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Article in Chinese | WPRIM | ID: wpr-921772


When ischemia or hemorrhagic stroke occurs, astrocytes are activated by a variety of endogenous regulatory factors to become reactive astrocytes. Subsequently, reactive astrocytes proliferate, differentiate, and migrate around the lesion to form glial scar with the participation of microglia, neuron-glial antigen 2(NG2) glial cells, and extracellular matrix. The role of glial scars at different stages of stroke injury is different. At the middle and late stages of the injury, the secreted chondroitin sulfate proteoglycan and chondroitin sulfate are the main blockers of axon regeneration and nerve function recovery. Targeted regulation of glial scars is an important pathway for neurological rehabilitation after stroke. Chinese medicine has been verified to be effective in stroke rehabilitation in clinical practice, possibly because it has the functions of promoting blood resupply, anti-inflammation, anti-oxidative stress, inhibiting cell proliferation and differentiation, and benign intervention in glial scars. This study reviewed the pathological process and signaling mechanisms of glial scarring after stroke, as well as the intervention of traditional Chinese medicine upon glial scar, aiming to provide theoretical reference and research evidence for developing Chinese medicine against stroke in view of targeting glial scarring.

Astrocytes , Axons/pathology , Cicatrix/pathology , Gliosis/pathology , Humans , Medicine, Chinese Traditional , Nerve Regeneration , Stroke/drug therapy
Braz. j. med. biol. res ; 49(4): e5106, 2016. graf
Article in English | LILACS | ID: biblio-951668


After a traumatic injury to the central nervous system, the distal stumps of axons undergo Wallerian degeneration (WD), an event that comprises cytoskeleton and myelin breakdown, astrocytic gliosis, and overexpression of proteins that inhibit axonal regrowth. By contrast, injured neuronal cell bodies show features characteristic of attempts to initiate the regenerative process of elongating their axons. The main molecular event that leads to WD is an increase in the intracellular calcium concentration, which activates calpains, calcium-dependent proteases that degrade cytoskeleton proteins. The aim of our study was to investigate whether preventing axonal degeneration would impact the survival of retinal ganglion cells (RGCs) after crushing the optic nerve. We observed that male Wistar rats (weighing 200-400 g; n=18) treated with an exogenous calpain inhibitor (20 mM) administered via direct application of the inhibitor embedded within the copolymer resin Evlax immediately following optic nerve crush showed a delay in the onset of WD. This delayed onset was characterized by a decrease in the number of degenerated fibers (P<0.05) and an increase in the number of preserved fibers (P<0.05) 4 days after injury. Additionally, most preserved fibers showed a normal G-ratio. These results indicated that calpain inhibition prevented the degeneration of optic nerve fibers, rescuing axons from the process of axonal degeneration. However, analysis of retinal ganglion cell survival demonstrated no difference between the calpain inhibitor- and vehicle-treated groups, suggesting that although the calpain inhibitor prevented axonal degeneration, it had no effect on RGC survival after optic nerve damage.

Animals , Male , Polyvinyls/pharmacology , Retinal Ganglion Cells/drug effects , Axons/drug effects , Wallerian Degeneration/drug therapy , Glycoproteins/pharmacology , Optic Nerve Injuries/drug therapy , Axons/pathology , Immunohistochemistry , Cell Survival/drug effects , Treatment Outcome , Cell Death/drug effects , Cell Death/physiology , Rats, Wistar , Optic Nerve Injuries/pathology , Microscopy, Electron, Transmission , Nerve Crush
Int. j. morphol ; 33(3): 1002-1008, Sept. 2015. ilus
Article in English | LILACS | ID: lil-762577


There is a great variety of injuries that affect peripheral nerves derived from acquired or congenital degenerative diseases affecting the central nervous system that cause loss of sensorimotor functions. The objective of this work was to perform an end-to-side or side-to-side experimental axonal stereological study in order to compare volume density of axons, endouneuro and myelin sheath (and muscle mass) in peroneal and tibial nerves, with anastomosis contact from 0.25 cm to 0.50 cm. After approval of the Ethics Committe, 20 male Wistar rats were divided into four groups of five rats each (G1= end-to-side neurorrhaphy; G2= side-to-side neurorrhaphy of 0.25 cm; G3= side-to-side neurorrhaphy of 0 cm and G4= Control of normality). After 180 days, fragments of peroneal and tibial nerves were collected for histological and stereological study. In comparative stereological experimental study between neurorraphies, the volume density of axons, myelin sheath of tibial and fibular nerves, as well as the post-surgical muscle mass, remains the same in end-to-side and side-to-side neurorraphies, regardless of contact area of anastomosis. It can be inferred, as surgical repair options, both end-to-side neurorrhaphy to recover and prevents atrophy of the endplate as side-to-side neurorraphy that is independent of the distance between the nerve stumps.

Gran variedad de lesiones atingen a los nervios periféricos, derivadas de enfermedades adquiridas o degenerativas congénitas que afectan la parte central del sistema nervioso y que ocasionan pérdida de funciones sensoriomotoras. El objetivo de ese trabajo fue realizar un estudio experimental estereológico axonal post neurorrafias termino-lateral o latero-lateral para comparar densidad de volumen de axones, endoneuro y vaina de mielina (así como masa muscular) en nervios fibular y tibial, con unión de contacto entre 0,25 cm y 0,50 cm. Tras la aprobación del comité de ética, fueran utilizados 20 ratones machos de la raza Wistar divididos en cuatro grupos de 5 ratones cada uno (G1= Neurorrafia término lateral; G2= Neurorrafia latero lateral de 0,25 cm; G3= Neurorrafia latero lateral de 0,50 cm y G4= Control). Posteriormente, fragmentos de los nervios tibiales y fibulares fueron procesados para estudios histológicos y estereológicos. En el estudio experimental estereológico comparativo entre neurorrafias termino-lateral y latero-lateral, la densidad de volumen de axones, endoneuro y vaina de mielina de nervios tibial y fibular y también la masa muscular post quirúrgica se mantuvo equitativa, independientemente del área de unión de contacto. Podemos inferir como opciones de reparación quirúrgica, que el tratamiento de la neurorrafia termino-lateral y latero-lateral previnen la atrofia de placa motora, independiente de la distancia entre los muñones nerviosos.

Animals , Male , Rats , Neurosurgical Procedures/methods , Peroneal Nerve/pathology , Peroneal Nerve/surgery , Tibial Nerve/pathology , Tibial Nerve/surgery , Axons/pathology , Myelin Sheath/pathology , Nerve Regeneration , Peripheral Nerves/pathology , Peripheral Nerves/surgery , Rats, Wistar
Arq. neuropsiquiatr ; 70(9): 733-740, Sept. 2012. tab
Article in English | LILACS | ID: lil-649310


The physiopathology of symptoms and signs in multiple sclerosis (MS) is a less divulged topic albeit its importance in the patients' management. OBJECTIVE: It was to summarize the main biophysical and biochemical mechanisms which produce the clinical manifestations in MS. RESULTS: The mechanisms underpinning neurological deficits are described in the relapsing and in the progressive phases, stressing inflammatory and neurodegenerative components, especially demyelination, axonal damage and conduction impairment. Transient worsening based in Uhthoff's phenomenon, mechanisms producing positive symptoms, as paraesthesias and Lhermitte sign due to axonal hiperexcitability and ephaptic interactions, and development of cortical symptoms will also be addressed. The variety of processes leading to neural repair and functional recovery in the remitting phase is focused, as remyelination and adaptive changes due to neural plasticity. CONCLUSION: The awareness of mechanisms producing symptoms in MS emphasises the role of symptomatic and rehabilitation therapies in the improvement of patients' well-being.

A fisiopatologia dos sintomas e sinais na esclerose múltipla (EM) é um tópico pouco divulgado apesar da sua importância na abordagem dos doentes. OBJETIVO: Foi apresentar os principais mecanismos biofísicos e bioquímicos que produzem manifestações clínicas da EM. RESULTADOS: Descrevem-se os mecanismos subjacentes aos défices neurológicos nas fases de surto e progressivas, realçando as componentes inflamatória e neurodegenerativa, especialmente desmielinização, lesão axonal e alterações da condução. Serão igualmente referidos os sintomas transitórios explicados pelo fenômeno de Uhthoff, a produção de sintomas positivos, como as parestesias e o sinal de Lhermitte por hiperexcitabilidade axonal e interações efáticas, e o desenvolvimento de sintomas corticais. Apresentam-se os diversos processos de reparação neural e de recuperação funcional nas fases de remissão, como a remielinização e as alterações adaptativas por neuroplasticidade. CONCLUSÃO: O conhecimento dos mecanismos que produzem os sintomas da EM realça o papel das terapêuticas sintomáticas e de reabilitação na melhoria do bem-estar dos doentes.

Humans , Multiple Sclerosis/pathology , Multiple Sclerosis/physiopathology , Axons/pathology , Inflammation/pathology , Magnetic Resonance Imaging , Multiple Sclerosis, Relapsing-Remitting/pathology , Multiple Sclerosis, Relapsing-Remitting/physiopathology , Neuroglia/physiology , Neuronal Plasticity/physiology , Recovery of Function , Symptom Assessment
Arq. neuropsiquiatr ; 69(2b): 365-370, 2011. ilus, tab
Article in English | LILACS | ID: lil-588099


Epineural stitches are a means to avoid tension in a nerve suture. We evaluate this technique, relative to interposed grafts and simple neurorraphy, in a rat model. METHOD: Twenty rats were allocated to four groups. For Group 1, sectioning of the sciatic nerve was performed, a segment 4 mm long discarded, and epineural suture with distal anchoring stitches were placed resulting in slight tension neurorraphy. For Group 2, a simple neurorraphy was performed. For Group 3, a 4 mm long graft was employed and Group 4 served as control. Ninety days after, reoperation, latency of motor action potentials recording and axonal counts were performed. Inter-group comparison was done by means of ANOVA and the non-parametric Kruskal-Wallis test. RESULTS: The mean motor latency for the simple suture (2.27±0.77 ms) was lower than for the other two surgical groups, but lower than among controls (1.69±0.56 ms). Similar values were founding in both group 1 (2.66±0.71 ms) and group 3 (2.64±0.6 ms). When fibers diameters were compared a significant difference was identified between groups 2 and 3 (p=0.048). CONCLUSION: Good results can be obtained when suturing a nerve employ with epineural anchoring stitches. However, more studies are needed before extrapolating results to human nerve sutures.

A aproximação através de pontos epineurais é uma forma de se reduzir a tensão numa neurorrafia. Neste estudo esta técnica é avaliada através da sua comparação com a interposição de enxertos e neurorrafia simples num modelo experimental utilizando o rato. MÉTODO: Vinte ratos foram utilizados e divididos em 4 grupos. No Grupo 1, após a ressecção de 4 mm, os cotos do nervo foram aproximados através de pontos de ancoramento epineurais e suturados com tensão. No Grupo 2, uma neurorrafia simples foi realizada após secção do nervo. No Grupo 3, um enxerto de 4 mm foi utilizado para o reparo e o Grupo 4 foi utilizado como controle. Noventa dias após, os nervos foram novamente expostos e a medida da latência do potencial de ação motor e a contagem axonal foram realizados. A comparação entre os grupos foi realizada através da comparação entre as médias (ANOVA) e com o teste não-paramétrico de Kruskal-Wallis. RESULTADOS: A média da latência motora na sutura simples (2,27±0,77 ms) foi menor em relação aos outros dois grupos onde o nervo foi seccionado e reparado e maior que o grupo controle (1,69±0,56 ms). Resultados semelhantes foram identificados nos grupos 1 (2,66±0,71 ms) e 3 (2,64±0,6 ms). Uma diferença significativa diâmetros das fibras foi identificada quando comparados os grupos 2 e 3 (p=0,048). CONCLUSÃO: Resultados equiparáveis aos obtidos com enxerto podem ser obtidos quando a neurorrafia é realizada com pontos epineurais de ancoramento com tensão, mas estudos adicionais são necessários antes desses resultados serem extrapolados para o reparo de nervo em seres humanos.

Animals , Male , Rats , Axons , Nerve Regeneration/physiology , Peripheral Nerves/surgery , Suture Techniques , Axons/pathology , Axons/physiology , Electrophysiology , Models, Animal , Random Allocation , Tensile Strength
Article in English | WPRIM | ID: wpr-14303


Transcranial direct current stimulation (tDCS) is associated with enhancement or weakening of the NMDA receptor activity and change of the cortical blood flow. Therefore, repeated tDCS of the brain with cerebrovascular injury will induce the functional and histologic changes. Sixty-one Sprague-Dawley rats with cerebrovascular injury were used. Twenty rats died during the experimental course. The 41 rats that survived were allocated to the exercise group, the anodal stimulation group, the cathodal stimulation group, or the control group according to the initial motor function. Two-week treatment schedules started from 2 days postoperatively. Garcia, modified foot fault, and rota-rod performance scores were checked at 2, 9, and 16 days postoperatively. After the experiments, rats were sacrificed for the evaluation of histologic changes (changes of the white matter axon and infarct volume). The anodal stimulation and exercise groups showed improvement of Garcia's and modified foot fault scores at 16 days postoperatively. No significant change of the infarct volume happened after exercise and tDCS. Neuronal axons at the internal capsule of infarct hemispheres showed better preserved axons in the anodal stimulation group. From these results, repeated tDCS might have a neuroprotective effect on neuronal axons in rat stroke model.

Animals , Axons/pathology , Cerebral Cortex/physiology , Disease Models, Animal , Electric Stimulation , Motor Activity/physiology , Rats , Rats, Sprague-Dawley , Stroke/metabolism
Arq. bras. oftalmol ; 72(5): 622-625, set.-out. 2009. graf, tab
Article in English | LILACS | ID: lil-534179


PURPOSE: To compare the optical coherence tomography retinal nerve fiber layer and macular thickness measurements for detection of progressive axonal loss following acute traumatic optic neuropathy in a longitudinal study. METHODS: Three patients with unilateral traumatic optic neuropathy were evaluated sequentially after trauma. Macular and retinal nerve fiber layer thickness measurements were obtained using optical coherence tomography weekly for five weeks and around the twelfth week after trauma. RESULTS: All patients showed progressive macular and retinal nerve fiber layer thickness reduction. The mean retinal nerve fiber layer thickness on the first week was 114 μm and reduced sequentially over the first five weeks and was 46 μm on the twelfth week. For macular parameters, the mean average thickness on the first week was 248 μm and also reduced over the first five weeks and was 218 μm on the twelfth week. When compared to the initial measurement, macular thickness average reduction rate at the 12th week was 14 percent while peripapillary retinal nerve fiber layer thickness average reduction rate was 59 percent. CONCLUSIONS: Although both measurements reduce significantly after trauma, retinal nerve fiber layer thickness measurements show greater and faster retinal neural reduction if compared to macular thickness measurements in traumatic optic neuropathy.

OBJETIVO: Comparar as medidas da espessura da camada de fibras nervosas da retina e macular obtidas pela tomografia de coerência óptica na detecção da perda axonal progressiva após neuropatia óptica traumática aguda e durante o seguimento clínico. MÉTODOS: Três pacientes com neuropatia óptica traumática unilateral aguda foram avaliados sequencialmente após o trauma. Medidas da espessura macular e da camada de fibras nervosas da retina foram obtidas pela tomografia de coerência óptica semanalmente por 5 semanas consecutivas e ao redor da décima segunda semana após o trauma. RESULTADOS: Todos os pacientes apresentaram redução progressiva dos valores da espessura macular e da camada de fibras nervosas da retina. A espessura média da camada de fibras nervosas da retina foi de 114 μm na primeira semana e reduziu sequencialmente ao longo das primeiras cinco semanas e foi de 46 μm na décima segunda semana. Para parâmetros macular, a espessura média foi de 248 μm na primeira semana, e também reduziu ao longo das primeiras cinco semanas e foi de 218 μm na décima segunda semana. Quando comparado às medidas iniciais, a taxa de redução das médias da espessura macular foi 14 por cento na décima segunda semana após o trauma, enquanto que a taxa de redução das médias da espessura da camada de fibras nervosas da retina foi 59 por cento. CONCLUSÕES: Os valores da espessura da camada de fibras nervosas da retina apresentaram uma redução maior e mais rápida se comparada às medidas da espessura macular na neuropatia óptica traumática.

Adult , Female , Humans , Male , Young Adult , Axons/pathology , Macula Lutea/pathology , Optic Nerve Injuries/pathology , Optic Nerve/pathology , Disease Progression , Follow-Up Studies , Optic Nerve Injuries/complications , Tomography, Optical Coherence , Young Adult
Rev. chil. neuro-psiquiatr ; 47(1): 43-49, mar. 2009. ilus, tab
Article in Spanish | LILACS | ID: lil-554888


Delayed Hypoxic-isquemic Leucoencephalopathy described in 1976 by Ginsberg is a brain white matter demyelinization phenomenon that occurred days or weeks after a hypoxic-isquemic injury followed by a complete recovery of the episode. The pathogenesis process remains unknown. We describe a 48 year old woman with cervico-uterine cancer in palliative treatment with opoids. She enters the emergency room with a respiratory depression, a prolonged hypotension and confusion, that it was recovered. At admission exhibits a recurrent pneumonia. Two weeks later, in conditions of discharge, initiates with agitation in context with rapidly progressive decline cognition, with concordant lesions of Leucoencephalopathy defined in the Magnetic Resonance (MR) study The metabolic profile, the cerebrospinal fluid and the electroencephalogram allowed dismissing other etiologic hypothesis. In front to the suspicious of Ginsberg syndrome, she had normal levels of Arylsulfatase. This acute post-hypoxic demyelinization process has been pathogenic interpreted as an arylsulfatase deficiency. Although numerous cases develop with normal arylsulfatase and the experimental studies of hypoxia, has support the hypothesis of a central hypoxic axonopathy due to failing in axonal transport as the base of the demyelinization phenomenal.

La leucoencefalopatía hipóxico-isquémica retardada (EHIR), descrita por Ginsberg en el año 1976, es un fenómeno desmielinizante de la sustancia blanca cerebral, que se origina días o semanas después de un daño hipóxico-isquémico que había sido seguido de una recuperación completa del episodio. La patogenia del proceso no está completamente establecida. Se presenta una mujer de 48 años portadora de cáncer cérvicouterino, en tratamiento paliativo con opiáceos. Ingresa al Servicio de Urgencia por una depresión respiratoria, hipotensión prolongada y compromiso de conciencia, donde es recuperada. Se hospitaliza por una neumopatía intercúrrente. Dos semanas más tarde, estando en condiciones de alta, se inicia agitación psicomotora en el contexto de un deterioro cognitivo rápidamente progresivo, que el estudio de Resonancia Magnética (RM) definió como lesiones concordantes con una leucoencefalopatía. El perfil metabólico, el líquido cefalorraquídeo y el electroencefalograma, permitieron descartar otras hipótesis etiológicas. Frente a la sospecha de un síndrome de Ginsberg, los niveles de arilsulfatasa fueron normales. Este proceso desmielinizante agudo post-hipóxico, ha sido interpretado patogénicamente como un déficit de arilsulfatasa. Sin embargo, la existencia de numerosos casos que cursan con arilsulfatasa normal y los estudios experimentales de hipoxia, ha avalado la hipótesis de una axonopatía central hipóxica, atribuible a fallas del transporte axoplásmico, como base para el fenómeno desmielinizante.

Humans , Female , Middle Aged , Cerebrum/pathology , Hypoxia-Ischemia, Brain/complications , Psychomotor Agitation/etiology , Axons/pathology , Confusion/etiology , Cognition Disorders/etiology
Rev. chil. neuro-psiquiatr ; 47(1): 50-66, mar. 2009. ilus
Article in Spanish | LILACS | ID: lil-554889


Revision is made to 121 Chilean patients with progressive adult spastic paraparesis (PSPs) associated to HTLV-I. Epidemiologic, clinical, diagnosis and associated illnesses aspects are analyzed as well as the pathogenesis. The follow-up of patients during several years allowed defining the evolutional profile, establishing the causes of death and studying the virus' behavior. Pathogenesis hypothesis arose from the neuropathological search to define the mechanisms of damage supported on immunohystochemical studies. It was confirmed that the CNS illness is a degenerative process linked to a central axonopathy which expresses flaws in the axoplasmic transport, particularly affecting the corticospinal tracts, although there is a more extended myeloencephalic involvement. Furthermore, the virus is capable of producing a multisystemic illness that may simultaneously involve the nervous system; the hematological system; the exocrine glands; the hepatic, lung, muscular and bone parenchymas.

Se revisan las paraparesias espásticas progresivas del adulto (PEPAs) producidas por el HTLV-I, en 121 pacientes chilenos. Se analizan los aspectos epidemiológicos, clínicos, diagnósticos, las enfermedades asociadas, y la patogenia. El seguimiento de los pacientes durante varios años permitió definir el perfil evolutivo, establecer las causas de muerte y estudiar el comportamiento del virus. De los casos con anatomía patológica surgieron hipótesis, que han permitido definir mecanismos de daño, sustentados en estudios inmunohistoquímicos. Se pudo confirmar que la enfermedad del SNC es un proceso degenerativo, vinculado a una axonopatía central que expresa fallas del transporte axoplásmico, que afecta particularmente la vía corticoespinal, aunque existe un compromiso más extenso mielo-encefálico. Además, el virus es capaz de producir una enfermedad multisistémica, que puede comprometer simultáneamente el sistema nervioso, el sistema hematológico, las glándulas exocrinas, el parénquima hepático, pulmonar, muscular y óseo.

Humans , Male , Adolescent , Adult , Female , Middle Aged , HTLV-I Infections/complications , Paraparesis, Tropical Spastic/etiology , Paraparesis, Tropical Spastic/mortality , Paraparesis, Tropical Spastic/pathology , Axons/pathology , Cause of Death , Clinical Evolution , Chile/epidemiology , Follow-Up Studies , Paraparesis, Tropical Spastic/physiopathology
Article in English | WPRIM | ID: wpr-69280


BACKGROUND: The aim of this study was to evaluate the contribution of the proximal nerve stump, in end-to-side nerve repair, to functional recovery, by modifying the classic end-to-side neurorrhaphy and suturing the proximal nerve stump to a donor nerve in a rat model of a severed median nerve. METHODS: Three experimental groups were studied: a modified end-to-side neurorrhaphy with suturing of the proximal nerve stump (double end-to-side neurorrhaphy, Group I), a classic end-to-side neurorrhaphy (Group II) and a control group without neurorrhaphy (Group III). Twenty weeks after surgery, grasping testing, muscle contractility testing, and histological studies were performed. RESULTS: The grasping strength, muscle contraction force and nerve fiber count were significantly higher in group I than in group II, and there was no evidence of nerve recovery in group III. CONCLUSIONS: The contribution from the proximal nerve stump in double end-to-side nerve repair might improve axonal sprouting from the donor nerve and help achieve a better functional recovery in an end-to-side coaptation model.

Anastomosis, Surgical/methods , Animals , Axons/pathology , Forelimb , Hand Strength , Male , Median Nerve/pathology , Muscle Contraction , Muscle, Skeletal/physiopathology , Nerve Regeneration , Nerve Transfer/methods , Rats , Rats, Sprague-Dawley , Recovery of Function , Ulnar Nerve/pathology
Article in English | WPRIM | ID: wpr-76616


A subset of patients of amyotrophic lateral sclerosis (ALS) present with mutation of Cu/Zn superoxide dismutase 1 (SOD1), and such mutants caused an ALS-like disorder when expressed in rodents. These findings implicated SOD1 in ALS pathogenesis and made the transgenic animals a widely used ALS model. However, previous studies of these animals have focused largely on motor neuron damage. We report herein that the spinal cords of mice expressing a human SOD1 mutant (hSOD1-G93A), besides showing typical destruction of motor neurons and axons, exhibit significant damage in the sensory system, including Wallerian-like degeneration in axons of dorsal root and dorsal funiculus, and mitochondrial damage in dorsal root ganglia neurons. Thus, hSOD1-G93A mutation causes both motor and sensory neuropathies, and as such the disease developed in the transgenic mice very closely resembles human ALS.

Amyotrophic Lateral Sclerosis/enzymology , Animals , Axons/pathology , Disease Models, Animal , Ganglia, Spinal/pathology , Humans , Mice , Mice, Transgenic , Mitochondria/pathology , Motor Neurons/metabolism , Mutation , Nerve Degeneration/pathology , Sensory Receptor Cells/pathology , Spinal Cord/pathology , Superoxide Dismutase/genetics
Article in English | WPRIM | ID: wpr-150871


PURPOSE: To evaluate the relationship between optic disc and retinal nerve fiber layer (RNFL) measurements obtained with the optical coherence tomography (OCT) and the Heidelberg retina topography (HRT) in normal, normal tension glaucoma (NTG), and high tension glaucoma (HTG). METHODS: Normal, NTG and HTG subjects who met inclusion and exclusion criteria were evaluated retrospectively. One hundred seventy eyes of 170 patients (30 normal, 40 NTG, and 100 HTG) were enrolled. Complete ophthalmologic examination, HRT, OCT, and automated perimetry were evaluated. RESULTS: Disc area, cup area and cup/disc area ratio measured with HRT were significantly different between NTG and HTG (all p0.05). Mean deviation and corrected pattern standard deviation measured by automated perimetry was significantly correlated with mean and inferior RNFL thickness in both NTG and HTG (Pearson's r, p<0.05). Mean RNFL thickness/disc area ratio was significantly larger in HTG than NTG (35.21+/-18.92 vs. 31.30+/-10.91, p=0.004). CONCLUSIONS: These findings suggest that optic disc and RNFL damage pattern in NTG may be different from those of HTG.

Adult , Aged , Axons/pathology , Diagnostic Techniques, Ophthalmological , Female , Glaucoma, Open-Angle/diagnosis , Humans , Male , Middle Aged , Ocular Hypertension/diagnosis , Optic Disk/pathology , Optic Nerve Diseases/diagnosis , Visual Field Tests , Retinal Ganglion Cells/pathology , Retrospective Studies , Tomography, Optical Coherence , Visual Fields
Rev. méd. Chile ; 135(9): 1139-1146, sept. 2007. ilus, tab
Article in Spanish | LILACS | ID: lil-468202


Background: Human T lymphotropic virus type I is associated with tropical spastic paraparesis, that is a chronic and progressive disease which damages specially the cortiespinal tracts. The pathogenesis of this degenerative process remains unknown. Aim: To identify histopathological aspects that could suggest a pathogenic hypothesis we studied immunohistochemical features in spinal cords obtained from patients that died due to progressive spastic paraparesis. Patients and Methods: Five males and five females, who died between 1990 and 2000, with a mean age of 52 years and mean disease duration of 8.6, were studied. All had a complete clinical and virological diagnosis. Samples were obtained from the frontal motor cortex and spinal cord (cervical, dorsal and lumbar segments), were fixed in formol (10 percent), included in paraffin, and stained with Haematoxylin and Luxol-fast-blue. Immunohistochemical study was made with anti-neurofilament antibodies 1:100 (M0762, DAKO), anti-APP 1:20 (Rabbit Pre Amyloid protein 51-2700 ZYMED), anti-tau 1:100 (A0024DAKO) and anti-ubiquitine 1:50 (NCL UBIQm Novocastra). Results: All cases had demyelinization and axonal loss in the cortico-spinal tracts; distal and segmental demyelinization of Goll tract; axonal thickening, amyloid precursor protein deposits in the white matter; tau protein aggregation in the spinal cord oligodendrocytes; axonal ubiquitination of sensitive and motor tracts, and subcortical white matter. Neurona! injury was absent. Conclusions: The systematic damage of motor and sensitive tracts of the spinal-cord and the absence of neurona! damage, defines a degenerative process limited to axons. This central axonopathie could be caused by a disturbance of axoplasmic transport.

Adult , Aged , Female , Humans , Male , Middle Aged , Human T-lymphotropic virus 1 , Nerve Degeneration/pathology , Paraparesis, Tropical Spastic/pathology , Spinal Cord/pathology , Amyloid beta-Protein Precursor/metabolism , Axonal Transport/physiology , Axons/pathology , Axons/virology , Immunohistochemistry , Nerve Degeneration/virology , Polymerase Chain Reaction , Paraparesis, Tropical Spastic/virology , Staining and Labeling , Spinal Cord/virology , Ubiquitin/metabolism , tau Proteins/metabolism
Rev. bras. otorrinolaringol ; 72(6): 786-793, nov.-dez. 2006. ilus, tab, graf
Article in Portuguese | LILACS | ID: lil-441147


A paralisia facial periférica traumática constitui-se em afecção freqüente. OBJETIVO: estudo da regeneração pós-traumática do nervo facial em coelhos, por avaliação funcional histológica dos nervos traumatizados comparados aos normais contralaterais. METODOLOGIA: Vinte coelhos foram submetidos à compressão do tronco do nervo facial esquerdo e sacrificados após duas (grupo AL), quatro (BL) e seis (CL) semanas da lesão. A comparação entre os grupos foi feita pelas densidades total e parcial de axônios mielinizados. ESTUDO ESTATíSTICO: método de Tukey (p < 0,05). RESULTADOS: Houve recuperação funcional parcial após duas, e completa após cinco semanas. Na análise qualitativa, verificou-se em AL um padrão degenerativo, com maior processo inflamatório tecidual. Em BL, sinais de regeneração neural, praticamente completa em CL. Os nervos normais (N) apresentaram DT média de 15705,59 e DP média de 21800,75. O grupo BL revelou DT média de 10818,55 e DP média de 15340,56 e o CL, DT média de 13920,36 e DP média de 16589,15. BL obteve 68,88 por cento, e o grupo CL, 88,63 por cento da DT de N. N mostrou DP maior que os lesados; porém, esta não evidenciou diferença estatística entre BL e CL. A DT dos nervos revelou-se um método analítico mais fidedigno do que a DP estudada.

Posttraumatic facial paralysis is a frequent disease. This work studies posttraumatic regeneration of the facial nerve in rabbits. Functional and histological analysis compared injured and normal nerves on opposite sides. The left facial nerve trunk of twenty rabbits were subjectedto compression lesion, and sacrificed after two (subgroup AL), four (BL) and six (CL) weeks. Comparison between groups was made by analysing total and partial densities of myelinated axons. STATISTICAL ANALYSIS: Tukey Method (p<0.05). RESULTS:There was partial functional recovery after two weeks, and complete recovery after five weeks. Qualitative analysis demonstrated a degenerative pattern in the AL group, with an increased tissue inflammatory process. Evident regeneration signs were observed in the BL group, and almost complete regeneration was seen in the CL group. Normal nerves (N) had an average TD of 15705.59 and average PD of 21800.75. The BL group had an average TD of 10818.55 and an average PD of 15340.56. The CL group had an average TD of 13920.36 and an average PD of 16589.15. The BL group had an average TD of N equal to 68.88 percent, and the CL group had an average TD of N equal to 88,63 percent (statistically significant). N showed a significant higher PD than injured nerves. However, this was not statistically different between BL and CL subgroups. Nerve DT was a more reliable method than PD in this study.

Animals , Male , Rabbits , Axons/pathology , Facial Nerve Injuries/pathology , Facial Nerve/physiology , Myelin Sheath/pathology , Nerve Regeneration/physiology , Axons/physiology , Cell Count , Disease Models, Animal , Facial Nerve Injuries/physiopathology , Myelin Sheath/physiology
Arq. neuropsiquiatr ; 64(3a): 609-612, set. 2006.
Article in English, Portuguese | LILACS | ID: lil-435598


Bariatric surgery is frequently indicated in the treatment of morbid obesity. Previously unreported complications have been associated to this surgery; among them, neurological complications have gained attention. We report the case of a 25-year-old man submitted to gastric surgery for treatment of morbid obesity who developed, two months after surgery, acute proximal weakness in lower limbs. The electroneuromyography revealed axonal peripheral polyneuropathy with predominant proximal involvement. After treatment with immunoglobulin and vitamin supplementation, rapid clinical and neurophysiologic recovery was observed. We describe the clinical and electroneuromyographic features of this case, stressing the difficulty of initial diagnosis, particularly in the differential diagnosis with Guillain-Barré syndrome. We discuss the importance of nutritional follow-up and the eventual indication of routine vitamin supplementation in these patients.

A cirurgia bariátrica é freqüentemente indicada no tratamento da obesidade mórbida. Complicações previamente não relatadas têm sido associadas a essa cirurgia; dentre estas, as complicações neurológicas têm recebido destaque. Relatamos o caso de um homem de 25 anos de idade submetido a cirurgia gástrica para tratamento de obesidade mórbida que desenvolveu, dois meses após a cirurgia, fraqueza de predomínio proximal nos membros inferiores, de instalação aguda. A eletroneuromiografia demonstrou polineuropatia periférica axonal nos membros inferiores, de predomínio proximal. Após tratamento com imunoglobulina e suplementação vitamínica, apresentou rápida melhora clínica e neurofisiológica. Descrevemos as características clínicas e eletroneuromiográficas desse caso, destacando a dificuldade diagnóstica inicial, particularmente com relação ao diagnóstico diferencial com síndrome de Guillain-Barré. Discutimos a importância de acompanhamento nutricional e a eventual indicação de suplementação vitamínica de rotina nesses pacientes.

Humans , Male , Adult , Axons/pathology , Bariatric Surgery/adverse effects , Obesity, Morbid/surgery , Polyneuropathies/diagnosis , Polyneuropathies/etiology , Acute Disease , Diagnosis, Differential , Electromyography , Guillain-Barre Syndrome/diagnosis , Polyneuropathies/drug therapy
Arq. bras. oftalmol ; 69(4): 531-537, jul.-ago. 2006. tab
Article in Portuguese, English | LILACS | ID: lil-435738


OBJETIVO: Comparar a capacidade do polarímetro de varredura a laser (GDx), do tomógrafo de coerência óptica (OCT) 1 e do Stratus-OCT em diferenciar olhos normais de olhos com atrofia em banda do nervo óptico e hemianopsia temporal. MÉTODOS: Vinte e três olhos de pacientes com atrofia em banda do nervo óptico e 23 olhos de indivíduos normais foram incluídos em estudo prospectivo observacional caso-controle. Todos foram submetidos à análise da camada de fibras nervosas retiniana (CFNR) utilizando GDx, OCT-1 e Stratus-OCT. As médias dos valores obtidos em cada aparelho foram comparadas entre olhos com atrofia em banda e controles normais. Curvas ROC (receiver operating characteristic) e sensibilidade para especificidades fixas (80 por cento e 95 por cento) foram calculadas para cada parâmetro produzido pelos três instrumentos e comparadas entre si. RESULTADOS: Quando comparados aos indivíduos normais, os resultados dos pacientes referentes à camada de fibras nervosas retiniana (média global e quatro quadrantes estudados) foram significativamente menores (p<0,05) em todos os aparelhos estudados, com exceção do parâmetro referente ao setor temporal quando avaliado pelo GDx. A comparação das áreas sob a curva ROC (AROC) dos parâmetros referentes aos três aparelhos mostrou valores significativamente maiores para o Stratus-OCT quando comparados ao OCT-1 na média global e no setor temporal. O Stratus-OCT foi significativamente mais sensível do que o GDx na média global e nos quadrantes temporal, nasal e inferior. Por sua vez, o OCT-1 foi superior ao GDx na discriminação dos defeitos apenas no quadrante temporal, não mostrando diferença significativa na média global e nos demais quadrantes. Os três aparelhos mostraram capacidade semelhante na identificação dos defeitos referentes ao quadrante superior. CONCLUSÃO: O Stratus-OCT demonstrou a maior capacidade em diferenciar olhos com atrofia em banda do nervo óptico de olhos normais embora todos os três aparelhos consigam...

PURPOSE: To compare the abilitiy of scanning laser polarimetry (GDx), optical coherence tomography (OCT) 1 and Stratus- optical coherence tomography to discriminate between healthy eyes and eyes with band atrophy of the optic nerve and temporal hemianopsia. METHODS: Twenty-three eyes with band atrophy of the optic nerve and 23 eyes from healthy subjects were included in this observational prospective case-control study. All eyes underwent retinal nerve fiber layer (RNFL) thickness analysis using GDx, optical coherence tomography-1 and Stratus-optical coherence tomography. Mean values obtained with each equipment were compared between band atrophy and normal eyes. Receiver operating characteristic (ROC) curves and sensitivities at fixed specificities (80 percent e 95 percent) were calculated for each parameter calculated with each equipment and compared. RESULTS: When compared with healthy subjects, the parameters corresponding to the global average as well as each of the four quadrant retinal nerve fiber layer thickness in eyes with band atrophy were significantly smaller (p<0.05), than in normal eyes, with the exception of GDx's temporal thickness parameter. Comparison of the areas under ROC curves (AUCs) of the parameters from the three equipments revealed significantly greater values for the Stratus-OCT when compared to the OCT-1 in the global average and in the temporal quadrant thickness measurement. Stratus-OCT was significantly more sensitive than GDx in the global average as well as in the temporal, nasal and inferior quadrant. OCT-1 was superior to GDx only in the temporal quadrant. All three equipments revealed a similar ability to identify retinal nerve fiber layer reduction in the superior quadrant. CONCLUSIONS: The Stratus OCT showed the best ability to discriminate between eyes with band atrophy of the optic nerve and healthy eyes although all three equipments were able do identify most of the abnormal eyes. OCT-1 was inferior to Stratus-OCT and...

Humans , Male , Female , Middle Aged , Axons/pathology , Diagnostic Techniques, Ophthalmological , Optic Atrophy/diagnosis , Tomography, Optical Coherence/methods , Case-Control Studies , Lasers , Sensitivity and Specificity , Visual Field Tests
Medicina (B.Aires) ; 66(5): 472-485, 2006. ilus
Article in Spanish | LILACS | ID: lil-451719


La esclerosis múltiple (EM) ha sido considerada clásicamente como una enfermedad desmielinzante. Si bien el compromiso neurodegenerativo fue previamente descripto, sólo recientemente ha sido enfatizado. Por estudiosos recientes se ha identificado la degeneración axonal como el mayor determinante de discapacidad neurológica irreversible en pacientes con EM. El daño axonal se inicia tempranamente y permanece silente durante años, la discapacidad neurológica se desarrolla cuando se alcanza cierto umbral de pérdida axonal y los mecanismos de compensación se agotan. Se han propuesto tres hipótesis para explicar el daño axonal: 1) El daño es causado por un proceso inflamatorio, 2) Existe una excesiva acumulación de Ca2+ intra-axonal, 3) Los axones desmienlinizados evolucionan a un proceso degenerativo producto de la falta de soporte trófico provisto por la mielina o células formadoras de mielina. Si bien la EM fue tradicionalmente considerada como una enfermedad de la sustancia blanca, el proceso de desmielinización tambiém ocurre en la corteza cerebral

The concept of multiple sclerosis (MS) as a demyelinating disease is deeply ingrained. Although the existence of a neurodegenerative component has always been apparent, it has only recently become emphasized. Thus, in recent years several studies have identified axonal degeneration as the major determinant of irreversible neurological disability in patients with MS. Axonal injury begins at disease onset and remains clinically silent for many years; irreversible neurological disability develops when a threshold of axonal loss is reached and CNS compensatory mechanisms are exhausted. The precise mechanisms of axonal loss are poorly understood, and three hypotheses have been proposed: 1) The damage is caused by an inflammatory process, 2) There is an excessive accumulation of intra-axonal Ca2+, 3) Demyelinated axons undergo degeneration due to lack of trophic support by myelin, or myelin forming cells. Although MS has traditionally been regarded as a disease of white matter, demyelination can also occur in the cerebral cortex. Cortical lesions exhibit neuronal injury represented by dendritic and axonal transection as well as neuronal apoptosis. Because conventional nuclear magnetic resonance (NMR) is limited in its ability to provide specific information about axonal pathology in MS, new techniques such as, diffusion-weighted MRI, proton magnetic resonance spectroscopy, functional MRI, as well as novel techniques designed to measure atrophy have been developed to monitor MS evolution. Recognition that MS is in part a neurodegenerative disease should trigger critical rethinking on the pathogenic mechanisms of this disease and provides new targets for a rational treatment

Humans , Axons/pathology , Multiple Sclerosis/pathology , Nerve Degeneration/pathology , Apoptosis/physiology , Axons/metabolism , Encephalomyelitis, Autoimmune, Experimental/metabolism , Encephalomyelitis, Autoimmune, Experimental/pathology , Encephalomyelitis, Autoimmune, Experimental/physiopathology , Genes, MHC Class I/physiology , Magnetic Resonance Spectroscopy , Multiple Sclerosis/metabolism , Multiple Sclerosis/physiopathology , Nerve Degeneration/metabolism , Nerve Degeneration/physiopathology , Retinal Ganglion Cells/metabolism , Retinal Ganglion Cells/parasitology , Retinal Ganglion Cells/pathology
Yonsei Medical Journal ; : 908-916, 2004.
Article in English | WPRIM | ID: wpr-203761


The biochemical factors related to moderation of secondary or delayed damage to the central nervous system (CNS) remain undefined. We have recently demonstrated that the weight- drop induced moderate diffuse axonal injury (mDAI) in rats causes a rapid decline in serum ionized magnesium (Mg2+) and a significant increase in the amount of serum ionized calcium (Ca2+) relative to Mg2+ (Ca2+/ Mg2+). For three hours, serum Mg2+ levels remained significantly depressed at 76% of preinjury values (p 0.05). Head trauma resulted in a small decrease of Ca2+ (about 10%), but a significant increase in the amount of Ca2+/Mg2+ (mean value in control group: in injured group for 3 hours after trauma =4.65 +/-0.012 : 5.69 +/-0.015, p< 0.05) was observed. In order to further investigate the relationship between Mg2+ and brain injury, the effect of Mg2+ treatment on posttraumatic histological changes (apoptotic changes) was examined following the weight-drop induced brain injury. At 30 min postinjury, animals treated with MgSO4 (750micro Ml/kg) showed significant improvements of apoptotic changes when compared to the control group (54.8 +/- 1.7, 51.5 +/- 3.2 at 12, 24 h in control group, 24.8 +/- 2.6, 20.5 +/- 1.4 at 12, 24 h in treated group, p< 0.05). The early decline in serum Mg2+ and the increase in the amount of Ca2+/Mg2+ immediately following brain trauma uncovered by these findings suggest that they may be a critical factor in the development of irreversible tissue injury. If this proves to be the case, treatment with MgSO4 may be effective in improving histological findings following experimental traumatic brain injury in rats.

Animals , Apoptosis/drug effects , Axons/pathology , Brain Injuries/blood , Calcium/blood , Magnesium/blood , Rats , Rats, Sprague-Dawley
Article in English | WPRIM | ID: wpr-20642


Although methylprednisolone (MP) is the standard of care in acute spinal cord injury (SCI), its functional outcome varies in clinical situation. Recent report demonstrated that MP depresses the expression of growth-promoting neurotrophic factors after acute SCI. The present study was designed to investigate whether continuous infusion of brain-derived neurotrophic factor (BDNF) after MP treatment promotes functional recovery in severe SCI. Contusion injury was produced at the T10 vertebral level of the spinal cord in adult rats. The rats received MP intravenously immediately after the injury and BDNF was infused intrathecally using an osmotic mini-pump for six weeks. Immunohistochemical methods were used to detect ED-1, Growth associated protein-43 (GAP-43), neurofilament (NF), and choline acethyl transferase (ChAT) levels. BDNF did not alter the effect of MP on hematogenous inflammatory cellular infiltration. MP treatment with BDNF infusion resulted in greater axonal survival and regeneration compared to MP treatment alone, as indicated by increases in NF and GAP-43 gene expression. Adjunctive BDNF infusion resulted in better locomotor test scores using the Basso-Beattie-Bresnahan (BBB) test. This study demonstrated that continuous infusion of BDNF after initial MP treatment improved functional recovery after severe spinal cord injury without dampening the acute effect of MP.

Animals , Anti-Inflammatory Agents/pharmacology , Axons/pathology , Brain-Derived Neurotrophic Factor/metabolism , Choline O-Acetyltransferase/metabolism , Female , GAP-43 Protein/metabolism , Gene Expression Regulation , Immunohistochemistry , Methylprednisolone/metabolism , Osmosis , Rats , Rats, Sprague-Dawley , Reverse Transcriptase Polymerase Chain Reaction , Spinal Cord/pathology , Spinal Cord Injuries/pathology , Time Factors