone mineral analysis showed severe osteoporosis with a T-score of -4.0. The patient finally obtained therapeutic benefit of pain relief and bony union of T12 vertebral body by consistently adhering to anti-osteoporotic medication treatment. This case illustrated that patients who underwent kyphoplasty to treat osteoporotic vertebral compression fractures with intravertebral fracture should be strictly followed up and supervised in their anti-osteoporotic medication treatment. The interdigitation injection pattern of PMMA and sufficient PMMA filling with trabeculae in the kyphoplasty procedure also might prevent refracture of the cemented vertebrae concurrent with PMMA fragmentation.
Assuntos
Cimentos Ósseos , Cifoplastia/métodos , Fraturas por Osteoporose/cirurgia , Fraturas da Coluna Vertebral/cirurgia , Vértebras Torácicas/lesões , Idoso de 80 Anos ou mais , Conservadores da Densidade Óssea/uso terapêutico , Fraturas por Compressão/diagnóstico por imagem , Fraturas por Compressão/cirurgia , Humanos , Masculino , Osteoporose/tratamento farmacológico , Fraturas por Osteoporose/diagnóstico por imagem , Radiografia , Recidiva , Vértebras Torácicas/diagnóstico por imagem , Vértebras Torácicas/cirurgiaRESUMO
OBJECTIVE: The aim of this retrospective investigation was to explore the influence of femoral osteoporosis on short-term curative effects of cementless hip arthroplasty and to evaluate the femoral metaphyseal bone mineral density (BMD) for femoral osteoporosis in order to guide prosthesis choice and rehabilitation. METHODS: We performed 127 total arthroplasty operations between June 1999 to February 2003 and investigated 49 cementless hip replacements with the Metalcancellous cementless Lubeck II system being used in all hips. There were twenty men and twenty-nine women whose mean age at the time of the operation was 60 years (range, 52~81 years). The patients were divided into osteoporosis or normal groups according to the femoral metaphyseal BMD measured preoperatively. The average duration of follow-up was 30 months (range, 8~52 months). We evaluated all of the patients from a clinical standpoint with use of a standard-terminology questionnaire with respect to the short-term curative effects and patients' satisfaction. Hip pain status and functional ability were important indicators of treatment efficacy. RESULTS: Harris hip score and patients' satisfaction in femoral osteoporosis patients who underwent noncemented hip arthroplasty were lower (P=0.004, P=0.03) while the incidence of thigh pain was higher (P=0.03) than the patients with non-osteoporosis. CONCLUSION: The higher incidence of pain, as well as the decrease in function experienced by the patients in osteoporosis group, supports the case that cementless arthroplasty is not a better choice for those patients and that we had better select prosthesis based on the femoral metaphyseal BMD.
Assuntos
Prótese de Quadril , Osteoporose/cirurgia , Idoso , Idoso de 80 Anos ou mais , Artroplastia de Quadril/efeitos adversos , Artroplastia de Quadril/métodos , Cimentos Ósseos , Densidade Óssea , Feminino , Fêmur/metabolismo , Fêmur/cirurgia , Necrose da Cabeça do Fêmur/metabolismo , Necrose da Cabeça do Fêmur/cirurgia , Fraturas do Quadril/metabolismo , Fraturas do Quadril/cirurgia , Prótese de Quadril/efeitos adversos , Humanos , Masculino , Pessoa de Meia-Idade , Osteoartrite/metabolismo , Osteoartrite/cirurgia , Osteoporose/metabolismo , Dor/etiologia , Dor/fisiopatologia , Estudos RetrospectivosRESUMO
OBJECTIVE: To investigate the dynamics of vascular volume and the plasma dilution of lactated Ringer's solution in patients during the induction of general and epidural anesthesia. METHODS: The hemodilution of i.v. infusion of 1000 ml of lactated Ringer's solution over 60 min was studied in patients undergoing general (n=31) and epidural (n=22) anesthesia. Heart rate, arterial blood pressure and hemoglobin (Hb) concentration were measured every 5 min during the study. Surgery was not started until the study period had been completed. RESULTS: General anesthesia caused the greater decrease of mean arterial blood pressure (MAP) (mean 15% versus 9%; P<0.01) and thereby followed by a more pronounced plasma dilution, blood volume expansion (VE) and blood volume expansion efficiency (VEE). A strong linear correlation between hemodilution and the reduction in MAP (r=-0.50; P<0.01) was found. At the end of infusion, patients undergoing general anesthesia retained 47% (SD 19%) of the infused fluid in the circulation, while epidural anesthesia retained 29% (SD 13%) (P<0.001). Correspondingly, a fewer urine output (mean 89 ml versus 156 ml; P<0.05) and extravascular expansion (454 ml versus 551 ml; P<0.05) were found during general anesthesia. CONCLUSION: We concluded that the induction of general anesthesia caused more hemodilution, volume expansion and volume expansion efficiency than epidural anesthesia, which was triggered only by the lower MAP.