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1.
Int J Mol Sci ; 19(2)2018 Feb 08.
Artigo em Inglês | MEDLINE | ID: mdl-29419747

RESUMO

BACKGROUND: Parkinson's disease (PD) is typically characterized by impairment of motor function. Gait disturbances similar to those observed in patients with PD can be observed in animals after injection of neurotoxin 6-hydroxydopamine (6-OHDA) to induce unilateral nigrostriatal dopamine depletion. Exercise has been shown to be a promising non-pharmacological approach to reduce the risk of neurodegenerative disease. METHODS: In this study, we investigated the long-term effects of voluntary running wheel exercise on gait phenotypes, depression, cognitive, rotational behaviors as well as histology in a 6-OHDA-lesioned rat model of PD. RESULTS: We observed that, when compared with the non-exercise controls, five-week voluntary exercise alleviated and postponed the 6-OHDA-induced gait deficits, including a significantly improved walking speed, step/stride length, base of support and print length. In addition, we found that the non-motor functions, such as novel object recognition and forced swim test, were also ameliorated by voluntary exercise. However, the rotational behavior of the exercise group did not show significant differences when compared with the non-exercise group. CONCLUSIONS: We first analyzed the detailed spatiotemporal changes of gait pattern to investigate the potential benefits after long-term exercise in the rat model of PD, which could be useful for future objective assessment of locomotor function in PD or other neurological animal models. Furthermore, these results suggest that short-term voluntary exercise is sufficient to alleviate cognition deficits and depressive behavior in 6-OHDA lesioned rats and long-term treatment reduces the progression of motor symptoms and elevates tyrosine hydroxylase (TH), Brain-derived neurotrophic factor (BDNF), bone marrow tyrosine kinase in chromosome X (BMX) protein expression level without affecting dopaminergic (DA) neuron loss in this PD rat model.


Assuntos
Cognição , Atividade Motora , Doença de Parkinson/fisiopatologia , Doença de Parkinson/psicologia , Esforço Físico , Animais , Comportamento Animal , Fator Neurotrófico Derivado do Encéfalo/metabolismo , Modelos Animais de Doenças , Dopamina/metabolismo , Neurônios Dopaminérgicos/metabolismo , Feminino , Marcha , Neuroproteção , Oxidopamina/efeitos adversos , Doença de Parkinson/etiologia , Doença de Parkinson/terapia , Proteínas Tirosina Quinases/genética , Proteínas Tirosina Quinases/metabolismo , Ratos , Substância Negra , Tirosina 3-Mono-Oxigenase/metabolismo
2.
Int J Mol Sci ; 19(4)2018 Apr 11.
Artigo em Inglês | MEDLINE | ID: mdl-29641447

RESUMO

In the present study, the effectiveness of glucose-dependent insulinotropic polypeptide (GIP) was evaluated by behavioral tests in 6-hydroxydopamine (6-OHDA) hemi-parkinsonian (PD) rats. Pharmacokinetic measurements of GIP were carried out at the same dose studied behaviorally, as well as at a lower dose used previously. GIP was delivered by subcutaneous administration (s.c.) using implanted ALZET micro-osmotic pumps. After two days of pre-treatment, male Sprague Dawley rats received a single unilateral injection of 6-OHDA into the medial forebrain bundle (MFB). The neuroprotective effects of GIP were evaluated by apomorphine-induced contralateral rotations, as well as by locomotor and anxiety-like behaviors in open-field tests. Concentrations of human active and total GIP were measured in plasma during a five-day treatment period by ELISA and were found to be within a clinically translatable range. GIP pretreatment reduced behavioral abnormalities induced by the unilateral nigrostriatal dopamine (DA) lesion produced by 6-OHDA, and thus may be a novel target for PD therapeutic development.


Assuntos
Antiparkinsonianos/uso terapêutico , Incretinas/uso terapêutico , Transtornos Parkinsonianos/tratamento farmacológico , Animais , Antiparkinsonianos/administração & dosagem , Incretinas/administração & dosagem , Locomoção , Masculino , Oxidopamina/toxicidade , Transtornos Parkinsonianos/etiologia , Ratos , Ratos Sprague-Dawley
3.
BMJ Open Qual ; 12(1)2023 01.
Artigo em Inglês | MEDLINE | ID: mdl-36690383

RESUMO

INTRODUCTION: Soreness is a common complaint in patients who receive lumbar spine surgery (LSS) for degenerative lumbar spine diseases (DLSD). However, soreness is not assessed independently and its impacts on outcomes of LSS remains largely unknown. Sng(pronounced sә-ng, ) in Chinese language is the word with the closest meaning to soreness, and Chinese-speaking people naturally use sng to describe their non-pain 'soreness' symptom. This study was aimed to investigate the prevalence and impacts of soreness or sng on outcome of LSS by introducing Visual Analogue Scale (VAS) of sng on back and leg. MATERIALS AND METHODS: This prospective cohort study recruited patients who receive LSS for DLSD. Participants completed the patient-reported outcome measures at 1 week before and 1 years after LSS. The patient-reported outcome measures included (1) VAS for back pain, leg pain, back sng and leg sng, (2) Oswestry Disability Index (ODI) and (3) RAND 36-item Short Form Health Survey. The minimal clinical important difference (MCID) of ODI and physical component health-related quality of life (HRQoL) was used. RESULTS: A total of 258 consecutive patients were included and 50 dropped out at follow-up. Preoperatively, the prevalence of sng was comparable to pain both on back and leg; postoperatively, the prevalence of sng was higher than pain. Leg and back sng were associated with preoperative and postoperative mental HRQoL, respectively. The reduction of sng on back and leg were significantly less than pain postoperatively. Leg sng was the only symptom independently associated with attaining MCID. CONCLUSION: Soreness or sng should be assessed independently from pain in patients receiving LSS for DLSD because soreness or sng had substantial clinical impacts on the outcome of LSS.


Assuntos
Dor nas Costas , Qualidade de Vida , Humanos , Estudos Prospectivos , Dor nas Costas/etiologia , Medição da Dor , Perna (Membro)
4.
Cells ; 10(5)2021 04 23.
Artigo em Inglês | MEDLINE | ID: mdl-33922541

RESUMO

The mechanism of pain chronicity is largely unknown in lumbar radiculopathy (LR). The anatomical location of nerve injury is one of the important factors associated with pain chronicity of LR. Accumulating evidence has shown constriction distal to the dorsal root ganglion (DRG) caused more severe radiculopathy than constriction proximal to the DRG; thereby, the mechanism of pain chronicity in LR could be revealed by comparing the differences in pathological changes of DRGs between nerve constriction distal and proximal to the DRG. Here, we used 2 rat models of LR with nerve constriction distal or proximal to the DRG to probe how the different nerve injury sites could differentially affect pain chronicity and the pathological changes of DRG neuron subpopulations. As expected, rats with nerve constriction distal to the DRG showed more persistent pain behaviors than those with nerve constriction proximal to the DRG in 50% paw withdraw threshold, weight-bearing test, and acetone test. One day after the operation, distal and proximal nerve constriction showed differential pathological changes of DRG. The ratios of activating transcription factor3 (ATF3)-positive DRG neurons were significantly higher in rats with nerve constriction distal to DRG than those with nerve constriction proximal to DRG. In subpopulation analysis, the ratios of ATF3-immunoreactivity (IR) in neurofilament heavy chain (NFH)-positive DRG neurons significantly increased in distal nerve constriction compared to proximal nerve constriction; although, both distal and proximal nerve constriction presented increased ratios of ATF3-IR in calcitonin gene-related peptide (CGRP)-positive DRG neurons. Moreover, the nerve constriction proximal to DRG caused more hypoxia than did that distal to DRG. Together, ATF3 expression in NHF-positive DRG neurons at the acute stage is a potential bio-signature of persistent pain in rat models of LR.


Assuntos
Fator 3 Ativador da Transcrição/metabolismo , Gânglios Espinais/patologia , Região Lombossacral/patologia , Neurônios Aferentes/patologia , Dor/diagnóstico , Radiculopatia/complicações , Células Receptoras Sensoriais/patologia , Fator 3 Ativador da Transcrição/genética , Animais , Gânglios Espinais/lesões , Gânglios Espinais/metabolismo , Masculino , Neurônios Aferentes/metabolismo , Dor/etiologia , Dor/metabolismo , Ratos , Ratos Sprague-Dawley , Células Receptoras Sensoriais/metabolismo
5.
J Neurotrauma ; 33(22): 2044-2054, 2016 11 15.
Artigo em Inglês | MEDLINE | ID: mdl-26972789

RESUMO

Mild traumatic brain injury (mTBI) is a major public health issue, representing 75-90% of all cases of TBI. In clinical settings, mTBI, which is defined as a Glascow Coma Scale (GCS) score of 13-15, can lead to various physical, cognitive, emotional, and psychological-related symptoms. To date, there are no pharmaceutical-based therapies to manage the development of the pathological deficits associated with mTBI. In this study, the neurotrophic and neuroprotective properties of glucose-dependent insulinotropic polypeptide (GIP), an incretin similar to glucagon-like peptide-1 (GLP-1), was investigated after its steady-state subcutaneous administration, focusing on behavior after mTBI in an in vivo animal model. The mTBI rat model was generated by a mild controlled cortical impact (mCCI) and used to evaluate the therapeutic potential of GIP. We used the Morris water maze and novel object recognition tests, which are tasks for spatial and recognition memory, respectively, to identify the putative therapeutic effects of GIP on cognitive function. Further, beam walking and the adhesive removal tests were used to evaluate locomotor activity and somatosensory functions in rats with and without GIP administration after mCCI lesion. Lastly, we used immunohistochemical (IHC) staining and Western blot analyses to evaluate the inflammatory markers, glial fibrillary acidic protein (GFAP), amyloid-ß precursor protein (APP), and bone marrow tyrosine kinase gene in chromosome X (BMX) in animals with mTBI. GIP was well tolerated and ameliorated mTBI-induced memory impairments, poor balance, and sensorimotor deficits after initiation in the post-injury period. In addition, GIP mitigated mTBI-induced neuroinflammatory changes on GFAP, APP, and BMX protein levels. These findings suggest GIP has significant benefits in managing mTBI-related symptoms and represents a novel strategy for mTBI treatment.


Assuntos
Concussão Encefálica/tratamento farmacológico , Disfunção Cognitiva/tratamento farmacológico , Polipeptídeo Inibidor Gástrico/administração & dosagem , Mediadores da Inflamação/antagonistas & inibidores , Desempenho Psicomotor/efeitos dos fármacos , Animais , Concussão Encefálica/metabolismo , Concussão Encefálica/psicologia , Disfunção Cognitiva/metabolismo , Disfunção Cognitiva/psicologia , Humanos , Inflamação/tratamento farmacológico , Inflamação/metabolismo , Inflamação/psicologia , Mediadores da Inflamação/metabolismo , Injeções Subcutâneas , Masculino , Desempenho Psicomotor/fisiologia , Ratos , Ratos Sprague-Dawley
6.
PLoS One ; 7(6): e39226, 2012.
Artigo em Inglês | MEDLINE | ID: mdl-22723969

RESUMO

BACKGROUND: Much recent research effort in traumatic brain injury (TBI) has been devoted to the discovery of a reliable biomarker correlating with severity of injury. Currently, no consensus has been reached regarding a representative marker for traumatic brain injury. In this study, we explored the potential of epithelial/endothelial tyrosine kinase (Etk) as a novel marker for TBI. METHODOLOGY/PRINCIPAL FINDINGS: TBI was induced in Sprague Dawley (SD) rats by controlled cortical impact. Brain tissue samples were analyzed by Western blot, Q-PCR, and immunofluorescence staining using various markers including glial fibrillary acidic protein, and epithelial/endothelial tyrosine kinase (Etk). Results show increased Etk expression with increased number and severity of impacts. Expression increased 2.36 to 7-fold relative to trauma severity. Significant upregulation of Etk appeared at 1 hour after injury. The expression level of Etk was inversely correlated with distance from injury site. Etk and trauma/inflammation related markers increased post-TBI, while other tyrosine kinases did not. CONCLUSION/SIGNIFICANCE: The observed correlation between Etk level and the number of impacts, the severity of impact, and the time course after impact, as well as its inverse correlation with distance away from injury site, support the potential of Etk as a possible indicator of trauma severity.


Assuntos
Lesões Encefálicas/genética , Regulação da Expressão Gênica , Neurônios/metabolismo , Proteínas Tirosina Quinases/genética , Animais , Encéfalo/metabolismo , Encéfalo/patologia , Lesões Encefálicas/metabolismo , Modelos Animais de Doenças , Masculino , Proteínas do Tecido Nervoso/genética , Proteínas do Tecido Nervoso/metabolismo , Proteínas Tirosina Quinases/metabolismo , Ratos , Ratos Sprague-Dawley , Proteínas S100/genética , Proteínas S100/metabolismo , Índices de Gravidade do Trauma
8.
Xi Bao Yu Fen Zi Mian Yi Xue Za Zhi ; 19(4): 393-4, 2003 Jul.
Artigo em Chinês | MEDLINE | ID: mdl-15163395

RESUMO

AIM: To prepare mAb against bovine bFGF and identify their Ig subgroups so as to establish an ELISA for detection of bFGF level. METHODS: BALB/c mice were immunized by recombinant bovine bFGF. Hybridoma cell lines which could stably secret the monoclonal antibodies to bFGF were established by cell fusion technique, and their related characteristics were identified. In addition, polyclonal antibodies to bFGF were prepared by immunization of rabbits with bovine bFGF. The mAb and polyclonal antibodies purified through protein A affinity chromatography were used to develop a sandwich ELISA for detection of bFGF level. RESULTS: Three hybridoma cell lines which could secret the mAbs IgG 1 to bFGF were obtained. The concentration of bFGF could be detected by sandwich ELISA developed with purified mAb and polyclonal antibody at nanogram level. CONCLUSION: mAb and polyclonal antibodies against to bovine bFGF have been prepared successfully, which provide powerful tool for further clinical application and related studies.


Assuntos
Anticorpos Monoclonais , Hibridomas , Animais , Anticorpos Monoclonais/imunologia , Especificidade de Anticorpos , Bovinos , Ensaio de Imunoadsorção Enzimática , Hibridomas/imunologia , Imunização , Camundongos Endogâmicos BALB C
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