Your browser doesn't support javascript.
loading
Mostrar: 20 | 50 | 100
Resultados 1 - 20 de 34
Filtrar
Mais filtros










Base de dados
Intervalo de ano de publicação
1.
Life Sci ; 256: 117959, 2020 Sep 01.
Artigo em Inglês | MEDLINE | ID: mdl-32531375

RESUMO

Resveratrol has the ability to promote functional recovery after sciatic nerve crush injury (SNCI), though the mechanism through which this occurs in not fully understood. Resveratrol can promote autophagy, a key process in Wallerian degeneration; thus, we hypothesized that resveratrol could promote recovery from SNCI by promoting Schwann cell autophagy and acceleration of Wallerian degeneration. Motor function recovery was assessed by calculating Sciatic Function Indexes (SFIs) at days 7, 14, 21, 28 post SNCI. Autophagy and myelin clearance were assessed by microtubule-associated protein light chain 3B (LC3B) and myelin protein zero (MPZ) immunofluorescence and Western blot analysis on the fourth day after SNCI. The autophagy of Schwann cells following resveratrol administration was quantified by immunofluorescence in RSC96 cells. Immunofluorescence and Transmission electron microscopy (TEM) were also used in Resveratrol treated sciatic nerve four days post-SNCI to find LC3B positive areas and typical double membrane structures represent for autophagy. The SNCI+resveratrol (crush+Res) groups recovered faster than the SNCI+vehicles (crush+V) group. On day four, almost all of the myelin had regenerated in the crush+Res rats, while the crush+V group's myelin remained intact and the expression levels of LC3-II/I was the highest. On day 28 post-injury, both the control and crush+Res groups' myelin neurofibers reached peak numbers as did the thickness of the myelin sheath. Both in vitro and in vivo immunofluorescence showed that LC3B was colocalized with Schwann cells. This is the first study to observe that resveratrol can promote recovery from SCNI by accelerating the myelin clearance process by promoting autophagy of Schwann cells.


Assuntos
Autofagia/efeitos dos fármacos , Lesões por Esmagamento/fisiopatologia , Compressão Nervosa , Recuperação de Função Fisiológica/efeitos dos fármacos , Resveratrol/farmacologia , Células de Schwann/patologia , Nervo Isquiático/patologia , Nervo Isquiático/fisiopatologia , Animais , Axônios/efeitos dos fármacos , Axônios/patologia , Lesões por Esmagamento/patologia , Masculino , Proteínas Associadas aos Microtúbulos/metabolismo , Atividade Motora/efeitos dos fármacos , Proteína P0 da Mielina/metabolismo , Bainha de Mielina/efeitos dos fármacos , Bainha de Mielina/metabolismo , Fibras Nervosas/efeitos dos fármacos , Fibras Nervosas/patologia , Regeneração Nervosa/efeitos dos fármacos , Ratos Sprague-Dawley , Espécies Reativas de Oxigênio/metabolismo , Células de Schwann/efeitos dos fármacos , Células de Schwann/metabolismo , Nervo Isquiático/efeitos dos fármacos
2.
PLoS One ; 15(4): e0231194, 2020.
Artigo em Inglês | MEDLINE | ID: mdl-32271817

RESUMO

Various injuries to the neural tissues can cause irreversible damage to multiple functions of the nervous system ranging from motor control to cognitive function. The limited treatment options available for patients have led to extensive interest in studying the mechanisms of neuronal regeneration and recovery from injury. Since many neurons are terminally differentiated, by increasing cell survival following injury it may be possible to minimize the impact of these injuries and provide translational potential for treatment of neuronal diseases. While several cell types are known to survive injury through plasma membrane repair mechanisms, there has been little investigation of membrane repair in neurons and even fewer efforts to target membrane repair as a therapy in neurons. Studies from our laboratory group and others demonstrated that mitsugumin 53 (MG53), a muscle-enriched tripartite motif (TRIM) family protein also known as TRIM72, is an essential component of the cell membrane repair machinery in skeletal muscle. Interestingly, recombinant human MG53 (rhMG53) can be applied exogenously to increase membrane repair capacity both in vitro and in vivo. Increasing the membrane repair capacity of neurons could potentially minimize the death of these cells and affect the progression of various neuronal diseases. In this study we assess the therapeutic potential of rhMG53 to increase membrane repair in cultured neurons and in an in vivo mouse model of neurotrauma. We found that a robust repair response exists in various neuronal cells and that rhMG53 can increase neuronal membrane repair both in vitro and in vivo. These findings provide direct evidence of conserved membrane repair responses in neurons and that these repair mechanisms can be targeted as a potential therapeutic approach for neuronal injury.


Assuntos
Regeneração Nervosa , Nervo Isquiático/lesões , Nervo Isquiático/fisiopatologia , Cicatrização , Animais , Linhagem Celular , Membrana Celular/efeitos dos fármacos , Membrana Celular/metabolismo , Lesões por Esmagamento/patologia , Lesões por Esmagamento/fisiopatologia , Modelos Animais de Doenças , Humanos , Proteínas de Membrana/metabolismo , Membranas , Camundongos Endogâmicos C57BL , Regeneração Nervosa/efeitos dos fármacos , Neurônios/efeitos dos fármacos , Neurônios/metabolismo , Neurônios/patologia , Proteínas Recombinantes/farmacologia , Nervo Isquiático/efeitos dos fármacos , Nervo Isquiático/patologia , Proteínas com Motivo Tripartido/farmacologia , Cicatrização/efeitos dos fármacos
3.
PLoS One ; 14(12): e0226626, 2019.
Artigo em Inglês | MEDLINE | ID: mdl-31877172

RESUMO

Ginkgo biloba leaves extract (GBE) was subjected to neuroprotective-guided fractionation to produce eleven fractions with different polarities and constituents. The intermediate polar fraction was shown to be terpene trilactones-enriched fraction (TEGBE). Out of this fraction, pure ginkgolide B (G-B) was further purified and identified based on its spectral data. The effects of GBE and TEGBE were evaluated in comparison to that of G-B in the crush sciatic nerve injury rat model. To evaluate the neuroprotective effects, sixty Wistar male rats were randomly allocated into 6 groups: naive, sham, crush + normal saline, and three treatment groups; crush + GBE, crush + TEGBE, and crush + G-B. Treatments were given one hour following injury, and once daily for 14 days. Neurobehavioral tests, histomorphological examinations, and immunohistochemical analysis of the sciatic nerve and the spinal cord were performed at weeks 3 and 6 post-injury. GBE, TEGBE and G-B were shown to enhance the functional and sensory behavioral parameters and to protect the histological and the ultrastructural elements in the sciatic nerve. Additionally, all treatments prevented spinal cord neurons from further deterioration. It was shown that G-B has the most significant potential effects among all treatments with values that were nearly comparable to those of sham and naive groups.


Assuntos
Lesões por Esmagamento/tratamento farmacológico , Ginkgolídeos/uso terapêutico , Lactonas/uso terapêutico , Fármacos Neuroprotetores/uso terapêutico , Traumatismos dos Nervos Periféricos/tratamento farmacológico , Extratos Vegetais/uso terapêutico , Nervo Isquiático/lesões , Animais , Lesões por Esmagamento/patologia , Masculino , Traumatismos dos Nervos Periféricos/patologia , Ratos Wistar , Nervo Isquiático/efeitos dos fármacos , Nervo Isquiático/patologia
4.
Med Sci Monit ; 25: 10067-10076, 2019 Dec 28.
Artigo em Inglês | MEDLINE | ID: mdl-31882570

RESUMO

BACKGROUND The aim of this study was to explore the effect of metformin by inducing autophagy for enhancing functional recovery of peripheral nerve in rats with sciatic nerve crush injury. MATERIAL AND METHODS Autophagy was determined by electron microscopy, immunofluorescence, and Western blot analysis. Motor function recovery was studied by the footprint intensity method. Axonal growth and regeneration were detected through Western blot while axonal remyelination was analysed through immunocytochemistry. Sensory and functional recovery were assessed by reflexive motor function analysis. RESULTS The present study deciphered the role of autophagy induction by metformin in motor functions and peripheral nerve regeneration following sciatic nerve crush injury in rats. The process was detected by measuring autophagosomes and the expression of microtubule-associated protein 1A/1B-light chain 3 upon metformin treatment of sciatic nerve crush-injured rats. Neurobehavioral recovery by metformin was tested by CatWalk gait analysis, and we quantified expression of myelin basic protein MBP and neurofilament NF200 at the damage sight by immunoblotting. In metformin-treated injured rats, autophagy was upregulated, by which the number of dead cells was decreased. Motor function was also recovered after metformin treatment, which was accompanied by upregulation of MBP and NF200 through autophagy induction. Surprisingly, the motor regenerative capability was reduced by treatment with 3-methyl adenine (an autophagy inhibitor) in nerve-injured rats. CONCLUSIONS Our study revealed that pharmacological induction of autophagy has an important and active role in the regeneration of nerve and motor function regain.


Assuntos
Lesões por Esmagamento/fisiopatologia , Metformina/farmacologia , Compressão Nervosa , Recuperação de Função Fisiológica/efeitos dos fármacos , Nervo Isquiático/lesões , Animais , Autofagia/efeitos dos fármacos , Axônios/metabolismo , Lesões por Esmagamento/patologia , Feminino , Camundongos Endogâmicos C57BL , Atividade Motora/efeitos dos fármacos , Proteína Básica da Mielina/metabolismo , Regeneração Nervosa/efeitos dos fármacos , Condução Nervosa/efeitos dos fármacos , Proteínas de Neurofilamentos/metabolismo , Ratos Sprague-Dawley , Nervo Isquiático/efeitos dos fármacos , Nervo Isquiático/patologia , Nervo Isquiático/ultraestrutura , Regulação para Cima/efeitos dos fármacos
5.
Eur Cytokine Netw ; 30(2): 59-66, 2019 Jun 01.
Artigo em Inglês | MEDLINE | ID: mdl-31486397

RESUMO

Recent studies have demonstrated that nicotine exhibited anti-inflammatory and neuroprotective properties by interacting with the alpha 7 nicotinic acetylcholine receptor (α7nAChR). However, the role of nicotine in regeneration during peripheral nerve injury has not been elucidated. The aim of this study was to investigate whether nicotine down-regulated production of proinflammatory cytokines and promoted peripheral nerve regeneration in rats. Rats challenged with sciatic nerve crush injury were treated with nicotine (1.5 mg/kg), three times per day. The expression of the proinflammatory cytokines tumor necrosis factor alpha (TNF-α) and interleukin (IL-1ß), pinch test results, growth-associated protein 43 (GAP-43) expression, morphometric analyses, and the sciatic functional indexes were determined in sciatic nerves. Treatment with nicotine decreased local levels of TNF-α and IL-1ß, and increased the expression of GAP-43. Nicotine also improved nerve regeneration and functional recovery. The overall protective effects of nicotine were reversed by concomitant treatment with α7nACHR antagonist methyllycaconitine, indicating that nicotine exerted its specific anti-inflammatory and neuroprotective effects through the α7nAChR. These findings show that nicotine administration can provide a potential therapeutic pathway for the treatment of peripheral nerve injury, by a direct protective effect through the α7nAChR-mediated cholinergic anti-inflammatory pathway.


Assuntos
Lesões por Esmagamento/metabolismo , Lesões por Esmagamento/patologia , Citocinas/metabolismo , Mediadores da Inflamação/metabolismo , Fármacos Neuroprotetores/farmacologia , Nicotina/farmacologia , Nervo Isquiático/metabolismo , Nervo Isquiático/patologia , Animais , Modelos Animais de Doenças , Proteína GAP-43/metabolismo , Interleucina-1beta/metabolismo , Masculino , Atividade Motora/efeitos dos fármacos , Regeneração Nervosa/efeitos dos fármacos , Ratos Wistar , Nervo Isquiático/efeitos dos fármacos , Células Receptoras Sensoriais/efeitos dos fármacos , Fator de Necrose Tumoral alfa/metabolismo
6.
Muscle Nerve ; 60(2): 192-201, 2019 08.
Artigo em Inglês | MEDLINE | ID: mdl-31093982

RESUMO

INTRODUCTION: We recently demonstrated the beneficial effects of 4-aminopyridine (4-AP), a potassium channel blocker, in enhancing remyelination and recovery of nerve conduction velocity and motor function after sciatic nerve crush injury in mice. Although muscle atrophy occurs very rapidly after nerve injury, the effect of 4-AP on muscle atrophy and intrinsic muscle contractile function is largely unknown. METHODS: Mice were assigned to sciatic nerve crush injury and no-injury groups and were followed for 3, 7, and 14 days with/without 4-AP or saline treatment. Morphological, functional, and transcriptional properties of skeletal muscle were assessed. RESULTS: In addition to improving in vivo function, 4-AP significantly reduced muscle atrophy with increased muscle fiber diameter and contractile force. Reduced muscle atrophy was associated with attenuated expression of atrophy-related genes and increased expression of proliferating stem cells. DISCUSSION: These findings provide new insights into the potential therapeutic benefits of 4-AP against nerve injury-induced muscle atrophy and dysfunction. Muscle Nerve 60: 192-201, 2019.


Assuntos
4-Aminopiridina/farmacologia , Lesões por Esmagamento/fisiopatologia , Músculo Esquelético/efeitos dos fármacos , Atrofia Muscular/patologia , Traumatismos dos Nervos Periféricos/fisiopatologia , Bloqueadores dos Canais de Potássio/farmacologia , Remielinização/efeitos dos fármacos , Nervo Isquiático/efeitos dos fármacos , Animais , Lesões por Esmagamento/metabolismo , Lesões por Esmagamento/patologia , Proteína Forkhead Box O1/efeitos dos fármacos , Proteína Forkhead Box O1/genética , Proteína Forkhead Box O3/efeitos dos fármacos , Proteína Forkhead Box O3/genética , Camundongos , Proteínas Musculares/efeitos dos fármacos , Proteínas Musculares/genética , Músculo Esquelético/inervação , Músculo Esquelético/patologia , Músculo Esquelético/fisiopatologia , Atrofia Muscular/genética , Traumatismos dos Nervos Periféricos/genética , Traumatismos dos Nervos Periféricos/patologia , Regeneração/efeitos dos fármacos , Nervo Isquiático/lesões , Nervo Isquiático/patologia , Nervo Isquiático/fisiopatologia , Proteínas com Motivo Tripartido/efeitos dos fármacos , Proteínas com Motivo Tripartido/genética , Ubiquitina-Proteína Ligases/efeitos dos fármacos , Ubiquitina-Proteína Ligases/genética
7.
Histochem Cell Biol ; 152(2): 89-107, 2019 Aug.
Artigo em Inglês | MEDLINE | ID: mdl-31093775

RESUMO

Recently, we evaluated capillary indices without discrimination by fiber type in rat extensor digitorum longus muscle (EDL) 4 weeks after nerve cut (NC), after double nerve crush (double NCR) and in two controls, from the start (CON-1) and the end (CON-2) of the experiment. In the present study, we determined the capillary indices related to specific myosin heavy chain (MyHC) fiber types. Fiber-type composition and local capillarity were assessed from a single, composite, multicolor image, where different MyHC-fiber types and capillaries were shown simultaneously. Applying local capillary indices [the number of capillaries around fiber (CAF) and the CAF scaled to fiber perimeter (CAF/FP)], to specific MyHC-fiber types, we found changes relevant to neuro-muscular studies. In the NC group, only type-2x fibers had a significantly lower CAF, and in the double NCR group, only type-2a fibers had a higher CAF in comparison with both controls. Both types of nerve injury elicited two responses: a coupled regulation of fiber size and capillarity in the oxidative, type 2a fibers and a capillarity independent regulation of fiber size in the glycolytic type-2b fibers. All subtypes of type-2 fibers had a better capillary supply (higher CAF/FP) in the NC and double NCR than in CON-2. The highest improvement was observed in type-2b fibers; this change was mirrored in an oxidative shift only in the double NCR group. Adopting fiber-type-specific capillary indices improves data analysis of rat EDL muscle samples.


Assuntos
Lesões por Esmagamento/metabolismo , Fibras Musculares Esqueléticas/metabolismo , Cadeias Pesadas de Miosina/metabolismo , Animais , Ação Capilar , Lesões por Esmagamento/patologia , Lesões por Esmagamento/cirurgia , Masculino , Fibras Musculares Esqueléticas/química , Cadeias Pesadas de Miosina/análise , Procedimentos Neurocirúrgicos , Ratos , Ratos Wistar
8.
Adv Skin Wound Care ; 32(3): 131-138, 2019 Mar.
Artigo em Inglês | MEDLINE | ID: mdl-30801351

RESUMO

Pressure injuries/ulcers are a global health issue, and there is a need for clinicians from many countries and continents to express their opinions on the terminology change (pressure ulcer to injury) and revised staging definitions. A convenience, opinion survey sample of clinicians from the Western Asia Gulf Region enrolled in a yearlong wound care course participated by expressing their opinion about these changes. Results reveal support for the pressure injury terminology and the revised staging definitions.


Assuntos
Lesão por Pressão/classificação , Lesão por Pressão/patologia , Terminologia como Assunto , Comitês Consultivos , Lesões por Esmagamento/classificação , Lesões por Esmagamento/patologia , Humanos , Lesão por Pressão/terapia , Índice de Gravidade de Doença , Higiene da Pele/enfermagem , Cicatrização
9.
Acta Biomater ; 86: 185-193, 2019 03 01.
Artigo em Inglês | MEDLINE | ID: mdl-30660008

RESUMO

Promoting axon growth after peripheral nerve injury may support recovery. Soluble laminin polymers formed at pH 4 (aLam) accelerate axon growth from adult dorsal root ganglion neurons in vitro. We used an adult rat model of a peripheral (peroneal) nerve crush to investigate whether an injection of aLam enhances axon growth and functional recovery in vivo. Rats that received an injection of aLam into the crush at 2 days post-injury show significant improvements in hind limb motor function at 2 and 5 weeks after injury compared with control rats that received phosphate-buffered saline. Functional improvement was not associated with changes in sensitivity to thermal or mechanical stimuli. Treatment with aLam decreased the occurrence of autophagia and abolished non-compliance with treadmill walking. Rats treated with aLam showed increased axon presence in the crush site at 2 weeks post-injury and larger axon diameter at 10 weeks post-injury compared with controls. Treatment with aLam did not affect Schwann cell presence or axon myelination. Our results demonstrated that aLam accelerates axon growth and maturity in a crushed peroneal nerve associated with expedited hind limb motor function recovery. Our data support the therapeutic potential of injectable aLam polymers for treatment of peripheral nerve crush injuries. STATEMENT OF SIGNIFICANCE: Incidence of peripheral nerve injury has been estimated to be as high as 5% of all cases entering a Level 1 trauma center and the majority of cases are young males. Peripheral nerves have some endogenous repair capabilities, but overall recovery of function remains limited, which typically has devastating effects on the individual, family, and society, as wages are lost and rehabilitation is extended until the nerves can repair. We report here that laminin polymers injected into a crush accelerated repair and recovery, had no adverse effects on sensory function, obliterated non-compliance for walking tests, and decreased the occurrence of autophagia. These data support the use of laminin polymers for safe and effective recovery after peripheral nerve injury.


Assuntos
Lesões por Esmagamento/fisiopatologia , Laminina/farmacologia , Compressão Nervosa , Regeneração Nervosa/efeitos dos fármacos , Traumatismos dos Nervos Periféricos/fisiopatologia , Polímeros/farmacologia , Animais , Axônios/efeitos dos fármacos , Axônios/patologia , Lesões por Esmagamento/patologia , Feminino , Concentração de Íons de Hidrogênio , Atividade Motora/efeitos dos fármacos , Bainha de Mielina/metabolismo , Traumatismos dos Nervos Periféricos/patologia , Nervo Fibular/efeitos dos fármacos , Nervo Fibular/patologia , Nervo Fibular/fisiopatologia , Condicionamento Físico Animal , Ratos Sprague-Dawley , Células de Schwann/efeitos dos fármacos , Células de Schwann/metabolismo
10.
Forensic Sci Med Pathol ; 15(2): 319-323, 2019 Jun.
Artigo em Inglês | MEDLINE | ID: mdl-30535907

RESUMO

An adult male skeleton was submitted to the Department of Anatomy at the University of Belgrade for evaluation. It was believed to represent the remains of a second to third century Christian saint from the Lesje Monastery in central Serbia. Examination of the remains revealed an old crush fracture of a thoracic vertebra and an unusual, probably congenital, malformation of the atlanto-occipital joint with deformation of the left occipital condyle and resultant narrowing of the foramen magnum. Although the occipital malformations were most likely congenital, they may still have caused, or contributed to, death by compression of the underlying upper cervical spinal cord.


Assuntos
Articulação Atlantoccipital/anormalidades , Lesões por Esmagamento/patologia , Santos/história , Vértebras Torácicas/lesões , Adulto , Forame Magno/anormalidades , Forame Magno/diagnóstico por imagem , Antropologia Forense , História Antiga , Humanos , Masculino , Osso Occipital/anormalidades , Osso Occipital/diagnóstico por imagem , Religião e Medicina , Sérvia , Crânio/anatomia & histologia , Vértebras Torácicas/patologia , Tomografia Computadorizada por Raios X
11.
Life Sci ; 215: 22-30, 2018 Dec 15.
Artigo em Inglês | MEDLINE | ID: mdl-30391465

RESUMO

AIMS: Peripheral nerve injury represents a substantial clinical problem with insufficient or unsatisfactory treatment options. Current researches have extensively focused on the new approaches for the treatment of peripheral nerve injuries. Carnosine is a naturally occurring pleotropic dipeptide and has many biological functions such as antioxidant property. In the present study, we examined the regenerative ability of carnosine after sciatic nerve crush injury using behavioral, biochemical, histological and ultrastructural evaluations. MATERIALS AND METHODS: Seventy-two rats were divided into six groups including control, sham, crush and carnosine (10, 20 and 40 mg/kg) groups. Crush injury in left sciatic nerve was induced by a small haemostatic forceps. Carnosine was administered for 15 consecutive days after induction of crush injury. Sciatic functional index (SFI) was recorded weekly. Histopathological and ultrastructural evaluations were made using light and electron microscopes, respectively. Sciatic nerve tissue malondialdehyde (MDA), superoxide dismutase (SOD) and tumor necrosis factor-alpha (TNF-α) levels were measured. Gastrocnemius muscle weight was determined. KEY FINDINGS: Carnosine at the doses of 20 and 40 mg/kg accelerated SFI recovery. Wallerian degeneration severity and myelinated fibers density, myelin sheath thickness and diameter as well as ultrastructural changes of myelinated axons were improved. It also recovered nerve tissue biochemical (MDA, SOD and TNF-α) changes induced by crush injury. Muscle weight ratio was reached to near normal values. Our results suggest a regenerative effect of carnosine. Inhibition of oxidative stress and inflammatory pathways, along with provocation of myelination and prevention of muscular atrophy might be involved in this effect of carnosine. SIGNIFICANCE: Carnosine treatment might be considered as a therapeutic agent for peripheral nerve regeneration and its functional recovery.


Assuntos
Carnosina/farmacologia , Lesões por Esmagamento/tratamento farmacológico , Regeneração Nervosa/efeitos dos fármacos , Traumatismos dos Nervos Periféricos/tratamento farmacológico , Nervo Isquiático/efeitos dos fármacos , Animais , Antioxidantes/administração & dosagem , Antioxidantes/farmacologia , Axônios/efeitos dos fármacos , Axônios/patologia , Carnosina/administração & dosagem , Lesões por Esmagamento/patologia , Relação Dose-Resposta a Droga , Masculino , Bainha de Mielina/efeitos dos fármacos , Bainha de Mielina/patologia , Estresse Oxidativo/efeitos dos fármacos , Traumatismos dos Nervos Periféricos/patologia , Ratos , Ratos Wistar , Recuperação de Função Fisiológica/efeitos dos fármacos , Nervo Isquiático/lesões , Degeneração Walleriana/tratamento farmacológico , Degeneração Walleriana/patologia
12.
Neuropharmacology ; 139: 98-116, 2018 09 01.
Artigo em Inglês | MEDLINE | ID: mdl-30018000

RESUMO

Traumatic injuries to peripheral nerves are frequent, however, specific pharmacological treatments are currently lacking. Curcumin has antioxidant, anti-inflammatory and neuroprotective properties but high oral doses are required for therapeutic use, particularly due to its low bioavailability. The aim of the present study was to investigate the effects of local and continuous treatment using low curcumin doses on functional recovery and nerve regeneration after rat sciatic nerve crush (SNC). Curcumin was administered by osmotic pumps with a catheter delivering the drug at the injury site (0.2 mg/day for 4 weeks). Functionally, early improvements in mechanical sensitivity, finger spacing of the injured paw, skilful walking and grip strength were observed in curcumin-treated animals. The curcumin treatment increased expression of compact myelin proteins (MPZ and PMP22), myelin sheath thickness and, correspondingly, increased motor and sensitive nerve conduction velocity. Microscopic analysis of gastrocnemius muscle indicated a curcumin-induced decrease in neurogenic lesions. Curcumin treatment reduced the production of reactive oxygen species (ROS) (which were notably produced by macrophages), lipid peroxidation and increased expression of transcription factor Nrf2. In silico analyses indicated that curcumin combines all the characteristics required to be an efficient lipid peroxidation inhibitor at the heart of biological membranes, hence protecting their degradation due to ROS. This antioxidant capacity is likely to contribute to the beneficial effects of curcumin after SNC injury. These results demonstrate that, when administrated locally, low doses of curcumin represent a promising therapy for peripheral nerve regeneration.


Assuntos
Antioxidantes/farmacologia , Lesões por Esmagamento/tratamento farmacológico , Curcumina/farmacologia , Recuperação de Função Fisiológica/efeitos dos fármacos , Remielinização/efeitos dos fármacos , Nervo Isquiático/lesões , Animais , Células Cultivadas , Lesões por Esmagamento/patologia , Lesões por Esmagamento/fisiopatologia , Peroxidação de Lipídeos/efeitos dos fármacos , Masculino , Simulação de Dinâmica Molecular , Músculo Esquelético/efeitos dos fármacos , Músculo Esquelético/patologia , Músculo Esquelético/fisiopatologia , Fator 2 Relacionado a NF-E2/metabolismo , Condução Nervosa/efeitos dos fármacos , Fármacos Neuroprotetores/farmacologia , Estresse Oxidativo/efeitos dos fármacos , Distribuição Aleatória , Ratos Sprague-Dawley , Recuperação de Função Fisiológica/fisiologia , Remielinização/fisiologia , Nervo Isquiático/efeitos dos fármacos , Nervo Isquiático/patologia , Nervo Isquiático/fisiopatologia
13.
Muscle Nerve ; 58(4): 566-572, 2018 10.
Artigo em Inglês | MEDLINE | ID: mdl-30028517

RESUMO

INTRODUCTION: To restore full function following nerve crush injuries is critical but challenging. In an attempt to develop a viable therapy, we evaluated the effect of rat adipose-derived stem cells (rASC) in 2 different settings of a sciatic crush injury model. METHODS: In the first group, after 14 days of nerve crush injury, rASCs were injected distal to the lesion under ultrasound guidance. In the other group, alleviation of compression through clip removal (CR) was combined with epineural injection of rASCs. Gait analyses, MRI, gastrocnemius muscle weight ratio (MWR), and histomorphometry were performed for outcome analysis. RESULTS: CR combined with rASC injection resulted in less muscle atrophy, as evidenced by MWR. These findings are further supported by better functional and anatomical outcomes. DISCUSSION: Animals treated with CR and epineural stem cell injection showed enhanced anatomical and functional recovery. Muscle Nerve 58: 566-572, 2018.


Assuntos
Tecido Adiposo/citologia , Lesões por Esmagamento/patologia , Transplante de Células-Tronco Mesenquimais , Regeneração Nervosa , Traumatismos dos Nervos Periféricos/patologia , Nervo Isquiático/lesões , Animais , Imagem de Tensor de Difusão , Feminino , Análise da Marcha , Imagem por Ressonância Magnética , Músculo Esquelético/patologia , Tamanho do Órgão , Ratos , Ratos Sprague-Dawley , Nervo Isquiático/patologia , Nervo Isquiático/fisiologia
14.
Exp Eye Res ; 174: 93-97, 2018 09.
Artigo em Inglês | MEDLINE | ID: mdl-29856984

RESUMO

In this study we have compared the response to optic nerve crush (ONC) and to optic nerve transection (ONT) of the general population of retinal ganglion cells in charge of the image-forming visual functions that express Brn3a (Brn3a+RGCs) with that of the sub-population of non-image forming RGCs that express melanopsin (m+RGCs). Intact animals were used as control. ONT and ONC were performed at 0.5 mm from the optic disk, and retinas dissected 3, 5, 7, 14, 30, 45 or 90 days later (n = 5/injury/time point). In all the retinas, Brn3a+RGCs and m+RGCs were identified and their survival analyzed quantitatively and topographically. There were no differences in the course of RGC loss between lesions. The decrease of RGCs was significant at short time points (3 or 5 days for Brn3a+ or m+ RGCs, respectively) and, up to 14 days, the course of loss of both RGC populations was similar, surviving at this time point between 20 and 22% of their original population. However, while the loss of Brn3a+RGCs continues steadily up to 90 days when only 5-6% of them still remain, the loss of m+RGCs stops at 14 days, and the proportion of surviving m+RGCs remains constant up to 90 days (26-30%). In conclusion, m+RGC do not respond to axotomy in the same way than the rest of RGCs, and so whilst image-forming RGCs die in two exponential phases a quick one and a slow protracted one, non-image forming RGCs die only during the first quick phase.


Assuntos
Traumatismos do Nervo Óptico/patologia , Células Ganglionares da Retina/patologia , Opsinas de Bastonetes/metabolismo , Animais , Sobrevivência Celular , Lesões por Esmagamento/patologia , Modelos Animais de Doenças , Camundongos
15.
Biomater Sci ; 6(8): 2059-2072, 2018 Jul 24.
Artigo em Inglês | MEDLINE | ID: mdl-29932177

RESUMO

Non-viral vector gene delivery is generally limited by its potential toxicity problems, poor transfection abilities, serum stability, or relatively complex construction processes of modified polyplexes. Thus, we develop an efficient and stable polyplex system through convenient construction methods. Here, polyethyleneimine (PEI) 1.8 kDa and glutaraldehyde (GA) are used to construct a novel twice-condensed pDNA polyplex system using a one-pot construction method, including pH-responsive C[double bond, length as m-dash]N linkages by which different PEI molecules on one single polyplex can link with each other. In this system, smaller particle sizes, higher zeta potentials and better serum stabilities are achieved without PEGylation or other chemical modifications using lyophobic segments, but via pH-responsive linkages that ensure the escape of nucleic acids. This polyplex system is used to deliver the pDNA of vascular endothelial growth factor (VEGF) whose half-life period in vivo is only around 30 minutes. Compared with polyplexes prepared using PEI 25 kDa, cells and rats treated with twice-condensed VEGF pDNA polyplexes express significantly more VEGF or myelin basic protein (MBP), and this new polyplex system showed fewer adverse effects in vitro and in vivo. In addition, revascularization and neurogenesis are also discovered in the rat sciatic nerve crush injury model.


Assuntos
Lesões por Esmagamento/tratamento farmacológico , DNA/química , Glutaral/farmacologia , Polietilenoimina/farmacologia , Nervo Isquiático/efeitos dos fármacos , Animais , Apoptose/efeitos dos fármacos , Sobrevivência Celular/efeitos dos fármacos , Lesões por Esmagamento/metabolismo , Lesões por Esmagamento/patologia , DNA/genética , Modelos Animais de Doenças , Relação Dose-Resposta a Droga , Técnicas de Transferência de Genes , Glutaral/química , Células Endoteliais da Veia Umbilical Humana/efeitos dos fármacos , Células Endoteliais da Veia Umbilical Humana/metabolismo , Humanos , Concentração de Íons de Hidrogênio , Bloqueio Nervoso , Tamanho da Partícula , Plasmídeos/química , Plasmídeos/genética , Polietilenoimina/química , Ratos , Células de Schwann/efeitos dos fármacos , Células de Schwann/metabolismo , Nervo Isquiático/metabolismo , Nervo Isquiático/patologia , Relação Estrutura-Atividade , Fatores de Crescimento do Endotélio Vascular/química , Fatores de Crescimento do Endotélio Vascular/metabolismo
16.
J Hand Surg Asian Pac Vol ; 23(2): 232-237, 2018 Jun.
Artigo em Inglês | MEDLINE | ID: mdl-29734902

RESUMO

BACKGROUND: The success of replantation following traumatic amputation is determined by the quality of the vascular anastomoses. The purpose of this study was to assess the vascularity of injured arteries from traumatically amputated digits using arteriographic and histopathological analysis. METHODS: 25 amputated digits were included in the study. Crush and avulsion injuries were evaluated according to the Venkatramani classification. The amputated arteries were dissected under a microscope, and the arterial route determined with a transducer. Arteriography using fluoroscopy was evaluated by a radiologist. The area thought to be damaged was dissected and 2-mm slices taken for histopathological examination, and scored using the parameters of fibrin accumulation, oedema, separation, and bleeding. RESULTS: Arterial flow was observed in 6 of 7 in the avulsion group. In the crush group, arterial flow was observed in 11 of 16 cases. On histopathological examination in all cases there were 2 or more findings of either oedema, fibrin formation, bleeding or hernia. These findings were more common in the crush group then the avulsion group. CONCLUSIONS: The intravascular introduction of radio contrast agents to amputated digit prior to replantation may give further information particularly in avulsion amputations.


Assuntos
Amputação Traumática/diagnóstico por imagem , Amputação Traumática/patologia , Traumatismos dos Dedos/diagnóstico por imagem , Traumatismos dos Dedos/patologia , Dedos/irrigação sanguínea , Adulto , Angiografia , Meios de Contraste , Lesões por Esmagamento/diagnóstico por imagem , Lesões por Esmagamento/patologia , Desenluvamentos Cutâneos/diagnóstico por imagem , Desenluvamentos Cutâneos/patologia , Edema/patologia , Feminino , Fibrina/metabolismo , Dedos/diagnóstico por imagem , Fluoroscopia , Hemorragia/patologia , Hérnia/patologia , Humanos , Masculino , Microscopia , Pessoa de Meia-Idade , Estudos Prospectivos , Fluxo Sanguíneo Regional , Ácidos Tri-Iodobenzoicos
17.
Mol Med Rep ; 17(3): 4360-4368, 2018 Mar.
Artigo em Inglês | MEDLINE | ID: mdl-29328458

RESUMO

In the present study, the effects of hyaluronic acid (HA) combined with chitosan conduit on peripheral nerve scarring and regeneration were investigated in a rat model of peripheral nerve crush injury. A total of 60 Sprague-Dawley rats were randomly distributed into four groups (15 rats in each group), in which the nerve was either not treated (control group) or treated with chitosan conduit, hyaluronic acid, or chitosan conduit coupled with hyaluronic acid following clamp injury to the sciatic nerve. The surgical sites were evaluated by assessing the sciatic functional index, the degree of scar adhesions, the numbers of myelinated nerve fibers, the average diameter of myelinated nerve fibers and the myelin sheath thickness. Larger epineurial scar thickness was observed in the control groups compared with the treatment groups at 4, 8 and 12 weeks following surgery. There was no significant difference in scar adhesion among the four groups at 4 weeks following surgery. However, animals receiving chitosan coupled with HA demonstrated better neural recovery, as measured by reduced nerve adherence to surrounding tissues, less scar adhesion, increased number of axons, nerve fiber diameter and myelin thickness. In conclusion, the application of chitosan conduit combined with HA, to a certain extent, inhibited sciatic nerve extraneural scaring and adhesion, and promoted neural regeneration and recovery.


Assuntos
Quitosana/farmacologia , Cicatriz/prevenção & controle , Ácido Hialurônico/farmacologia , Regeneração Nervosa/efeitos dos fármacos , Nervo Isquiático/efeitos dos fármacos , Aderências Teciduais/prevenção & controle , Animais , Cicatriz/patologia , Lesões por Esmagamento/tratamento farmacológico , Lesões por Esmagamento/patologia , Lesões por Esmagamento/cirurgia , Feminino , Masculino , Bainha de Mielina/efeitos dos fármacos , Bainha de Mielina/fisiologia , Bainha de Mielina/ultraestrutura , Regeneração Nervosa/fisiologia , Ratos , Ratos Sprague-Dawley , Nervo Isquiático/lesões , Nervo Isquiático/fisiologia , Nervo Isquiático/ultraestrutura , Neuropatia Ciática/tratamento farmacológico , Neuropatia Ciática/patologia , Neuropatia Ciática/cirurgia , Aderências Teciduais/patologia , Engenharia Tecidual , Tecidos Suporte
18.
J Forensic Leg Med ; 52: 110-115, 2017 Nov.
Artigo em Inglês | MEDLINE | ID: mdl-28892750

RESUMO

Traumatic (crush) asphyxia is a rare condition caused by severe compression of the chest and trunk leading to often extreme so-called asphyxial signs, including cyanosis in head and neck regions, multiple petechiae, and subconjunctival haemorrhage as well as neurological manifestations. AIMS: To investigate the neuropathology and brain weight in traumatic asphyxia caused by different accidents such as industrial accidents and road traffic collision. MATERIAL AND METHODS: Post mortem records of 20 cases of traumatic asphyxia (TA) resulting from different causes of which four brains are available for comprehensive neuropathological examination. The expected brain weights for given body height and associated 95% confidence range were calculated according to the following formula: baseline brain weight (BBW) + body height x rate (g/cm). The 95% confidence range was calculated by adding and subtracting the standard error (SE) x 1.96 (7-8). RESULTS: There was a trend for higher brain weight in the TA cohort but it was not significant (1494 g vs 1404 g, p = 0.1). The upper limits of the brain weight of 95% confidence was 1680 g vs 1660 g, p = 0.9. The neuropathological examination of four available brains from the TA cohort showed severe congestion of blood vessels, perivascular haemorrhages and occasional ßAPP deposits consistent with early axonal disruption. CONCLUSION: Brain examination is informative as part of investigation of TA. Developing ischaemic changes and an increase in brain weight are the most likely indicators of a prolonged period of patient's survival.


Assuntos
Asfixia/patologia , Encéfalo/patologia , Lesões por Esmagamento/patologia , Traumatismos Torácicos/patologia , Adulto , Idoso , Idoso de 80 Anos ou mais , Precursor de Proteína beta-Amiloide/metabolismo , Biomarcadores/metabolismo , Encéfalo/metabolismo , Isquemia Encefálica/patologia , Feminino , Patologia Legal , Humanos , Hemorragias Intracranianas/patologia , Masculino , Pessoa de Meia-Idade , Tamanho do Órgão , Adulto Jovem
19.
J Cell Biol ; 216(11): 3655-3675, 2017 11 06.
Artigo em Inglês | MEDLINE | ID: mdl-28877995

RESUMO

Axon degeneration is an early event and pathological in neurodegenerative conditions and nerve injuries. To discover agents that suppress neuronal death and axonal degeneration, we performed drug screens on primary rodent neurons and identified the pan-kinase inhibitor foretinib, which potently rescued sympathetic, sensory, and motor wt and SOD1 mutant neurons from trophic factor withdrawal-induced degeneration. By using primary sympathetic neurons grown in mass cultures and Campenot chambers, we show that foretinib protected neurons by suppressing both known degenerative pathways and a new pathway involving unliganded TrkA and transcriptional regulation of the proapoptotic BH3 family members BimEL, Harakiri,and Puma, culminating in preservation of mitochondria in the degenerative setting. Foretinib delayed chemotherapy-induced and Wallerian axonal degeneration in culture by preventing axotomy-induced local energy deficit and preserving mitochondria, and peripheral Wallerian degeneration in vivo. These findings identify a new axon degeneration pathway and a potentially clinically useful therapeutic drug.


Assuntos
Anilidas/farmacologia , Lesões por Esmagamento/tratamento farmacológico , Mitocôndrias/efeitos dos fármacos , Neurônios/efeitos dos fármacos , Fármacos Neuroprotetores/farmacologia , Inibidores de Proteínas Quinases/farmacologia , Quinolinas/farmacologia , Receptor trkA/antagonistas & inibidores , Nervo Isquiático/efeitos dos fármacos , Neuropatia Ciática/tratamento farmacológico , Degeneração Walleriana , Fibras Adrenérgicas/efeitos dos fármacos , Fibras Adrenérgicas/enzimologia , Fibras Adrenérgicas/patologia , Animais , Apoptose/efeitos dos fármacos , Proteínas Reguladoras de Apoptose/genética , Proteínas Reguladoras de Apoptose/metabolismo , Axônios/efeitos dos fármacos , Axônios/enzimologia , Axônios/patologia , Células Cultivadas , Lesões por Esmagamento/enzimologia , Lesões por Esmagamento/genética , Lesões por Esmagamento/patologia , Citoproteção , Modelos Animais de Doenças , Relação Dose-Resposta a Droga , Genótipo , Camundongos Endogâmicos C57BL , Camundongos Transgênicos , Mitocôndrias/enzimologia , Mitocôndrias/patologia , Neurônios Motores/efeitos dos fármacos , Neurônios Motores/enzimologia , Neurônios Motores/patologia , Mutação , Neurônios/enzimologia , Neurônios/patologia , Fenótipo , Fosforilação , Ratos Sprague-Dawley , Receptor trkA/genética , Receptor trkA/metabolismo , Nervo Isquiático/enzimologia , Nervo Isquiático/lesões , Nervo Isquiático/patologia , Neuropatia Ciática/enzimologia , Neuropatia Ciática/genética , Neuropatia Ciática/patologia , Células Receptoras Sensoriais/efeitos dos fármacos , Células Receptoras Sensoriais/enzimologia , Células Receptoras Sensoriais/patologia , Transdução de Sinais , Superóxido Dismutase-1/genética , Superóxido Dismutase-1/metabolismo , Fatores de Tempo , Transcrição Genética
20.
J Neurosurg Spine ; 27(5): 593-613, 2017 Nov.
Artigo em Inglês | MEDLINE | ID: mdl-28777065

RESUMO

OBJECTIVE This study examined the capacity of the major polyphenolic green tea extract (-)-epigallocatechin-3-gallate (EGCG) to suppress oxidative stress and stimulate the recovery and prompt the regeneration of sciatic nerve after crush injury. METHODS Adult male Wistar rats were randomly assigned to one of 4 groups: 1) Naïve, 2) Sham (sham injury, surgical control group), 3) Crush (sciatic nerve crush injury treated with saline), and 4) Crush+EGCG (sciatic nerve crush injury treated with intraperitoneally administered EGCG, 50 mg/kg). All animals were tested for motor and sensory neurobehavioral parameters throughout the study. Sciatic nerve and spinal cord tissues were harvested and processed for morphometric and stereological analysis. For the biochemical assays, the time points were Day 1, Day 7, Day 14, and Day 28 after nerve injury. RESULTS After sciatic nerve crush injury, the EGCG-treated animals (Crush+EGCG group) showed significantly better recovery of foot position and toe spread and 50% greater improvement in motor recovery than the saline-treated animals (Crush group). The Crush+EGCG group displayed an early hopping response at the beginning of the 3rd week postinjury. Animals in the Crush+EGCG group also showed a significant reduction in mechanical allodynia and hyperalgesia latencies and significant improvement in recovery from nociception deficits in both heat withdrawal and tail flick withdrawal latencies compared with the Crush group. In both the Crush+EGCG and Crush groups, quantitative evaluation revealed significant morphological evidence of neuroregeneration according to the following parameters: mean cross-sectional area of axons, myelin thickness in the sciatic nerve (from Week 4 to Week 8), increase of myelin basic protein concentration and gene expression in both the injured sciatic nerve and spinal cord, and fiber diameter to axon diameter ratio and myelin thickness to axon diameter ratio at Week 2 after sciatic nerve injury. However, the axon area remained much smaller in both the Crush+EGCG and Crush groups compared with the Sham and Naïve groups. The number of axons per unit area was significantly decreased in the Crush+EGCG and Crush groups compared with controls. Sciatic nerve injury produced generalized oxidative stress manifested as a significant increase of isoprostanes in the urine and decrease of the total antioxidant capacity (TAC) of the blood from Day 7 until Day 14. EGCG-treated rats showed significantly less increase of isoprostanes than saline-treated animals and also showed full recovery of TAC levels by Day 14 after nerve injury. In spinal cord tissue analysis, EGCG-treated animals showed induced glutathione reductase and suppressed induction of heme oxygenase 1 gene expression compared with nontreated animals. CONCLUSIONS EGCG treatment suppressed the crush-induced production of isoprostanes and stimulated the recovery of the TAC and was associated with remarkable alleviation of motor and sensory impairment and significant histomorphological evidence of neuronal regeneration following sciatic nerve crush injury in rats. The findings of this study suggest that EGCG can be used as an adjunctive therapeutic remedy for nerve injury. However, further investigations are needed to establish the antioxidative mechanism involved in the regenerative process after nerve injury. Only upregulation of glutathione reductase supports the idea that EGCG is acting indirectly via induction of enzymes or transcription factors.


Assuntos
Antioxidantes/farmacologia , Catequina/análogos & derivados , Lesões por Esmagamento/tratamento farmacológico , Traumatismos dos Nervos Periféricos/tratamento farmacológico , Nervo Isquiático/efeitos dos fármacos , Nervo Isquiático/lesões , Animais , Axônios/efeitos dos fármacos , Axônios/patologia , Catequina/farmacologia , Lesões por Esmagamento/patologia , Lesões por Esmagamento/fisiopatologia , Modelos Animais de Doenças , Hiperalgesia/tratamento farmacológico , Hiperalgesia/patologia , Hiperalgesia/fisiopatologia , Masculino , Atividade Motora/efeitos dos fármacos , Atividade Motora/fisiologia , Regeneração Nervosa/efeitos dos fármacos , Regeneração Nervosa/fisiologia , Fármacos Neuroprotetores/farmacologia , Estresse Oxidativo/efeitos dos fármacos , Estresse Oxidativo/fisiologia , Traumatismos dos Nervos Periféricos/patologia , Traumatismos dos Nervos Periféricos/fisiopatologia , RNA Mensageiro/metabolismo , Distribuição Aleatória , Ratos Wistar , Recuperação de Função Fisiológica/efeitos dos fármacos , Nervo Isquiático/patologia , Nervo Isquiático/fisiopatologia , Neuropatia Ciática/tratamento farmacológico , Neuropatia Ciática/patologia , Neuropatia Ciática/fisiopatologia , Medula Espinal/efeitos dos fármacos , Medula Espinal/patologia , Medula Espinal/fisiopatologia
SELEÇÃO DE REFERÊNCIAS
DETALHE DA PESQUISA
...