Progress in application of adult endogenous neurogenesis in brain injury repair / 生理学报

Persistent neurogenesis exists in the subventricular zone (SVZ) of the ventricles and the subgranular zone (SGZ) of the dentate gyrus of the hippocampus in the adult mammalian brain. Adult endogenous neurogenesis not only plays an important role in the normal brain function, but also has important significance in the repair and treatment of brain injury or brain diseases. This article reviews the process of adult endogenous neurogenesis and its application in the repair of traumatic brain injury (TBI) or ischemic stroke, and discusses the strategies of activating adult endogenous neurogenesis to repair brain injury and its practical significance in promoting functional recovery after brain injury.

Impairment induction by axotomy in motor functional and histological anterior horn of spinal cord structure / Inducción del deterioro por axotomía en la estructura motora funcional e histológica del asta anterior de la médula espinal

We have surveyed the motor changes in rats subjected to sciatic nerve axotomy. The rats were divided into two groups, each one consisting of ten animals, which underwent the following intervention: The first group (control): healthy rats without any injuries and experimental group: rats with injured sciatic nerve without treatment. at 12 weeks, the L4 and L5 spinal cord segments were removed. We evaluated nerve function using muscle electromyography (EMG) activity and sciatic function index (SFI) simultaneously with histological spinal cord analyses by stereological methods at 12 week. After nerve injury presented gross locomotor deficits at week 12. We also found that the volume of the anterior horn of spinal cord and total number of motor neurons were decreased after nerve axotomy (p<0.05). In conjunction, these results indicate that peripheral nerve injuries have more severe consequences on hind limb motor output.

En este estudio se examinaron los cambios motores en ratas sometidas a axotomía del nervio ciático. Las ratas se dividieron en dos grupos diez animales. El primer grupo (control) eran ratas sanas sin lesiones, y el grupo experimental consistió en ratas con nervio ciático lesionado sin tratamiento. A las 12 semanas, los segmentos de la médula espinal L4 y L5 fueron removidos. Se evaluó la función nerviosa mediante electromiografía muscular (EMG) y el índice de función ciática (IFC), simultáneamente con análisis histológicos de la médula espinal mediante métodos estereológicos. A las 12 semanas de la lesión nerviosa presentó déficit locomotor grueso. Además, se observó que el volumen del asta anterior y el número total de neuronas motoras disminuyeron después de la axotomía nerviosa (P <0,05). En conjunto, estos resultados indican que las lesiones de los nervios periféricos determinan graves consecuencias de la función motora de los miembros posteriores.

Daño medular espinal: tratamiento y posibles usus de la terapia celular / Spinal cord injury: treatment and possible uses of stem cells

El daño medular espinal, representa la principal causa de parálisis (total o parcial), que se acompaña de secuelas irreversibles y de gran impacto negativo para el paciente, entorno familiar y laboral. Con el advenimiento y avances en tecnología, técnicas de inmunohistoquímica, citología y bioingeniería, se han podido desarrollar numerosos estudios a nivel experimental, dirigidos a la recuperación de la función vertebro-espinal, con una inmensa gama de resultados, que sirven de asiento a futuras investigaciones en seres humanos. En su mayoría, evalúan funciones motoras y sensitivas durante las 3 fases de la lesión espinal. Para ello se emplean técnicas de implantación de células madre (de origen alogénico, autólogo o xenogénico) a través de la inyección intratecal o directa en parénquima nervioso. Los resultados a nivel experimental son alentadores; sin embargo, aún queda mucho por dilucidar en torno a la formación de la cicatriz glial, de los factores inductores que se expresan y su repercusión en humanos. Las directrices actuales en el tratamiento de la lesión espinal, incluyen desde mejoras en las técnicas de inmovilización y traslado pre-hospitalario del paciente lesionado espinal, pasando por el empleo de fármacos (Esteroides, Lazaroides, Calcio antagonistas, diuréticos osmóticos, etc.), hasta el uso de estimulación cortical, epidural y nanoimplantes medulares, así como la aplicación de exoesqueletos y de la Terapia Celular. En este artículo se reúnen los resultados de la revisión de estudios con más de 21mil publicaciones (hasta octubre del 2017), donde se han empleado células madre para tratar la lesión medular espinal (traumática)(AU)

Spinal cord damage represents the main cause of paralysis (total or partial), which is accompanied by irreversible sequelae and a high negative impact on the patient, family and work environment. With the advent and advances in technology, techniques of immunohistochemistry, cytology and bioengineering, numerous experimental studies have been developed, aimed at recovering vertebro-spinal function, with an immense range of results, which serve as a seat for future investigations in human beings. In their majority, they evaluate motor and sensory functions during the 3 phases of the spinal injury. For this purpose, implantation techniques of stem cells (of allogeneic, autologous or xenogenic origin) are used through intrathecal or direct injection in nervous parenchyma. The results at the experimental level are encouraging; However, much remains to be elucidated about the formation of the glial scar, the inducing factors that are expressed and their impact on humans. The current guidelines in the treatment of spinal injury include improvements in the techniques of immobilization and pre-hospital transfer of the injured spinal patient, through the use of drugs (steroids, lazaroids, calcium antagonists, osmotic diuretics, etc.) up to the use of cortical stimulation, epidural and spinal nanoimplantation, as well as the application of exoskeletons and Cell Therapy. This article brings together the results of the review of studies with more than 21 thousand publications (until October 2017), where stem cells have been used to treat spinal cord injury (traumatic)(AU)

Transitional cell carcinoma of urinary bladder with metastasis in lumbar vertebrae and spinal cord compression in an ocelot(Leopardus pardalis) / Carcinoma de células de transição de bexiga urinária com metástase em vértebras lombares e compressão de medula espinhal em uma jaguatirica (Leopardus pardalis)

This paper reports a case of nonpapillary and infiltrative transitional cell carcinoma (TCC) of the urinary bladder with metastasis of lumbar vertebrae and spinal cord compression in an adult female ocelot (Leopardus pardalis), from the Mato Grosso state, Brazil. The ocelot had pelvic limb paralysis and skin ulcers in the posterior region of the body and was submitted to euthanasia procedure. At necropsy was observed a multilobulated and irregular shaped, yellowish to white nodule in the urinary bladder. The nodule had a soft consistency and arised from the mucosa of the urinary bladder extending throughout the muscular layers and the serosa. Nodules of similar appearance infiltrating the vertebral column the at L6 and L7 vertebrae with corresponding spinal canal invasion were also observed. The histological evaluation showed epithelial neoplastic proliferation in the urinary bladder with characteristics of nonpapillary and infiltrative TCC, with positive immunohistochemical staining for pancytokeratin, and strong immunostaining for cytokeratin of low molecular weight, and weak or absent labeling for high molecular weight cytokeratin. This is the first report of TCC of urinary bladder in ocelot in Brazil...

O presente trabalho relata um caso de carcinoma de células de transição (TCC) da bexiga urinária com metástase em vértebras lombares e compressão da medula espinhal em uma jaguatirica fêmea adulta (Leopardus pardalis), no estado do Mato Grosso. A jaguatirica manifestava paralisia de membros pélvicos e úlceras de decúbito na região posterior do corpo e foi submetida a eutanásia. Na necropsia observou-se um nódulo multilobulado e irregular, brancoamarelado na bexiga urinária, de consistência macia com origem na mucosa vesical e que se estendia às camadas musculares e à serosa. Nódulos de aspecto semelhante infiltrando as vértebras L6 e L7 e invasão do canal vertebral correspondente. No exame histológico foi observada proliferação neoplásica na bexiga urinária com com características de TCC não papilar e infiltrativo, com marcação imuno-histoquímica positiva para pancitoqueratina, forte marcação para citoqueratina de baixo peso molecular e fraca ou inexistente para citoqueratina de alto peso molecular. Este é o primeiro relato de TCC em bexiga urinária de jaguatirica no Brasil...

Doenças neurológicas em cães atendidos no Hospital Veterinário da Universidade Federal de Santa Maria, RS: 1.184 casos (2006-2013) / Neurological diseases in dogs examined at the Veterinary Teaching Hospital of the Federal University of Santa Maria, RS: 1.184 cases (2006-2013)

Foi realizado um estudo retrospectivo de cães atendidos no Serviço de Neurologia (SN) do Hospital Veterinário Universitário (HVU) da Universidade Federal de Santa Maria (UFSM), de 2006 a 2013, com o objetivo de identificar e caracterizar a idade, a raça, o sexo e as doenças neurológicas e classificá-las de acordo com a região anatômica e o acrônimo DINAMIT-V. Foram avaliadas 1.277 fichas neurológicas de cães e obtidas as informações para inclusão no estudo em 1.184 delas, sendo o diagnóstico confirmado em 525 cães (44,4%) e presuntivo em 659 (55,6%). A raça mais frequente foi Dachshund (28,7%), seguida dos cães sem raça definida. Os locais mais afetados foram medula espinhal entre T3-L3 (40,9%) e tálamo-córtex (17,5%). A maioria dos cães foi diagnosticada com doença degenerativa (49%), sendo a doença do disco intervertebral a mais observada, seguida das doenças inflamatórias/infecciosas (16,6%). Pode se concluir que a maior prevalência das doenças neurológicas de cães envolve a medula espinhal e o tálamo-córtex, sendo as degenerativas as mais frequentes e os dados obtidos podem auxiliar em futuros estudos sobre a frequência e a distribuição das principais doenças neurológicas em cães.

A retrospective study including dogs with neurological disease was conducted at the Service of Neurology (SN) of the Veterinary Teaching Hospital, Universidade Federal de Santa Maria (UFSM) from 2006 to 2013, with the objective to identify and characterize age, breed, sex and to neurological diseases, and classify them accordingly to the anatomical region and DINAMIT-V acronym. There were evaluated 1,277 neurological records of dogs and obtained the information for inclusion in the study in 1,184 of them being the diagnosis confirmed in 525 (44.4%) and presumptive in 659 dogs (55.6%). The most common breed was Dachshund (28.7%), followed by mixed breed. The most affected sites were the spinal cord between T3-L3 (40.9%) and thalamus-cortex (17.5%). Most dogs were diagnosed with degenerative disorders (49%), being intervertebral disk disease the most observed, followed by inflammatory/infectious diseases (16.6%). It can be concluded that the higher prevalence of neurological disorders in dogs involve the spinal cord and thalamus-cortex, with the most frequent being degenerative and the data obtained may assist future studies associated with frequency and distribution of the main neurological diseases in dogs.

Diagnóstico diferencial das lesões inflamatórias e infecciosas do cone medular utilizando a ressonância magnética / Magnetic resonance imaging in the differential diagnosis of infectious and inflammatory conus medullaris lesions

The conus medullaris is frequently affected by inflammatory and infectious lesions which many times are hardly differentiated because of the similarity of their clinical history and physical examination among the different etiologies. Magnetic resonance imaging presents high sensitivity in the detection of these lesions and plays a relevant role in the diagnosis as well as in the evolutive control of the condition. The present pictorial essay with selected cases from the archives of the authors' institution is aimed at demonstrating imaging findings which might help in the diagnosis of a specific etiology amongst inflammatory an infectious conditions and in the differentiation with diseases of neoplastic and vascular etiologies, for example. Findings such as enhancement pattern, presence of cysts, edema and involvement of other regions of the central nervous system are important for this differentiation, and may define a specific etiology as associated with clinical and laboratory tests findings.

O cone medular é frequentemente acometido por lesões de etiologia inflamatória e infecciosa, muitas vezes de difícil diferenciação devido a história clínica e exame físico semelhantes entre as diversas entidades. A ressonância magnética apresenta alta sensibilidade na detecção de lesões no cone medular e tem importante papel no diagnóstico e controle evolutivo. Este ensaio iconográfico com casos selecionados dos arquivos do nosso serviço tem como objetivo demonstrar achados de imagem que possam auxiliar no diagnóstico de uma etiologia específica entre as doenças inflamatórias e infecciosas e na diferenciação com doenças de outras etiologias como neoplasias e causas vasculares. Características como padrão de realce, presença de cistos, edema, além do acometimento de outras regiões do sistema nervoso central são importantes para esta diferenciação, podendo definir uma etiologia específica quando associadas ao quadro clínico e laboratorial.

Pré-condicionamento isquêmico e monitorização da função medular na abordagem da aorta torácica descendente / Ischemic preconditioning and spinal cord function monitoring in the descending thoracic aorta approach

OBJETIVOS: Avaliar a eficácia do pré-condicionamento isquêmico (PI) agudo, guiado por potenciais evocados somatossensoriais (PESS), como método de proteção medular em cães e analisar o valor dos PESS na monitorização da função medular. MÉTODOS: Foram utilizados 28 cães submetidos à isquemia medular obtida pelo pinçamento da aorta torácica descendente. No grupo C45, o tempo de oclusão aórtica foi de 45 min (n = 7); no grupo PI45, os cães foram submetidos ao PI antes do pinçamento aórtico por 45 min (n = 7). No grupo C60, os cães foram submetidos a 60 min de oclusão aórtica (n = 7) e no grupo PI60, os cães foram submetidos ao PI, seguido pelo pinçamento aórtico por 60 min. Os ciclos de PI foram determinados pelas alterações dos PESS. RESULTADOS: Os índices de Tarlov dos grupos pré-condicionados foram significativamente melhores que os dos grupos de controle (p = 0,005). Observou-se paraplegia em três cães do C45 e em seis do C60, enquanto todos os cães do PI45 permaneceram neurologicamente normais, assim como quatro do grupo PI60. Houve correlação entre o tempo de recuperação dos PESS após a reperfusão aórtica e o estado neurológico pós-operatório (p = 0,011), com sensibilidade e especificidade de 0,75 e 0,83, respectivamente. CONCLUSÃO: O PI agudo repetitivo, baseado na monitorização do PESS, induziu proteção à isquemia medular causada pelo pinçamento aórtico prolongado. A monitorização do PESS parece ser um bom método de detecção precoce do comprometimento isquêmico medular.

OBJECTIVES: To evaluate the effectiveness of acute ischemic preconditioning (IP), based on somatosensory evoked potentials (SSEP) monitoring, as a method of spinal cord protection and to asses SSEP importance in spinal cord neuromonitoring. METHODS: Twenty-eight dogs were submitted to spinal cord ischemic injury attained by descending thoracic aorta cross-clamping. In the C45 group, the aortic cross-clamping time was 45 min (n=7); in the IP45 group, the dogs were submitted to IP before the aortic cross-clamping for 45 min (n=7). In the C60 group, the dogs were submitted to 60 min of aortic cross-clamping (n=7), as in the IP60 group that was previously submitted to IP. The IP cycles were determined based on SSEP changes. RESULTS: Tarlov scores of the IP groups were significantly better than those of the controls (p = 0.005). Paraplegia was observed in 3 dogs from C45 and in 6 from C60 group, although all dogs from IP45 group were neurologically normal, as 4 dogs from IP60. There was a significant correlation between SSEP recovery time until one hour of aortic reperfusion and the neurological status (p = 0.011), showing sensitivity of 75 percent and specificity of 83 percent. CONCLUSION: Repetitive acute IP based on SSEP is a protection factor during spinal cord ischemia, decreasing paraplegia incidence. SSEP monitoring seems to be a good neurological injury assessment method during surgical procedures that involve spinal cord ischemia.

Increased phosphorylation of caveolin-1 in the spinal cord of irradiated rats

Phosphorylation of caveolin-1 occurs during cell activation by various stimuli. In this study, the involvement of caveolin-1 in an irradiation injured spinal cord was examined by analyzing the phosphorylation of caveolin-1 in the spinal cord of rats after irradiation with a single dose of 15 Gray from a (60)Co gamma-ray source at 24 h post-irradiation (PI). A Western blot analysis showed that the phosphorylated form of caveolin-1 (p-caveolin-1) was expressed constitutively in the normal spinal cords and was significantly higher in the spinal cord of irradiated rats at 24 h PI. The increased expression of ED1, which is a marker of activated microglia/macrophages, was matched with that of p-caveolin-1. In the irradiated spinal cords, there was a higher level of p-caveolin-1 immunoreactivity in the isolectin B4-positive microglial, ependymal, and vascular endothelial cells, in which p-caveolin-1 was weakly and constitutively expressed in the normal control spinal cords. These results suggest that total body irradiation induces activation of microglial cells in the spinal cord through the phosphorylation of caveolin-1.

Spinal cord regeneration: the action of neurotrophin-3 in spinal cord injury in rats

OBJECTIVE: For many years, it was believed that medullary regeneration could not occur, although currently there are many trials using neurotrophic factors, stem cells, fetal medulla grafts, peripheral nerve grafts, and antibodies against myelin-associated proteins that demonstrate the existence of the possibility of spinal cord regeneration. The purpose of this study was to investigate the action of neurotrophin-3, a novel neurotrophic factor. METHODS: The New York University impactor, a standardized device for delivery of spinal cord injuries was used on 33 rats, which were divided into 2 groups: a control group receiving distilled water intraperitoneally and a treatment group receiving neurotrophin-3 intraperitoneally. RESULTS: Using the Basso, Beattie, and Bresnahan scale, the locomotor recovery curve for the neurotrophin-3 treated group was superior to that of the control group (P < 0.05); the administration of neurotrophin-3 was associated with the absence of deaths, while the control group showed a 28.5 percent (P = 0.026) mortality rate. Other parameters (hematuria rate and histological analysis) showed no significant differences. CONCLUSIONS: Based on these results, it appears that a strong relationship exists between the use of neurotrophin-3 in rats with spinal cord injury and better functional recovery.

OBJETIVO: Por muitos anos acreditou-se que a regeneração medular não fosse factível. Atualmente porém, existem várias experiências utilizando fatores neurotróficos, células troncos, enxerto de medula fetal, enxerto de nervo periférico e anticorpos contra proteínas associadas a mielina que sugerem o contrário. Esta pesquisa estudou a ação de um dos mais novos neurotróficos, o Neurotrophin-3. MÉTODOS: As lesões medulares foram realizadas através do New York University impator, método experimental de produção de lesão medular padronizada. Foram utilizados 33 ratos divididos em 2 grupos. Um grupo controle com administração intraperitoneal de água destilada e um grupo tratamento, tratado com Neurotrophin-3 por via intraperitoneal. RESULTADOS: Observamos que a curva de recuperação locomotora, segundo a escala de Basso, Beattie e Bresnahan, do grupo Neurotrophin-3 foi superior à do grupo controle (p < 0,05); a administração de Neurotrophin-3 determinou ausência de mortes no grupo tratamento, enquanto o grupo controle apresentou taxa de mortalidade de 28,5 por cento (p = 0,026). Os outros parâmetros (taxa de hematúria e análise histológica) não apresentaram diferenças estatisticamente significantes. CONCLUSÕES: Existe forte relação entre a aplicação de Neurotrophin-3 em ratos com lesão medular e melhor recuperação funcional.

Reflex Movements in Patients with Brain Death: A Prospective Study in A Tertiary Medical Center

Reflex movements have been reported to occur in up to 75% of brain-dead patients, but this issue has not been addressed in Korea. The patients admitted to our hospital who met the criteria for brain death were enrolled between March 2003 and February 2005. The frequency and type of reflex movements in these patients were evaluated prospectively using a standardized protocol. Brain death was determined according to the guideline of Korean Medical Association. Of 26 patients who were included, five (19.2%) exhibited reflex movements such as the pronation-extension reflex, abdominal reflex, flexion reflex, the Lazarus sign, and periodic leg movements. This finding suggests that the frequency of spinal reflex movements is not rare and the awareness of these movements may prevent delays in brain-dead diagnosis and misinterpretations.

Involuntary jerking of lower half of the body (spinal myoclonus).

A 55 years old, hypertensive, diabetic lady presented with sudden onset jerky movement of lower trunk and legs. It was present both in awake and sleep and got aggravated by mental stress as well as sensory stimulation. Examination revealed rhythmic jerks affecting muscles of lower abdomen and legs. The lower limbs had normal muscle bulk and power, increased tone, exaggerated deep tendon reflexes, bilateral flexor plantar response with normal sensory autonomic and cerebellar function. Investigations including CSF study, MRI of dorsal spine and NCV were normal. A combination therapy with tizanidine, baclofen and clonazepam induced gradual improvement within 6 weeks.

Fístulas arteriovenosas duromedulares: presentación de tres casos / Spinal dural arteriovenous fistulas: report of three cases

Las fístulas arteriovenosas duro-medulares (F.A.V.D.M.) representan el mayor grupo dentro de las malformaciones vasculares medulares, incluyendo éstas a un grupo diverso de lesiones adquiridas o congénitas con diferente hemodinamia y fisiopatología. En el caso de las F.A.V.D.M. la aferencia de ésta no participa en la irrigación medular, de modo que los síntomas están dados por la congestión venosa causada por la fístula. Presentamos 3 casos de pacientes que presentan lesión medular secundaria a F.A.V.D.M., tratados quirúrgicamente y sus resultados. Se efectúa una revisión de la anatomía y fisiología de estas lesiones.

Ressonância magnética na esclerose múltipla: análise de 270 casos / Magnetic resonance imaging in multiple sclerosis: analysis of 270 cases

O autor apresenta 270 casos de pacientes com história clínica e imagens de ressonância magnética compatíveis com esclerose múltipla. São feitas considerações sobre a incidência quanto ao sexo, grupos etários e localização das lesões. Por se tratar de doença considerada rara nos países tropicais, o autor tece considerações didáticas sobre os critérios clínicos e de imagem úteis na prática radiológica e alerta os neurologistas para o significado desta doença na capital (Curitiba) de um estado brasileiro (Paraná) situado entre os paralelos 22§ e 30§ Sul.

Dystonia : emerging concepts in pathophysiology.

The essential pathophysiological feature of dystonia is co-contraction of antagonistic muscles. This may be due to derangement of the spinal cord or cortical mechanism. In the cord, there is disruption of the normal reciprocal inhibition of antagonists during agonist contraction. This decreased reciprocal inhibition is due to reduced presynaptic inhibition of muscle afferent input to the inhibitory interneuron. The reduced presynaptic inhibition may in turn be either due to defective suprasegmental control or to changes in the tonic afferent input to the interneuron from cutaneous and muscle afferents. Alternatively, genesis of dystonia may entirely be a cortical mechanism. Overactivity of the premotor cortices, which receive projections from basal ganglia via ventral thalamus, could result in dystonia by abnormal activation of cortical motor neurons. This may again be due to a dopaminergic dysfunction of basal ganglia.

Enfermedad de Devic (Neuromielitis óptica) Hallazgos clínico-patológicos de diez casos de autopsia / (Devic disease (optic neuromyelitis). Clinical and pathologic features in 10 autopsy cases)

Se presentan los hallazgos clínico-pathológicos de diez casos de enfermedad de Devic. La enfermedad fue más frecuente en mujeres adultas y el tiempo de evolución promedio en esta serie fue de diez meses. Las manifestaciones por lesión de la médula espinal fueron las más sobresalientes y casi todos los enfermos murieron por complicaciones pulmonares. Los hallazgos neuropatológicos más importantes fueron desmielinización, infiltrado linfocitario perivascular y cavitación del quiasma óptico y de la médula espinal. Algunos autores consideran la enfermedad de Devic como una forma de esclerosis múltiple y otros como entidad aparte, pero se sabe que es una enfermedad desmielinizante primaria confinada a nervios, quiasma y bandeletas ópticos y a la médula espina, en que el grado de destrucción es mayor aún que en las placas más antiguas de la esclerosis múltiple

Clinical aspects of spinal cord meningiomas: analysis of forty cases

A retrospective analysis was performed on forty cases of spinal cord meningiomas, operated on at Dr. Shariati Hospital from 1976 to 1990. Age and sex distribution, clinical presentation and tumor location were comparable to those reported by others.'[15,12] In males the tumors were distributed evenly in cervical and dorsal areas and were often anterior to the cord. This finding makes a different surgical approach necessary. For prevention of postoperative CSF leakage and infection, repair and tight closure of the dura is mandatory. Concerning prognosis, even in paraplegic patients the chance of complete recovery is good

Post-traumatic chronic spinal cord injury: assessment with MRI

The initial experience concerning the use of magnetic resonance imaging in 94 patients who had sustained chronic cord injury showed its specific advantages over traditional imaging modalities. A variety of 84 cord abnormalities were identified including myelomalacia in 47%, cord cysts in 37%, focal atrophy in 11% and cord transection in 5%. Canal stenosis was seen in twenty-five patients, eleven of which were associated with herniated nucleus pulposus. The time interval post-injury varied from 5 months to 10 years which was independent of the type of injury. Myelopathy was usually observed at the site of initial injury. Although the majority of patients had cervical spine injuries [56%], the thoracic spinal cord appeared more susceptible to cyst development [40%]