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1.
Sci Rep ; 10(1): 13138, 2020 08 04.
Artigo em Inglês | MEDLINE | ID: mdl-32753675

RESUMO

Cervical spondylotic myelopathy (CSM) is caused by chronic compression of the spinal cord and is the most common cause of myelopathy in adults. No drug is currently available to mitigate CSM. Herein, we made a rat model of CSM by epidurally implanting an expanding water-absorbent polymer underneath the laminae compress the spinal cord. The CSM rats exhibited progressive motor impairments recapitulating human CSM. CSM rats had loss of spinal motor neurons, and increased lipid peroxidation in the spinal cord. Zonisamide (ZNS) is clinically used for epilepsy and Parkinson's disease. We previously reported that ZNS protected primary spinal motor neurons against oxidative stress. We thus examined the effects of ZNS on our rat CSM model. CSM rats with daily intragastric administration of 0.5% methylcellulose (n = 11) and ZNS (30 mg/kg/day) in 0.5% methylcellulose (n = 11). Oral administration of ZNS ameliorated the progression of motor impairments, spared the number of spinal motor neurons, and preserved myelination of the pyramidal tracts. In addition, ZNS increased gene expressions of cystine/glutamate exchange transporter (xCT) and metallothionein 2A in the spinal cord in CSM rats, and also in the primary astrocytes. ZNS increased the glutathione (GSH) level in the spinal motor neurons of CSM rats. ZNS potentially ameliorates loss of the spinal motor neurons and demyelination of the pyramidal tracts in patients with CSM.


Assuntos
Compressão da Medula Espinal/tratamento farmacológico , Doenças da Medula Espinal/tratamento farmacológico , Espondilose/tratamento farmacológico , Zonisamida/farmacologia , Animais , Vértebras Cervicais/metabolismo , Vértebras Cervicais/patologia , Modelos Animais de Doenças , Progressão da Doença , Feminino , Neurônios Motores/metabolismo , Neurônios Motores/patologia , Ratos , Ratos Wistar , Compressão da Medula Espinal/metabolismo , Compressão da Medula Espinal/patologia , Doenças da Medula Espinal/metabolismo , Doenças da Medula Espinal/patologia , Espondilose/metabolismo , Espondilose/patologia
3.
PLoS One ; 10(11): e0142786, 2015.
Artigo em Inglês | MEDLINE | ID: mdl-26571146

RESUMO

No clinically applicable drug is currently available to enhance neurite elongation after nerve injury. To identify a clinically applicable drug, we screened pre-approved drugs for neurite elongation in the motor neuron-like NSC34 cells. We found that zonisamide, an anti-epileptic and anti-Parkinson's disease drug, promoted neurite elongation in cultured primary motor neurons and NSC34 cells in a concentration-dependent manner. The neurite-scratch assay revealed that zonisamide enhanced neurite regeneration. Zonisamide was also protective against oxidative stress-induced cell death of primary motor neurons. Zonisamide induced mRNA expression of nerve growth factors (BDNF, NGF, and neurotrophin-4/5), and their receptors (tropomyosin receptor kinase A and B). In a mouse model of sciatic nerve autograft, intragastric administration of zonisamide for 1 week increased the size of axons distal to the transected site 3.9-fold. Zonisamide also improved the sciatic function index, a marker for motor function of hindlimbs after sciatic nerve autograft, from 6 weeks after surgery. At 8 weeks after surgery, zonisamide was protective against denervation-induced muscle degeneration in tibialis anterior, and increased gene expression of Chrne, Colq, and Rapsn, which are specifically expressed at the neuromuscular junction. We propose that zonisamide is a potential therapeutic agent for peripheral nerve injuries as well as for neuropathies due to other etiologies.


Assuntos
Isoxazóis/farmacologia , Neurônios Motores/fisiologia , Regeneração Nervosa/efeitos dos fármacos , Neuritos/fisiologia , Nervo Isquiático/fisiologia , Animais , Autoenxertos/efeitos dos fármacos , Linhagem Celular Tumoral , Células Cultivadas , Citoproteção/efeitos dos fármacos , Masculino , Camundongos Endogâmicos C57BL , Modelos Animais , Neurônios Motores/efeitos dos fármacos , Fatores de Crescimento Neural/genética , Fatores de Crescimento Neural/metabolismo , Neuritos/efeitos dos fármacos , Estresse Oxidativo/efeitos dos fármacos , RNA Mensageiro/genética , RNA Mensageiro/metabolismo , Receptores de Fator de Crescimento Neural/genética , Receptores de Fator de Crescimento Neural/metabolismo , Nervo Isquiático/efeitos dos fármacos , Fatores de Tempo , Regulação para Cima/efeitos dos fármacos , Regulação para Cima/genética , Zonisamida
4.
Spine (Phila Pa 1976) ; 40(14): E831-41, 2015 Jul 15.
Artigo em Inglês | MEDLINE | ID: mdl-25839385

RESUMO

STUDY DESIGN: Retrospective case-controlled study. OBJECTIVE: To investigate the incidence of adjacent segment degeneration (ASD) and the associated risk factors during a period of at least 10 years after posterior lumbar interbody fusion (PLIF). SUMMARY OF BACKGROUND DATA: ASD is a problematic sequelae after spinal fusion surgery. Few long-term follow-up studies have investigated ASD after PLIF; thus, magnetic resonance imaging (MRI) data available for the evaluation of postoperative changes associated with ASD are limited. METHOD: One hundred one patients were retrospectively enrolled. The minimum follow-up was 10 years after surgery. Preoperative and postoperative (2, 5, and 10 yr after surgery) Radiographs and MRI images were evaluated. Disc height, vertebral slip, and intervertebral angle were examined on radiographical images. Disc degeneration and spinal stenosis on MRI images were evaluated. Risk factors for developing early-onset radiographical ASD were evaluated using a multivariate logistic regression analysis. RESULT: The degenerative changes in disc height, vertebral slip, and intervertebral angle on radiographs 10 years after surgery were found in 12, 36, and 17 cases, respectively, at the cranial-adjacent level and in 3, 6, and 11 cases, respectively, at the caudal-adjacent level. Increased disc degeneration and spinal stenosis worsening were observed in 62 and 68 cases, respectively, at the cranial-adjacent level and in 25 and 12 cases, respectively, at the caudal-adjacent level on MRI 10 years after surgery. Ten patients (9.9%) required reoperation, and 80% of revision surgeries were performed more than 5 years after the initial surgery. High pelvic incidence was a risk factor for developing early-onset radiographical ASD. CONCLUSION: The majority of the reoperations for ASD were performed more than 5 years after the initial lumbar fusion surgery, although the progression of radiographical ASD began in the early postoperative period. A high degree of pelvic incidence was a risk factor for developing early-onset radiographical ASD. Obtaining appropriate lumbar lordosis in PLIF is important for preventing ASD. LEVEL OF EVIDENCE: 4.


Assuntos
Doenças da Coluna Vertebral/epidemiologia , Doenças da Coluna Vertebral/etiologia , Fusão Vertebral/efeitos adversos , Idoso , Estudos de Casos e Controles , Feminino , Humanos , Imageamento por Ressonância Magnética , Masculino , Pessoa de Meia-Idade , Estudos Retrospectivos , Fatores de Risco , Doenças da Coluna Vertebral/patologia , Fusão Vertebral/estatística & dados numéricos
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