Influences of Glabridin Treatment on Motor Function Recovery after Spinal Cord Injury / Influencia del Tratamiento con Glabridina en la Recuperación de la Función Motora después de una Lesión de la Médula Espinal

SUMMARY: Spinal cord injury (SCI) usually arises from compression due to traffic accidents and falls, resulting in varying degrees of movement, sensory loss, and possible paralysis. Glabridin (Gla) is a natural compound derived from licorice. It significantly affects drug development and medicine because of its anti-inflammatory, anti-oxidative, anti-tumoral, antibacterial, bone protective, cardiovascular protective, neuroprotective, liver protective, anti-obesity, and anti-diabetic properties. Various methods were employed to administer Gla to SCI mice in order to investigate its impact on the recovery of motor function. The mice were allocated into four cohorts using a randomization procedure. In the sham cohort, solely the lamina of vertebral arch was surgically exposed without causing any harm to the spinal cord tissue. Conversely, the injury cohort was subjected to spinal cord tissue damage and received no treatment thereafter. The mice in the remaining two cohorts received a dosage of 40 mg/kg Gla every two days via either intraperitoneal or intrathecal injection for a duration of 42 d following spinal cord injury. We conducted behavioral tests utilizing the Basso Mouse Scale score and gait analysis techniques. Magnetic resonance imaging and hematoxylin and eosin were employed to evaluate scar tissue formation. Systemic inflammation in mice was evaluated by employing an enzyme-linked immunosorbent assay. Gla promoted motor function recovery in mice following SCI and improved the pathological environment in the damaged area. These alterations were more evident in mice subjected to the intrathecal injection method. Intraperitoneal injections appear to be more beneficial for controlling systemic inflammatory responses. Although more intensive studies are required, Gla exhibits promising clinical potential as a cost-effective dietary phytochemical.

La lesión de la médula espinal (LME) generalmente surge de la compresión producto de caídas y accidentes de tránsito, lo que resulta en alteraciones del movimiento, pérdida sensorial y posible parálisis. La Glabridina (Gla) es un compuesto natural derivado del regaliz, constituyéndose en un aporte significativo para el desarrollo de fármacos y la medicina debido a sus propiedades antiinflamatorias, antioxidantes, antitumorales, antibacterianas, osteoprotectoras, cardioprotectoras, neuroprotectoras, hepatoprotectoras, antidiabéticas y contra la obesidad. En el presente trabajo se emplearon varios métodos para administrar Gla a ratones con lesión medular con el fin de investigar su impacto en la recuperación de la función motora. Los ratones fueron distribuidos en cuatro grupos mediante un procedimiento de aleatorización. En el grupo simulado, únicamente se expuso quirúrgicamente la lámina del arco vertebral sin causar ningún daño al tejido de la médula espinal. Por el contrario, el grupo lesionado fue sometido a daño del tejido de la médula espinal, sin recibir tratamiento posterior. Los ratones de los dos grupos restantes recibieron una dosis de 40 mg/kg de Gla cada dos días mediante inyección intraperitoneal o intratecal durante 42 días después de la lesión de la médula espinal. Fueron realizadas pruebas de comportamiento utilizando la puntuación de la escala Basso Mouse y técnicas de análisis de la marcha. Se emplearon imágenes por resonancia magnética y se aplicaron tinciones histológicas (Hematoxilina & Eosina) en muestras para evaluar la formación de tejido cicatricial. La inflamación sistémica en ratones se evaluó mediante el empleo de un ensayo inmunoabsorbente ligado a enzimas. Gla promovió la recuperación de la función motora en ratones después de una lesión medular y mejoró el entorno patológico en el área dañada. Estas alteraciones fueron más evidentes en ratones sometidos al método de inyección intratecal. Las inyecciones intraperitoneales parecen ser más beneficiosas para controlar las respuestas inflamatorias sistémicas. Aunque se requieren estudios más intensivos, Gla exhibe un potencial clínico prometedor como fitoquímico dietético rentable.

Neuro-protective effect of Linalool against spinal cord injury in rats and the mechanism involved / Efecto neuroprotector del Linalool contra la lesión de la médula espinal en ratas y el mecanismo involucrado

The current study was conducted to determine the neuroprotective role and mechanism of action of Linalool (LIN) in SCI. The SCI in Sprague-Dawley (SD) rats was induced by weight-drop contusion model. Results of the suggested that LIN showed improvement in the locomotor function of SCI rats in a BBB scoring analysis. It was found in agreement with histopathological analysis of spinal cord tissue where LIN improves the neuronal architecture of spinal cord tissues, and protect neurons from degeneration. It also reduces oxidative stress via modulating endogenous antioxidants (MDA, SOD, and GSH) and inhibits the generation of pro-inflammatory cytokines (TNF-α, IL-1ß, and IL-6). In western blot analysis, LIN showed dose-dependent reduction of expression of toll-like receptor (TLR-4) and nuclear factor-kappa B (NF-ĸB). Our study demonstrated that administration of Linalool alleviated spinal cord injury via anti-inflammatory and antioxidant activities in spinal cord tissues possibly due to inhibition of TLR4/NF-κB activation.

El estudio actual se realizó para determinar el papel neuroprotector y el mecanismo de acción de Linalool (LIN) en SCI. La LIN en ratas Sprague-Dawley (SD) se indujo mediante el modelo de contusión de caída de peso. Los resultados sugirieron que LIN mostró una mejora en la función locomotora de ratas SCI en un análisis de puntuación BBB. De acuerdo con el análisis histopatológico del tejido de la médula espinal se encontró que LIN mejora la arquitectura neuronal de los tejidos de la médula espinal y protege a las neuronas de la degeneración. También reduce el estrés oxidativo mediante la modulación de antioxidantes endógenos (MDA, SOD y GSH) e inhibe la generación de citocinas proinflamatorias (TNF-α, IL-1ß e IL-6). En el análisis de Western blot, LIN mostró una reducción dependiente de la dosis de la expresión del receptor tipo toll (TLR-4) y el factor nuclear kappa B (NF-ĸB). Nuestro estudio demostró que la administración de Linalool alivió la lesión de la médula espinal a través de actividades antiinflamatorias y antioxidantes en los tejidos de la médula espinal, posiblemente debido a la inhibición de la activación de TLR4/NF-κB.

Neuroprotective effect and mechanism of cPLA2 inhibitor increases autophagic flux on spinal cord injury / 中国骨伤

OBJECTIVE@#To investigate the mechanism of cytosolic phospholipase A2(cPLA2) inhibitor to improve neurological function after spinal cord injury (SCI).@*METHODS@#Thirty-six 3 months old female SD rats, with body mass (280±20) g, were divided into three groups (n=12):sham group, SCI group, and SCI+ arachidonyl trifluoromethyl ketone(AACOCF3) group. Balloon compression SCI model was established in all three groups. In the sham model group, the spinal cord compression model was created after the balloon was placed without pressure treatment, and the remaining two groups were pressurized with the balloon for 48 h. After successful modeling, rats in the SCI+AACOCF3 group were injected intraperitoneally with AACOCF3, a specific inhibitor of cPLA2. The remaining two groups of rats were injected intraperitoneally with saline. The animals were sacrificed in batches on 7 and 14 days after modeling, respectively. And the damaged spinal cord tissues were sampled for pathomorphological observation, to detect the expression of cPLA2 and various autophagic fluxPrelated molecules and test the recovery of motor function.@*RESULTS@#Spinal cord histomorphometry examination showed that the spinal cord tissue in the sham group was structurally intact, with normal numbers and morphology of neurons and glial cells. In the SCI group, spinal cord tissue fractures with large and prominent spinal cord cavities were seen. In the SCI+AACOCF3 group, the spinal cord tissue was more intact than in the SCI group, with more fused spinal cord cavities, more surviving neurons, and less glial cell hyperplasia. Western blot showed that the sham group had the lowest protein expression of LC3-Ⅱ, Beclin 1, p62, and cPLA2 compared with the SCI and SCI+AACOCF3 groups (P<0.05) and the highest protein expression of LC3-Ⅰ (P<0.05). P62 and cPLA2 expression in the SCI group were higher than in the SCI+AACOCF3 group (P<0.05). Behavioral observations showed that the time corresponding to BBB exercise scores was significantly lower in both the SCI and SCI+AACOCF3 groups than in the sham group (P<0.05). Scores at 3, 7, and 14 days after pressurization were higher in the SCI+AACOCF3 group than in the SCI group (P<0.05).@*CONCLUSION@#cPLA2 inhibitors can reduce neuronal damage secondary to SCI, promote neurological recovery and improve motor function by improving lysosomal membrane permeability and regulating autophagic flux.

Short-chain fatty acids ameliorate spinal cord injury recovery by regulating the balance of regulatory T cells and effector IL-17+ γδ T cells / 浙江大学学报（英文版）（B辑：生物医学和生物技术）

Spinal cord injury (SCI) causes motor, sensory, and autonomic dysfunctions. The gut microbiome has an important role in SCI, while short-chain fatty acids (SCFAs) are one of the main bioactive mediators of microbiota. In the present study, we explored the effects of oral administration of exogenous SCFAs on the recovery of locomotor function and tissue repair in SCI. Allen's method was utilized to establish an SCI model in Sprague-Dawley (SD) rats. The animals received water containing a mixture of 150 mmol/L SCFAs after SCI. After 21 d of treatment, the Basso, Beattie, and Bresnahan (BBB) score increased, the regularity index improved, and the base of support (BOS) value declined. Spinal cord tissue inflammatory infiltration was alleviated, the spinal cord necrosis cavity was reduced, and the numbers of motor neurons and Nissl bodies were elevated. Enzyme-linked immunosorbent assay (ELISA), real-time quantitative polymerase chain reaction (qPCR), and immunohistochemistry assay revealed that the expression of interleukin (IL)‍-10 increased and that of IL-17 decreased in the spinal cord. SCFAs promoted gut homeostasis, induced intestinal T cells to shift toward an anti-inflammatory phenotype, and promoted regulatory T (Treg) cells to secrete IL-10, affecting Treg cells and IL-17+ γδ T cells in the spinal cord. Furthermore, we observed that Treg cells migrated from the gut to the spinal cord region after SCI. The above findings confirm that SCFAs can regulate Treg cells in the gut and affect the balance of Treg and IL-17+ γδ T cells in the spinal cord, which inhibits the inflammatory response and promotes the motor function in SCI rats. Our findings suggest that there is a relationship among gut, spinal cord, and immune cells, and the "gut-spinal cord-immune" axis may be one of the mechanisms regulating neural repair after SCI.

Ferulic acid improves motor function induced by spinal cord injury in rats via inhibiting neuroinflammation and apoptosis

ABSTRACT Purpose To investigate the effect of ferulic acid (FA) on spinal cord injury (SCI)-induced motor dysfunction and to explore the possible pharmacological mechanisms. Methods Adult male Wistar rats were used in our study. SCI was achieved by clipping the spinal cord T9 of the rat by a vascular clip for 2 minutes. The motor function of the rat was evaluated by Basso, Beattie, and Bresnahan scoring method (BBB) and inclined plane test. Hematoxylin and eosin (HE) staining, NISSL staining, and transmission electron microscopic examination were used to evaluate alterations at the histological level. Polymerase chain reaction (PCR), Western blots, and enzyme-linked immunosorbent assays (ELISA) were employed in biochemical analysis. Results The BBB score and inclined plane test score significantly decreased after SCI surgery, whereas chronic FA treatment (dose of 90 mg/kg, i.g.) for 28 days improved SCI-induced motor dysfunction. HE staining showed that SCI surgery induced internal spinal cord edema, but the structural changes of the spinal cord could be reversed by FA treatment. NISSL staining and transmission electron microscopic examination confirmed the improvement of the effect of FA on the injury site. In the biochemical analysis, it could be found that FA inhibitedSCI-induced mRNA and protein overexpression of pro-inflammatory cytokines (IL-1β, IL-6, TNF-α), as well as iNOS and COX-2 via the modulation of NF-κB level in the spinal cord of SCI rat. Moreover, the SCI-induced decrease of Bcl-2/Bax ratio was also reversed by FA treatment. However, the effect of FA on the expression of Beclin-1 was not statistically significant. Conclusions FA showed a therapeutic effect on SCI, which may be associated with the regulation of neuroinflammation and apoptosis.

Evaluation of the effects of erythropoietin and interleukin-6 in rats submitted to acute spinal cord injury

OBJECTIVE: To evaluate the effects of interleukin-6 (IL-6) and erythropoietin (EPO) in experimental acute spinal cord injury (SCI) in rats. METHODS: Using standardized equipment, namely, a New York University (NYU) Impactor, a SCI was produced in 50 Wistar rats using a 10-g weight drop from a 12.5-mm height. The rats were divided into the following 5 groups of 10 animals each: "Group EPO", treated with erythropoietin only; "Group EPO + IL-6", treated with both substances; "Group IL-6", receiving IL-6 administration only; "Group Placebo", receiving a placebo solution; and "Group Sham", submitted to an incomplete procedure (only laminectomy, without SCI). All drugs and the placebo solution were administered intraperitoneally for three weeks. The animals were followed up for 42 days. Functional motor recovery was monitored by the Basso, Beattie, and Bresnahan (BBB) scale on days 2, 7, 14, 21, 28, 35 and 42. Motor-evoked potential tests were performed on the 42nd day. Histological analysis was performed after euthanasia. RESULTS: The group receiving EPO exhibited superior functional motor results on the BBB scale. IL-6 administration alone was not superior to the placebo treatment, and the IL-6 combination with EPO yielded worse results than did EPO alone. CONCLUSIONS: Using EPO after acute SCI in rats yielded benefits in functional recovery. The combination of EPO and IL-6 showed benefits, but with inferior results compared to those of isolated EPO; moreover, isolated use of IL-6 resulted in no benefit.

Influence of tramadol on functional recovery of acute spinal cord injury in rats

Abstract Purpose: To evaluate the influence tramadol on functional recovery of acute spinal cord injury in rats. Methods: Ten rats were divided into two groups (n = 5). All animals were submitted by a laminectomy and spinal cord injury at eighth thoracic vertebra. In control group, the rats didn't receive any analgesic. In tramadol group, the rats received tramadol 4mg/Kg at 12/12h until 5 days by subcutaneous. Animals were following by fourteen days. Was evaluated the Basso, Beattie, Bresnahan scale (locomotor evaluation) and Rat Grimace Scale (pain evaluation) at four periods. Results: There no difference between the groups in locomotor evaluation in all periods evaluated (p>0.05) and in both groups there was a partial recover of function. The tramadol group show a lower pain levels at the first, third and seventh postoperatively days when comparing to the control group. Conclusion: The tramadol as an analgesic agent don't influence on functional recovery of acute spinal cord injury in rats

Protective effects of melatonin on spinal cord injury / Efectos protectores de la melatonina en lesión de la médula espinal

Spinal cord injury causes neuron nerve fiber loss. The aim of this study was to investigate the neuroprotective, inflammatory and angiogenetic effects of melatonin on rat spinal cord injury (SCI). For spinal cord injury, a standard weight reduction method was used that caused moderate severity of injury (100 g / cm force) at T10 Melatonin (10 mg/kg intraperitoneally ) was administered for 10 days after trauma. Each group consisted of 10 animals. of these, six were used for biochemical and four were used for the evaluation of histological analysis. Spinal cord samples were taken for histological examination or determination of malondialdehyde (MDA) and glutathione (GSH) levels, myeloperoxidase (MPO) activity. Spinal cord injury and melatonin treated group were compared. Melatonin administration in spinal cord injury increased the activity of glial cells in the radial and funicular cells and ependymal cells and increased the activity of glial cells and also showed a positive effect on inflammation and vascular endothelial cells in synaptic connections in the nerve fibers undergoing spinal injury endothelial degeneration It is thought that it can regulate the degenerative effect which is caused by both the inflammatory effect and the angiogenic effect which will have a positive effect on the neural connection.

La lesión de la médula espinal (SCI) provoca daño en la fibra nerviosa, que puede conducir a alteraciones motoras y sensitivas, incluso la muerte. El objetivo de este estudio fue investigar los efectos neuroprotectores, proinflamatorios y proangiogénicos de la melatonina en un modelo de SCI inducida en rata. Para tal efecto se utilizaron dos grupos: Grupo 1 (n:10) se le indujo una SCI, mediante el método de reducción de peso estándar (100 g/cm fuerza), provocando una lesión de severidad moderada. Grupo 2 (n:10) inducción SCI más aplicación de T10 Melatonina (10 mg / kg v.i.) durante 10 días después del trauma. Muestras de seis animales de cada grupo fueron usados para análisis bioquímicos y los otros cuatro para la evaluación histológica. Se tomaron muestras de médula espinal para el examen histológico y para la determinación de niveles de malondialdehído (MDA) y glutatión (GSH), actividad mieloperoxidasa (MPO) y se comparó la lesión de la médula espinal y el grupo tratado con melatonina. La administración de melatonina en la lesión de la médula espinal aumentó la actividad de las células gliales en las células radiales, funiculares y ependimocitos. Ademas mostró un efecto positivo sobre la inflamación y angiogénesis en las conexiones sinápticas en las fibras nerviosas sometidas a lesión espinal. Pudiendo este participar en la regulación del efecto degenerativo causado, principalmente, por acción de angiogénesis e inflamación local.

Neuroprotective effects of Ganoderma lucidum on spinal cord injury / Efectos neuroprotectores de Ganoderma lucidum en la lesión de la médula espinal 1

SUMMARY: Traumatic injury to the spinal cord results in the delayed dysfunction and neuronal death. Impaired mitochondrial function, generation of reactive oxygen species (ROS), and lipid peroxidation occur soon after traumatic spinal cord injury (SCI), while the activation of compensatory molecules that neutralize ROS occurs at later time points. The aim of the current study was to investigate the putative neuroprotective effect of Ganoderma lucidum in a rat model of SCI. In order to induce SCI, a standard weight-drop method that induced a moderately severe injury (100 g/cm force) at T10, was used. Injured animals were given either 20 mL/kg Ganoderma lucidum or saline 30 min post injury per day by gastric gavage. At seven days postinjury, rats were decapitated. Spinal cord samples were taken for histological examination or determination of malondialdehyde (MDA) and glutathione (GSH) levels, myeloperoxidase (MPO) activity. SCI caused a significant decrease in spinal cord GSH content, which was accompanied with significant increases in MDA levels, MPO activity. On the other hand, Ganoderma lucidum treatment reversed all these biochemical parameters as well as SCI-induced histopathological alterations. Furthermore, impairment of the neurological functions due to SCI was improved by meloxicam treatment. The present study suggests that Ganoderma Lucidum, reduces SCI-induced oxidative stress and exerts neuroprotection by inhibiting lipid peroxidation, GSH depletion.

RESUMEN: La lesión traumática de la médula espinal provoca disfunción retrasada y muerte neuronal. La función mitocondrial deteriorada, la generación de especies reactivas de oxígeno (ERO) y la peroxidación lipídica ocurren poco después de una lesión traumática de la médula espinal (LTE), mientras que la activación de moléculas compensatorias que neutralizan ERO ocurre posteriormente. El objetivo del presente estudio fue investigar el efecto neuroprotector de Ganoderma lucidum en un modelo de LTE en ratas. Con el fin de inducir LTE, se utilizó un método estándar de pérdida de peso que indujo una lesión moderadamente grave (100 g / cm de fuerza) a T10. A los animales lesionados se les administró 20 ml / kg de Ganoderma lucidum o solución salina, por sonda gástrica, 30 minutos después de la lesión. A los siete días después de la lesión, las ratas fueron eutanasiadas por decapitación. Se tomaron muestras de médula espinal para el examen histológico y para la determinación de los niveles de malondialdehído (MDA) y glutatión (GSH), y la actividad de mieloperoxidasa (MPO). LTE causó una disminución significativa en el contenido de GSH de la médula espinal, además de aumentos significativos en los niveles de MDA y la actividad de MPO. Por otro lado, el tratamiento con Ganoderma lucidum invirtió todos estos parámetros bioquímicos así como las alteraciones histopatológicas inducidas por LTE. El deterioro de las funciones neurológicas debidas a LTE mejoró con el tratamiento con meloxicam. El presente estudio sugiere que Ganoderma lucidum, reduce el estrés oxidativo inducido por LTE y ejerce la neuroprotección mediante la inhibición de la peroxidación de los lípidos y agotamiento del GSH.

Effects of aquaporin 4 and inward rectifier potassium channel 4 1 on medullospinal edema after methylprednisolone treatment to suppress acute spinal cord injury in rat

Abstract Purpose: To investigate the effects of aquaporin 4 (AQP4) and inward rectifier potassium channel 4.1 (Kir4.1) on medullospinal edema after treatment with methylprednisolone (MP) to suppress acute spinal cord injury (ASCI) in rats. Methods: Sprague Dawley rats were randomly divided into control, sham, ASCI, and MP-treated ASCI groups. After the induction of ASCI, we injected 30 mg/kg MP via the tail vein at various time points. The Tarlov scoring method was applied to evaluate neurological symptoms, and the wet-dry weights method was applied to measure the water content of the spinal cord. Results: The motor function score of the ASCI group was significantly lower than that of the sham group, and the spinal water content was significantly increased. In addition, the levels of AQP4 and Kir4.1 were significantly increased, as was their degree of coexpression. Compared with that in the ASCI group, the motor function score and the water content were significantly increased in the MP group; in addition, the expression and coexpression of AQP4 and Kir4.1 were significantly reduced. Conclusion: Methylprednisolone inhibited medullospinal edema in rats with acute spinal cord injury, possibly by reducing the coexpression of aquaporin 4 and Kir4.1 in medullospinal tissues.

Granulocyte colony-stimulating factor combined with Methylprednisolone improves functional outcomes in rats with experimental acute spinal cord injury

OBJECTIVES: To evaluate the effects of combined treatment with granulocyte colony-stimulating factor (G-CSF) and methylprednisolone in rats subjected to experimental spinal cord injury. METHODS: Forty Wistar rats received a moderate spinal cord injury and were divided into four groups: control (no treatment); G-CSF (G-CSF at the time of injury and daily over the next five days); methylprednisolone (methylprednisolone for 24 h); and G-CSF/Methylprednisolone (methylprednisolone for 24 h and G-CSF at the time of injury and daily over the next five days). Functional evaluation was performed using the Basso, Beattie and Bresnahan score on days 2, 7, 14, 21, 28, 35 and 42 following injury. Motor-evoked potentials were evaluated. Histological examination of the spinal cord lesion was performed immediately after euthanasia on day 42. RESULTS: Eight animals were excluded (2 from each group) due to infection, a normal Basso, Beattie and Bresnahan score at their first evaluation, or autophagy, and 32 were evaluated. The combination of methylprednisolone and G-CSF promoted greater functional improvement than methylprednisolone or G-CSF alone (p<0.001). This combination also exhibited a synergistic effect, with improvements in hyperemia and cellular infiltration at the injury site (p<0.001). The groups displayed no neurophysiological differences (latency p=0.85; amplitude p=0.75). CONCLUSION: Methylprednisolone plus G-CSF promotes functional and histological improvements superior to those achieved by either of these drugs alone when treating spinal cord contusion injuries in rats. Combining the two drugs did have a synergistic effect.

Systematic review of recovery of spinal cord injury with antioxidant therapy / Revisão sistemática da recuperação de trauma raquimedular com terapia antioxidante / Revisión sistemática de recuperación de trauma raquimedular con terapia antioxidante

ABSTRACT The objective of the paper is to analyze the frequency and efficacy of experimental studies with antioxidant therapy. A search was conducted in the pubmed.gov database using the keywords "antioxidants" AND "spinal cord injury", from January 2000 to December 2015, resulting in 686 articles. Studies of non-traumatic injuries, non-antioxidant therapies, absence of neurological and functional evaluation, and non-experimental studies were excluded, leaving a total of 43 articles. The most used therapies were melatonin (16.2%), quercetin (9.3%), epigallocatechin and edaravone (6.9%). The most frequent route of administration was intraperitoneal (72.09%). The dose and mode of administration varied greatly, with a single dose being the most commonly used (39.53%). The time elapsed from trauma to treatment was 0-15 minutes (41.8%), 15-60 minutes (30%) and over 60 minutes (10.6%). Histological analysis was performed in 32 studies (74.41%). The BBB scale was the main functional measure applied (55.8%), followed by the inclined plane test (16.2%) and the Tarlov scale (13.9%). Positive outcomes were observed in 37 studies (86.04%). The heterogeneity of antioxidant therapy, with different types, doses, and measurements observed, limits the comparison of efficacy. Standardized protocols are required to make clinical translation possible.

RESUMO O objetivo do presente estudo é analisar a frequência e a eficácia dos estudos experimentais com terapia antioxidante. Realizou-se uma pesquisa na base de dados pubmed.gov usando as palavras-chave "antioxidants" (antioxidantes) AND "spinal cord injury" (trauma raquimedular), de janeiro de 2000 a dezembro de 2015, resultando em 686 artigos. Estudos de lesões não traumáticas, terapias não antioxidantes, ausência de avaliação neurológica e funcional e estudos não experimentais foram excluídos, restando 43 artigos. As terapias mais utilizadas foram melatonina (16,2%), quercetina (9,3%), epigalocatequina e edaravona (6,9%). A via de administração mais frequente foi intraperitoneal (72,09%). A posologia e o modo de administração tiveram grande variação, sendo que a dose única foi a forma mais frequente (39,53%). O tempo decorrido desde o trauma até a instituição do tratamento foi de 0 a 15 minutos (41,8%), 15 a 60 minutos (30%) e acima de 60 minutos (10,6%). A análise histológica foi realizada em 32 estudos (74,41%). O sistema de escala BBB foi a principal medida funcional aplicada (55,8%), seguida de teste com plano inclinado (16,2%) e a escala de Tarlov (13,9%). Os desfechos positivos foram observados em 37 estudos (86,04%). A heterogeneidade da terapia antioxidante com diferentes tipos, doses e medições observadas limita a comparação da eficácia. Protocolos padronizados são necessários para tornar possível a tradução clínica.

RESUMEN El objetivo del presente estudio es analizar la frecuencia y eficacia de los estudios experimentales con terapia antioxidante. Se realizó una búsqueda en la base de datos pubmed.gov utilizando las palabras clave "antioxidants" (antioxidantes) AND "spinal cord injury" (trauma raquimedular), de enero de 2000 a diciembre de 2015, y se encontraron 686 artículos. Se excluyeron los estudios de lesiones no traumáticas, terapias no antioxidantes, con ausencia de evaluación neurológica y funcional y los estudios no experimentales, quedando 43 artículos. Las terapias más utilizadas fueron melatonina (16,2%), quercetina (9,3%), epigalocatequina y edaravona (6,9%). La vía de administración más común fue intraperitoneal (72,09%). La dosificación y administración fueron variadas, pero la dosis única fue la forma más frecuente (39,53%). El tiempo trascurrido desde el trauma a la iniciación del tratamiento fue de 0-15 minutos (41,8%), 15 a 60 minutos (30%) y más de 60 minutos (10,6%). El análisis histológico se realizó en 32 estudios (74,41%). El sistema de la escala BBB se aplicó como la principal medición funcional (55,8%), seguida por la prueba del plano inclinado (16,2%) y la escala de Tarlov (13,9%). Se observaron resultados positivos en 37 estudios (86,04%). La heterogeneidad de la terapia antioxidante con diferentes tipos, dosis y mediciones observados limita la comparación de la eficacia. Son necesarios protocolos estandarizados para tornar posible la traducción clínica.

Effects of ganglioside G(M1) and erythropoietin on spinal cord lesions in rats: functional and histological evaluations

OBJECTIVE: To evaluate the functional and histological effects of ganglioside G(M1) and erythropoietin after experimental spinal cord contusion injury. METHODS: Fifty male Wistar rats underwent experimental spinal cord lesioning using an NYU-Impactor device and were randomly divided into the following groups, which received treatment intraperitoneally. The G(M1) group received ganglioside G(M1) (30 mg/kg); the erythropoietin group received erythropoietin (1000 IU/kg); the combined group received both drugs; and the saline group received saline (0.9%) as a control. A fifth group was the laminectomy group, in which the animals were subjected to laminectomy alone, without spinal lesioning or treatment. The animals were evaluated according to the Basso, Beattie and Bresnahan (BBB) scale, motor evoked potential recordings and, after euthanasia, histological analysis of spinal cord tissue. RESULTS: The erythropoietin group had higher BBB scores than the G(M1) group. The combined group had the highest BBB scores, and the saline group had the lowest BBB scores. No significant difference in latency was observed between the three groups that underwent spinal cord lesioning and intervention. However, the combined group showed a significantly higher signal amplitude than the other treatment groups or the saline group (p<0.01). Histological tissue analysis showed no significant difference between the groups. Axonal index was significantly enhanced in the combined group than any other intervention (p<0.01). CONCLUSION: G(M1) and erythropoietin exert therapeutic effects on axonal regeneration and electrophysiological and motor functions in rats subjected to experimental spinal cord lesioning and administering these two substances in combination potentiates their effects.

Effects of estrogen on functional and neurological recovery after spinal cord injury: An experimental study with rats

OBJECTIVES:To evaluate the functional and histological effects of estrogen as a neuroprotective agent after a standard experimentally induced spinal cord lesion.METHODS:In this experimental study, 20 male Wistar rats were divided into two groups: one group with rats undergoing spinal cord injury (SCI) at T10 and receiving estrogen therapy with 17-beta estradiol (4mg/kg) immediately following the injury and after the placement of skin sutures and a control group with rats only subjected to SCI. A moderate standard experimentally induced SCI was produced using a computerized device that dropped a weight on the rat's spine from a height of 12.5 mm. Functional recovery was verified with the Basso, Beattie and Bresnahan scale on the 2nd, 7th, 14th, 21st, 28th, 35th and 42nd days after injury and by quantifying the motor-evoked potential on the 42nd day after injury. Histopathological evaluation of the SCI area was performed after euthanasia on the 42nd day.RESULTS:The experimental group showed a significantly greater functional improvement from the 28th to the 42nd day of observation compared to the control group. The experimental group showed statistically significant improvements in the motor-evoked potential compared with the control group. The results of pathological histomorphometry evaluations showed a better neurological recovery in the experimental group, with respect to the proportion and diameter of the quantified nerve fibers.CONCLUSIONS:Estrogen administration provided benefits in neurological and functional motor recovery in rats with SCI beginning at the 28th day after injury.

Side effects of steroid use in patients with traumatic spinal cord injury / Efeitos colaterais do uso de esteroides em pacientes com lesão medular traumática / Efectos secundarios del uso de esteroides en pacientes con lésion medular traumática

OBJECTIVE: Indicate and identify potential complications in our unit associated with the use of steroids in patients over 16 years of age with traumatic acute spinal cord injury managed with NASCIS II, III scheme compared with patients with the same characteristics who did not receive this management. METHODS: To conduct a research study with reports of cases and controls in patients over 16 years of age and with an established diagnosis of acute spinal cord injury, treated definitively in our unit, performing the comparison of evolutionary process between those treated with steroids and those who were not, based on the development of a data collection sheet with several variables.. The results were encoded, tabulated and analyzed. RESULTS: A total of 30 patients were analyzed from January to December 2012 and it was found that 16% of the patients managed with the steroid scheme required admission to the intensive care unit, 40% developed hospital-acquired pneumonia, 17% had urinary tract infection, 3% progressed to respiratory failure and 20% of this group had gastrointestinal bleeding. CONCLUSIONS: It was concluded that steroid management is not a risk-free therapy and the recommendation is to make a direct assessment of the potential benefit to its use in relation to the possible complications that can ensue before choosing this option in patients with traumatic spinal cord injury. .

OBJETIVO: Sinalizar e identificar possíveis complicações em nossa unidade, associadas ao uso de esteroides em pacientes com mais de 16 anos de idade com lesão medular aguda manejados com esquema NASCIS II, III em comparação com pacientes com as mesmas características que não receberam esse tratamento. MÉTODOS: Realizar um estudo de investigação com relato de casos e controles em pacientes com mais de 16 anos de idade e com diagnóstico estabelecido de lesão medular traumática aguda, tratados de maneira definitiva em nossa unidade, realizando a comparação do processo evolutivo intra-hospitalar entre os que foram tratados com esteroides e os que não foram, com base na elaboração de uma folha de captura com diversas variáveis. Os resultados foram codificados, tabulados e analisados. RESULTADOS: Um total de 30 pacientes foi analisado no período de janeiro a dezembro de 2012, verificando que dos pacientes tratados com o esquema de esteroides, 16% precisaram de internação em terapia intensiva, 40% desenvolveram pneumonia hospitalar, 17% apresentaram infecção do trato urinário, 3% evoluíram para insuficiência respiratória e 20% deste grupo apresentaram sangramento gastrintestinal. CONCLUSÕES: Conclui-se que o manejo com esteroides não é uma terapia livre de riscos e se recomenda realizar uma avaliação direta do possível benefício do uso dessa medicação com relação às possíveis complicações que podem sobrevir antes de escolher essa opção em pacientes com lesão medular traumática. .

OBJETIVO: Señalar y determinar las posibles complicaciones en nuestra unidad asociadas al uso de esteroides en pacientes mayores de 16 años de edad con lesión medular aguda manejados con esquema NASCIS II, III en comparación con pacientes bajo las mismas características que no recibieron este manejo. MÉTODOS: Realizar un estudio de investigación con reporte de casos y controles en pacientes con diagnostico establecido de lesión medular aguda traumática en mayores de 16 años tratados de manera definitiva en nuestra unidad, realizando una comparativa en el proceso evolutivo intrahospitalario entre aquellos que fueron manejados con esteroides y aquellos que no lo fueron en base a la elaboración de una hoja de captura con diversas variables. Los resultados fueron codificados, tabulados y analizados. RESULTADOS: Se analizó un total de 30 pacientes en el periodo de Enero a Diciembre de 2012 encontrando que aquellos pacientes manejados con esquema de esteroides, un 16% requirieron atención en terapia intensiva, 40% desarrollaron neumonía intrahospitalaria, 17% presentaron infección de vías urinarias, un 3% cursó con falla respiratoria y 20% de este grupo presentaron sangrado de tubo digestivo. CONCLUSIONES: Se concluye que el manejo con esteroides no es una terapia libre de riesgo y se hace la recomendación de realizar una evaluación directa del posible beneficio que puede otorgar este manejo contra las potenciales complicaciones a desarrollar antes de elegir esta opción en pacientes con lesión medular traumática. .

Inflammation & apoptosis in spinal cord injury.

Spinal cord injury (SCI) consists of a two-steps process involving a primary mechanical injury followed by an inflammatory process and apoptosis. Secondary insult is characterized by further destruction of neuronal and glial cells, and leads to expansion of the damage, so that the paralysis can extend to higher segments. With the identification of mechanisms that either promote or prevent neuronal inflammation and apoptosis come new approaches for preventing and treating neurodegenerative disorders. From a clinical perspective, this article discusses novel targets for the development of therapeutic agents that have the potential to protect the spinal cord from irreversible damage and promote functional recovery.

effects of cyclosporin-A on functional outcome and axonal regrowth following spinal cord injury in adult rats

It has been shown that the immunophilin ligands have the special advantage in spinal cord repair. In this study, the effects of cyclosporine A [CsA] on functional recovery and histological outcome were evaluated following spinal cord injury in rats. After spinal cord hemisection in thirty six adult female Sprague-Dawley rats [200- 250 g], treatment groups received CsA [2.5 mg/kg i.p.] at 15min and 24h after lesion [CsA 15min group and CsA 24h group] daily, for 8 weeks. Control and sham groups received normal saline and in sham operated animals the spinal cord was exposed in the same manner as treatment groups, but was not hemisected. Hindlimb motor function was assessed in 1, 3, 5 and 7 weeks after lesion, using locomotive rating scale developed by Basso, Bresnahan and Beattie [BBB]. Motor neurons were counted within the lamina IX of ventral horn and lesion size was measured in 5 mm of spinal lumbar segment with the epicenter of the lesion site. The mean number of motor neurons and the mean BBB scale in 3, 5 and 7 weeks in CsA 15min groups significantly increased compared to the control group. Although, the lesion size reduced in rats with CsA treatment compared to the control group, no significant difference was observed. Thus, it can be concluded that CsA can improve locomotor function and histological outcome in the partial spinal cord injury

Effects of valproic acid, a histone deacetylase inhibitor, on improvement of locomotor function in rat spinal cord injury based on epigenetic science

The primary phase of traumatic spinal cord injury [SCI] starts by a complex local inflammatory reaction such as secretion of pro-inflammatory cytokines from microglia and injured cells that substantially contribute to exacerbating pathogenic events in secondary phase. Valproic acid [VPA] is a histone deacetylase inhibitor. Acetylation of histones is critical to cellular inflammatory and repair processes. In this study, rats were randomly assigned to five experimental groups [laminectomy, untreated, and three VPA-treated groups]. For SCI, severe contusion was used. In treated groups, VPA was administered intraperitoneally at doses of 100, 200 and 400 mg/kg daily three hours after injury for 7 days. To compare locomotor improvement among experimental groups, behavioral assessments were performed by the Basso, Beattie and Bresnahan [BBB] rating scale. The expression of neurotrophins was evaluated by RT-PCR and real-time PCR. VPA administration increased regional brain-derived neurotrophic factor and glial cell-derived neurotrophic factor mRNA levels. Local inflammation and the expression of the lysosomal marker ED1 by activated macrophages/microglial cells were reduced by VPA and immunoreactivity of acetylated histone and microtubule-associated protein were increased. The results showed a reduction in the development of secondary damage in rat spinal cord trauma with an improvement in the open field test [BBB scale] with rapid recovery

Pregabalin as a Neuroprotector after Spinal Cord Injury in Rats: Biochemical Analysis and Effect on Glial Cells

As one of trials on neuroprotection after spinal cord injury, we used pregabalin. After spinal cord injury (SCI) in rats using contusion model, we observed the effect of pregabalin compared to that of the control and the methylprednisolone treated rats. We observed locomotor improvement of paralyzed hindlimb and body weight changes for clinical evaluation and caspase-3, bcl-2, and p38 MAPK expressions using western blotting. On histopathological analysis, we also evaluated reactive proliferation of glial cells. We were able to observe pregabalin's effectiveness as a neuroprotector after SCI in terms of the clinical indicators and the laboratory findings. The caspase-3 and phosphorylated p38 MAPK expressions of the pregabalin group were lower than those of the control group (statistically significant with caspase-3). Bcl-2 showed no significant difference between the control group and the treated groups. On the histopathological analysis, pregabalin treatment demonstrated less proliferation of the microglia and astrocytes. With this animal study, we were able to demonstrate reproducible results of pregabalin's neuroprotection effect. Diminished production of caspase-3 and phosphorylated p38 MAPK and as well as decreased proliferation of astrocytes were seen with the administration of pregabalin. This influence on spinal cord injury might be a possible approach for achieving neuroprotection following central nervous system trauma including spinal cord injury.

Estudo radiológico do valor angular da cifose torácica em adolescentes / Estudio radiológico del valor angular de la cifosis torácica en adolescentes / Radiological study of the angular value of thoracic kyphosis in adolescents

OBJETIVO: determinar a diferença dos valores angulares da cifose torácica utilizando como vértebra terminal cranial diferentes níveis (T2 a T5). MÉTODOS: foram avaliadas radiografias em perfil de cem adolescentes voluntários saudáveis da Escola Industrial do Serviço Social da Indústria (SESI) de Ribeirão Preto (SP), com prévia autorização dos pais ou responsáveis. Foram excluídas as radiografias de dez indivíduos por falhas na qualidade. Os parâmetros avaliados foram: mensuração da cifose torácica pelo método de Cobb, utilizando T2, T3, T4 ou T5 como vértebra terminal cranial e T12 como vértebra terminal caudal. RESULTADOS: foram avaliados 90 indivíduos (46 do sexo masculino e 44 do feminino), com idade variando de 13 a 15 anos (média 14±6). O valor angular da cifose torácica nos diferentes níveis variou entre 45º (T2-T12) e 35º (T5-T12) no sexo masculino, e valor angular entre 43º(T2-T12) e 30º (T5-T12) no sexo feminino. CONCLUSÃO: foi observada diferença constante de aproximadamente 5º quando comparados os valores angulares da cifose torácica utilizando diferentes níveis (T2 a T5) como vértebra terminal cranial.

OBJECTIVE: to determine the difference of the thoracic kyphosis angular values using different levels (T2 a T5) as a terminal cranial vertebra. METHODS: sagittal radiographies of one hundred healthy adolescent volunteers, who study at Escola Industrial do Serviço Social da Indústria (SESI) in Ribeirão Preto SP), were evaluated the sagittal radiographies of one hundred health volunteers adolescent, that studies at Escola Industrial do SESI in Ribeirão Preto (SP), with parents consent. Ten adolescents were excluded because of flaws in the quality. The studied parameters were: the measurement of thoracic kyphosis by the Cobb method, using T2, T3, T4, T5 as a terminal proximal vertebra and T12 as a distal final vertebra. RESULTS: Ninety individuals (46 men and 44 women), aged from 13 to 15 (average of 14±6), were evaluated. The angular value of thoracic kyphosis in the different levels varied from 46º (T2 - T12) to 35º (T5 - T12) in men, and from 44º (T2- T12) to 30º (T5 - T12) in women. CONCLUSION: A constant difference of approximately 5º was observed when comparing the angular values of thoracic kyphosis using different levels (T2 - T5) as a terminal cranial vertebra.

OBJETIVO: determinar la diferencia de los valores angulares de la cifosis torácica usando como vértebra terminal craneal, diferentes niveles (T2 a T5). MÉTODOS: fueron evaluadas radiografías en perfil de cien adolescentes voluntarios saludables de la Escola Industrial do Serviço Social da Indústria (SESI) de Ribeirão Preto (SP), con previa autorización de sus padres o responsables. Fueron excluidas radiografías de diez individuos por fallas de resolución. Los parámetros evaluados fueron: la medida de la cifosis torácica por el método de Cobb, usando T2,T3,T4 y T5 como vértebra terminal craneal y T12 como vértebra terminal caudal. RESULTADOS: fueron evaluados 90 individuos (46 hombres y 44 mujeres), con edades que varían de 13 a 15 años (media 14±6). El valor angular de la cifosis torácica en los diferentes niveles fue de 45º (T2-T12) y 35º (T5-T12) en el sexo masculino, y valor angular de 43º (T2-T12) y 30º (T5-T12) en el sexo femenino. CONCLUSIÓN: fue observada una diferencia constante de aproximadamente 5º cuando los valores angulares de la cifosis torácica fueron comparados, usando diferentes niveles (T2 a T5) como vértebra terminal craneal.