The efficacy of immediate implantation of macroporous poly(N-[2-hydroxypropyl]-methacrylamide) hydrogel after laceration spinal cord injury in young rats / Eficacia de la implantación inmediata de hidrogel macroporoso de poli (N- [2-hidroxipropil] - metacrilamida) después de una lesión de la médula espinal en ratas jóvenes

SUMMARY: Spinal cord regeneration after mechanical injury is one of the most difficult biomedical problems. This article evaluates the effect of poly(N-[2-hydroxypropyl]-methacrylamide) hydrogel (PHPMA-hydrogel) on spinal cord regeneration in young rats after lateral spinal cord hemi-excision (laceration) at the level of segments T12-T13 (TrGel group). The locomotor function score (FS) and the paretic hindlimb spasticity score (SS) were assessed according to Basso-Beattie-Bresnahan (BBB) and Ashworth scales, respectively, and compared to a group of animals with no matrix implanted (Tr group). Regeneration of nerve fibers at the level of injury was evaluated at ~5 months after spinal cord injury (SCI). One week after the SCI induction, the FS on the BBB scale was 0.9±0.5 points in the Tr group and 3.6±1.2 points in the TrGel group. In the Tr group, the FS in 5 months was significantly lower than in 2 weeks after SCI, while no significant changes in FS were detected in the TrGel group over the entire observation period. The final FS was 0.8±0.3 points in the Tr group and 4.5±1.8 points in the TrGel group. No significant changes in SS have been observed in the TrGel group throughout the experiment, while the Tr group showed significant increases in SS at 2nd week, 6th week, 3th month and 5th month. The SS in 5 months was 3.6±0.3 points on the Ashworth scale in the Tr group and 1.8±0.7 points in the TrGel group. Throughout the observation period, significant differences in FS between groups were observed only in 5 weeks after SCI, whereas significant differences in SS were observed in 2, 3 and 6-8 weeks post-injury. Glial fibrous tissue containing newly formed nerve fibers, isolated or grouped in small clusters, that originated from the surrounding spinal cord matter have been found between the implanted hydrogel fragments. In conclusion, PHPMA-hydrogel improves recovery of the hindlimb locomotor function and promotes regenerative growth of nerve fibers. Further research is needed to clarify the mechanism of this PHPMA-hydrogel effect.

RESUMEN: La regeneración de la médula espinal después de una lesión mecánica es uno de los problemas biomédicos más difíciles. Este artículo evalúa el efecto del hidrogel de poli (N- [2-hidroxipropil] -metacrilamida) (PHPMA-hidrogel) sobre la regeneración de la médula espinal en ratas jóvenes después de la hemiescisión lateral de la médula espinal (lesión) a nivel de los segmentos T12 - T13 (Grupo TrGel). La puntuación de la función locomotora (FS) y la puntuación de espasticidad parética de las patas traseras (SS) se evaluaron de acuerdo con las escalas de Basso- Beattie-Bresnahan (BBB) y Ashworth, respectivamente, y se compararon con un grupo de animales sin matriz implantada (grupo Tr). Se evaluó la regeneración de las fibras nerviosas al nivel de la lesión ~ 5 meses después de la lesión de la médula espinal (LME). Una semana después de la inducción de SCI, el FS en la escala BBB fue 0,9 ± 0,5 puntos en el grupo Tr y 3,6 ± 1,2 puntos en el grupo TrGel. En el grupo Tr, el FS en 5 meses fue significativamente menor que en 2 semanas después de SCI, mientras que no se detectaron cambios significativos en FS en el grupo TrGel durante el período de observación. El FS final fue de 0,8 ± 0,3 puntos en el grupo Tr y de 4,5 ± 1,8 puntos en el grupo TrGel. No se han obser- vado cambios significativos en SS en el grupo TrGel durante el experimento, mientras que el grupo Tr mostró aumentos significativos en SS en la 2ª semana, 6ª semana, 3º mes y 5º mes. La SS en 5 meses fue de 3,6 ± 0,3 puntos en la escala de Ashworth en el grupo Tr y de 1,8 ± 0,7 puntos en el grupo TrGel. A lo largo del período de observación, se observaron diferencias significativas en FS entre los grupos solo en 5 semanas después de la LME, mientras que se observaron diferencias significativas en SS en 2, 3 y 6-8 semanas después de la lesión. Entre los fragmentos de hidrogel implantados se observó tejido fibroso glial que contenía fibras nerviosas recién formadas, aisladas o agrupadas en pequeños grupos, que se originaban a partir de la materia de la médula espinal circundante. En conclusión, PHPMA-hydrogel mejora la recuperación de la función locomotora de las patas traseras y promueve el crecimiento regenerativo de las fibras nerviosas. Se requieren más estudios para aclarar el mecanismo del efecto de hidrogel PHPMA.

Local treatment with ascorbic acid accelerates recovery of post-sutured Achilles tendon in male Wistar rats

Tendon rupture is a very frequent accident involving average people and high-performance athletes. Clinical studies describe tendon recovery as a painful and slow process involving different biochemical and histological events. Ascorbic acid (AA) is a potent antioxidant as well as an important cofactor for collagen synthesis. In the current study, we evaluated if local treatment with AA is able to promote tendon repair in tenotomized rats. Animals were submitted to Achilles tendon rupture followed by surgical suture. Control and AA groups received in loco injection of saline solution (0.9% NaCl) and 30 mM AA, respectively. Histological and functional recovery of Achilles tendon tissue was evaluated at 7, 14, and 21 days post-surgery. Hematoxylin/eosin staining and collagen fluorescence analysis showed intense disarrangement of tendon tissue in the saline group. Tenotomized animals also showed hypercellularity in tendon tissue compared with non-tenotomized animals. The Achilles functional index (AFI) showed a significant decrease of tendon functionality in tenotomized animals at 7, 14, and 21 days post-surgery. AA accelerated tissue organization and the recovery of function of the Achilles tendons. The beneficial effect of AA treatment was also observed in the organization of the collagen network. Data presented in the current work showed that in loco treatment with AA accelerated the recovery of injured Achilles tendon post-surgery.

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

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.

Effects of herbal medicine Sijunzi decoction on rabbits after relieving intestinal obstruction

Intestinal obstruction leads to blockage of the movement of intestinal contents. After relieving the obstruction, patients might still suffer with compromised immune function and nutritional deficiency. This study aimed to evaluate the effects of Sijunzi decoction on restoring the immune function and nutritional status after relieving the obstruction. Experimental rabbits (2.5±0.2 kg) were randomly divided into normal control group, 2-day intestinal obstruction group, 2-day natural recovery group, 4-day natural recovery group, 2-day treated group, and 4-day treated group. Sijunzi decoction was given twice a day to the treated groups. The concentration of markers was analyzed to evaluate the immune function and nutritional status. The concentration of interleukin-2, immunoglobulins and complement components of the treated groups were significantly higher than the natural recovery group (P<0.05). The levels of CD4+ and CD4+/CD8+ increased then decreased in the treated groups. The levels of tumor necrosis factor-α and CD8+ were significantly lower than the natural recovery group. The level of total protein in the treated groups also increased then decreased after relieving the obstruction. The levels of albumin, prealbumin and insulin-like growth factor-1 were significantly higher in the treated groups than in the natural recovery group (P<0.05). Transferrin level in the treated groups was significantly higher than the obstruction group (P<0.05). Sijunzi decoction can lessen the inflammatory response and improve the nutrition absorption after relieving the obstruction.

Local inhibition of nitrergic activity in tenotomized rats accelerates muscle regeneration by increasing fiber area and decreasing central core lesions

Muscular atrophy is a progressive degeneration characterized by muscular proteolysis, loss of mass and decrease in fiber area. Tendon rupture induces muscular atrophy due to an intrinsic functional connection. Local inhibition of nitric oxide synthase (NOS) by Nω-nitro-L-arginine methyl ester (L-NAME) accelerates tendon histological recovery and induces functional improvement. Here we evaluate the effects of such local nitrergic inhibition on the pattern of soleus muscle regeneration after tenotomy. Adult male Wistar rats (240 to 280 g) were divided into four experimental groups: control (n=4), tenotomized (n=6), vehicle (n=6), and L-NAME (n=6). Muscular atrophy was induced by calcaneal tendon rupture in rats. Changes in muscle wet weight and total protein levels were determined by the Bradford method, and muscle fiber area and central core lesion (CCL) occurrence were evaluated by histochemical assays. Compared to tenotomized (69.3±22%) and vehicle groups (68.1%±17%), L-NAME treatment induced an increase in total protein level (108.3±21%) after 21 days post-injury. A reduction in fiber areas was observed in tenotomized (56.3±1.3%) and vehicle groups (53.9±3.9%). However, L-NAME treatment caused an increase in this parameter (69.3±1.6%). Such events were preceded by a remarkable reduction in the number of fibers with CCL in L-NAME-treated animals (12±2%), but not in tenotomized (21±2.5%) and vehicle groups (19.6±2.8%). Altogether, our data reveal that inhibition of tendon NOS contributed to the attenuation of atrophy and acceleration of muscle regeneration.

Effect of ozone and methylprednisolone treatment following crush type sciatic nerve injury

ABSTRACT PURPOSE: To assess and compare the histopathological effects of ozone therapy and/or methylprednisolone (MPS) treatment on regeneration after crush type sciatic nerve injury. METHODS: Forty Sprague-Dawley male rats were randomly allocated into four groups. Four groups received the following regimens intraperitoneally every day for 14 days after formation of crush type injury on sciatic nerve: Group I: ozone (20mcg/ml); Group II: methylprednisolone (2mg/kg); Group III: ozone (20 mcg/ml) and methylprednisolone (2mg/kg); Group IV: isotonic saline (0.9%). The histomorphological evaluation was made after biopsies were obtained from the sites of injury. RESULTS: Significant differences were noted between groups in terms of degeneration (p=0.019), nerve sheath cell atrophy (p=0.012), intraneural inflammatory cellular infiltration (p=0.002), perineural granulation tissue formation (p=0.019), perineural vascular proliferation (p=0.004), perineural inflammatory cellular infiltration (p<0.001) and inflammation in peripheral tissue (p=0.006). Degeneration was remarkably low in Group III, while no change in nerve sheath cell was noted in Group II. CONCLUSION: The combined use of methylprednisolone and ozone treatment can have beneficial effects for regeneration after crush type nerve injury.

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.

Effects of ischemia and omeprazole preconditioning on functional recovery of isolated rat heart / Efeitos da isquemia e pré-condicionamento com omeprazol na recuperação funcional do coração isolado de rato

Abstract Objective: The aim of this study was to compare protective effects of ischemic and potential protective effects of pharmacological preconditioning with omeprazole on isolated rat heart subjected to ischemia/reperfusion. Methods: The hearts of male Wistar albino rats were excised and perfused on a Langendorff apparatus. In control group (CG) after stabilization period, hearts were subjected to global ischemia (perfusion was totally stopped) for 20 minutes and 30 minutes of reperfusion. Hearts of group II (IPC) were submitted to ischemic preconditioning lasting 5 minutes before 20 minutes of ischemia and 30 minutes of reperfusion. In third group (OPC) hearts first underwent preconditioning lasting 5 minutes with 100μM omeprazole, and then submitted 20 minutes of ischemia and 30 minutes of reperfusion. Results: Administration of omeprazole before ischemia induction had protective effect on myocardium function recovery especially regarding to values of systolic left ventricular pressure and dp/dt max. Also our findings are that values of coronary flow did not change between OPC and IPC groups in last point of reperfusion. Conclusion: Based on our results it seems that ischemic preconditioning could be used as first window of protection after ischemic injury especially because all investigated parameters showed continuous trend of recovery of myocardial function. On the other hand, preconditioning with omeprazole induced sudden trend of recovery with positive myocardium protection, although less effective than results obtained with ischemic preconditioning not withstand, we must consider that omeprazole may be used in many clinical circumstances where direct coronary clamping for ischemic preconditioning is not possible. .

Resumo Objetivo: O objetivo deste estudo foi comparar os efeitos protetores de efeitos protetores isquêmicos e potenciais de précondicionamento farmacológico com omeprazol no coração isolado de rato submetido à isquemia/reperfusão. Métodos: Os corações de ratos albinos Wistar machos foram excisados e perfundidos em um aparelho de Langendorff. No grupo controle (grupo I), após o período de estabilização, os corações foram submetidos à isquemia global (a perfusão foi totalmente interrompida) por 20 minutos e 30 minutos de reperfusão. Corações do grupo II (IPC) foram submetidos a précondicionamento isquêmico com duração de 5 minutos antes de 20 minutos de isquemia e 30 minutos de reperfusão. No terceiro grupo (OPC), corações foram submetidos a pré-condicionamento com duração de 5 minutos com 100 μM de omeprazol, e, então, submetidos a 20 minutos de isquemia e 30 minutos de reperfusão. Resultados: A administração de omeprazol antes da indução da isquemia teve efeito protetor sobre a recuperação funcional do miocárdio especialmente em relação aos valores de pressão sistólica ventricular esquerda e dp/dt max. Também os nossos achados são de que os valores de fluxo coronário não se alteraram entre os grupos OPC e IPC no último ponto de reperfusão. Conclusão: Com base nos nossos resultados, o pré-condicionamento isquêmico poderia ser usado como primeira janela de proteção após a lesão isquêmica, especialmente porque todos os parâmetros analisados apresentam tendência contínua de recuperação da função do miocárdio. Por outro lado, o pré-condicionamento induzido com omeprazol apresenta tendência repentina de recuperação com proteção miocárdio positiva, embora menos efetiva da obtida com o pré-condicionamento isquêmico. Devemos considerar que o omeprazol pode ser usado em muitas circunstâncias clínicas em que o pinçamento coronariano direto para pré-condicionamento isquêmico não é possível. .

Possible roles of COX-1 in learning and memory impairment induced by traumatic brain injury in mice

People who suffer from traumatic brain injury (TBI) often experience cognitive deficits in spatial reference and working memory. The possible roles of cyclooxygenase-1 (COX-1) in learning and memory impairment in mice with TBI are far from well known. Adult mice subjected to TBI were treated with the COX-1 selective inhibitor SC560. Performance in the open field and on the beam walk was then used to assess motor and behavioral function 1, 3, 7, 14, and 21 days following injury. Acquisition of spatial learning and memory retention was assessed using the Morris water maze on day 15 post-TBI. The expressions of COX-1, prostaglandin E2 (PGE2), interleukin (IL)-6, brain-derived neurotrophic factor (BDNF), platelet-derived growth factor BB (PDGF-BB), synapsin-I, and synaptophysin were detected in TBI mice. Administration of SC560 improved performance of beam walk tasks as well as spatial learning and memory after TBI. SC560 also reduced expressions of inflammatory markers IL-6 and PGE2, and reversed the expressions of COX-1, BDNF, PDGF-BB, synapsin-I, and synaptophysin in TBI mice. The present findings demonstrated that COX-1 might play an important role in cognitive deficits after TBI and that selective COX-1 inhibition should be further investigated as a potential therapeutic approach for TBI.

Effect of Macrophage Migration Inhibitory Factor on Corneal Sensitivity after Laser In Situ Keratomileusis in Rabbit

PURPOSE: To investigate the effect of macrophage migration inhibitory factor (MIF) on corneal sensitivity after laser in situ keratomileusis (LASIK) surgery. METHODS: New Zealand white rabbits were used in this study. A hinged corneal flap (160-microm thick) was created with a microkeratome, and -3.0 diopter excimer laser ablation was performed. Expressions of MIF mRNA in the corneal epithelial cells and surrounding inflammatory cells were analyzed using reverse transcription polymerase chain reaction at 48 hours after LASIK. After LASIK surgery, the rabbits were topically given either 1) a balanced salt solution (BSS), 2) MIF (100 ng/mL) alone, or 3) a combination of nerve growth factor (NGF, 100 ug/mL), neurotrophine-3 (NT-3, 100 ng/mL), interleukin-6 (IL-6, 5 ng/mL), and leukemia inhibitory factor (LIF, 5 ng/mL) four times a day for three days. Preoperative and postoperative corneal sensitivity at two weeks and at 10 weeks were assessed using the Cochet-Bonnet esthesiometer. RESULTS: Expression of MIF mRNA was 2.5-fold upregulated in the corneal epithelium and 1.5-fold upregulated in the surrounding inflammatory cells as compared with the control eyes. Preoperative baseline corneal sensitivity was 40.56 +/- 2.36 mm. At two weeks after LASIK, corneal sensitivity was 9.17 +/- 5.57 mm in the BSS treated group, 21.92 +/- 2.44 mm in the MIF treated group, and 22.42 +/- 1.59 mm in the neuronal growth factors-treated group (MIF vs. BSS, p < 0.0001; neuronal growth factors vs. BSS, p < 0.0001; MIF vs. neuronal growth factors, p = 0.815). At 10 weeks after LASIK, corneal sensitivity was 15.00 +/- 9.65, 35.00 +/- 5.48, and 29.58 +/- 4.31 mm respectively (MIF vs. BSS, p = 0.0001; neuronal growth factors vs. BSS, p = 0.002; MIF vs. neuronal growth factors, p = 0.192). Treatment with MIF alone could achieve as much of an effect on recovery of corneal sensation as treatment with combination of NGF, NT-3, IL-6, and LIF. CONCLUSIONS: Topically administered MIF plays a significant role in the early recovery of corneal sensitivity after LASIK in the experimental animal model.

Effect of melatonin on the functional recovery from experimental traumatic compression of the spinal cord

Spinal cord injury is an extremely severe condition with no available effective therapies. We examined the effect of melatonin on traumatic compression of the spinal cord. Sixty male adult Wistar rats were divided into three groups: sham-operated animals and animals with 35 and 50% spinal cord compression with a polycarbonate rod spacer. Each group was divided into two subgroups, each receiving an injection of vehicle or melatonin (2.5 mg/kg, intraperitoneal) 5 min prior to and 1, 2, 3, and 4 h after injury. Functional recovery was monitored weekly by the open-field test, the Basso, Beattie and Bresnahan locomotor scale and the inclined plane test. Histological changes of the spinal cord were examined 35 days after injury. Motor scores were progressively lower as spacer size increased according to the motor scale and inclined plane test evaluation at all times of assessment. The results of the two tests were correlated. The open-field test presented similar results with a less pronounced difference between the 35 and 50% compression groups. The injured groups presented functional recovery that was more evident in the first and second weeks. Animals receiving melatonin treatment presented more pronounced functional recovery than vehicle-treated animals as measured by the motor scale or inclined plane. NADPH-d histochemistry revealed integrity of the spinal cord thoracic segment in sham-operated animals and confirmed the severity of the lesion after spinal cord narrowing. The results obtained after experimental compression of the spinal cord support the hypothesis that melatonin may be considered for use in clinical practice because of its protective effect on the secondary wave of neuronal death following the primary wave after spinal cord injury.

Efeitos da angiotensina-I e isquemia na recuperação funcional em corações isolados / Effects of angiotensin-I and ischemia on functional recovery in isolated hearts

FUNDAMENTO: A ressuscitação de parada cardíaca pode apresentar disfunção miocárdica determinada pelo tempo da isquemia, e a inibição da enzima conversora de angiotensina (ECA) pode reduzir a disfunção cardíaca durante a reperfusão. OBJETIVO: Investigar os efeitos da angiotensina-I e diferentes períodos de isquemia na recuperação funcional em corações de ratos isolados. MÉTODOS: Os corações isolados de ratos Wistar (n = 45; 250-300 g) foram submetidos a diferentes períodos de isquemia global (20, 25 ou 30 min) e reperfundidos (30 min) com o tampão Krebs-Henseleit, ou com a adição de 400 nmol/L de angiotensina-I, ou com 400 nmol/L de angiotensina-I + 100 µmol/L de captopril durante o período de reperfusão. RESULTADOS: A derivada positiva máxima de pressão (+dP/dt max) e o produto frequência-pressão foram reduzidos nos corações expostos à isquemia de 25 min (~ 73 por cento) e à isquemia de 30 min (~ 80 por cento) vs. isquemia de 20 min. A pressão diastólica final do ventrículo esquerdo (PDFVE) e a pressão de perfusão (PP) foram aumentadas nos corações expostos à isquemia de 25 min (5,5 e 1,08 vezes, respectivamente) e à isquemia de 30 min (6 e 1,10 vezes, respectivamente) vs. isquemia de 20 min. A angiotensina-I ocasionou uma diminuição no +dP/dt max e no produto frequência-pressão (~ 85-94 por cento) em todos os períodos de isquemia e um aumento na PDFVE e na PP (6,9 e 1,25 vezes, respectivamente) apenas na isquemia de 20 min. O captopril foi capaz de reverter parcial ou completamente os efeitos da angiotensina-I na recuperação funcional nas isquemias de 20 e 25 min CONCLUSÃO: Os dados sugerem que a angiotensina-II participa direta ou indiretamente no dano pós-isquêmico e que a capacidade de um inibidor da ECA atenuar esse dano depende do tempo de isquemia.

BACKGROUND: Cardiac arrest resuscitation can present myocardial dysfunction determined by ischemic time, and inhibition of the angiotensin-converting enzyme (ACE) can reduce cardiac dysfunction during reperfusion. OBJECTIVE: To investigate the effects of angiotensin-I and different periods of ischemia on functional recovery in isolated rat hearts. METHODS: Isolated hearts from Wistar rats (n=45; 250-300 g) were submitted to different periods of global ischemia (20, 25 or 30 min) and reperfused (30 min) with Krebs-Henseleit buffer alone or with the addition of 400 nmol/L angiotensin-I, or 400 nmol/L angiotensin-I + 100 mmol/L captopril along the reperfusion period. RESULTS: The maximal positive derivative of pressure (+dP/dt max) and rate-pressure product were reduced in hearts exposed to 25 min ischemia (~73 percent) and 30 min ischemia (~80 percent) vs. 20 min ischemia. Left ventricular end-diastolic pressure (LVEDP) and perfusion pressure (PP) were increased in hearts exposed to 25 min ischemia (5.5 and 1.08 fold, respectively) and 30 min ischemia (6 and 1.10 fold, respectively) vs. 20 min ischemia. Angiotensin-I caused a decrease in +dP/dt max and rate-pressure product (~85-94 percent) in all ischemic periods and an increase in LVEDP and PP (6.9 and 1.25 fold, respectively) only at 20 min ischemia. Captopril was able to partially or completely reverse the effects of angiotensin-I on functional recovery in 20 min and 25 min ischemia. CONCLUSION: These data suggest that angiotensin-II directly or indirectly participates in the post-ischemic damage, and the ability of an ACE inhibitor to attenuate this damage depends on ischemic time.

Pantoprazole provides myocardial protection similar to ischemic preconditioning: experimental study of isolated hearts of rats / Pantoprazol oferece proteção miocárdica semelhante ao pré-condicionamento isquêmico: estudo em corações isolados de ratos

OBJECTIVE: To evaluate pantoprazole effect in the functional recovery of isolated hearts of rats, submitted to ischemia and reperfusion with and without ischemic preconditioning. METHODS: In four groups of eight Wistar breed rats, the hearts were removed after anesthesia and perfused with Krebs-Henseleit solution (95% O2, 5% CO2, 37ºC). GI, GII, GIII and GIV hearts were submitted to ischemia (20 min) and reperfusion (30 min). In GII and GIV, preconditioning was performed with 5 min of ischemia and 5 min of reperfusion before 20 min of the ischemia period induction. In GIII and GIV pantoprazole 100 mg was done before a 20 min-period of ischemia induction. Heart Rate (HR), Coronary Flow (CoF), Systolic Pressure (SP), +dP/dt and -dP/dt were registered before (t0) and after reperfusion (t30). Kruskal-Wallis (P<0.05) test was used. RESULTS: There were no differences (P>0.05) between groups among HR and CoF values. Differences occurred between groups, I and II, III and IV at t30 with SP reduced for 32% mean value in GI, 65% GII, 65% GIII, and 73% GIV; The t30 + dP/dtmax were 34% in GI, 61% GII, 63% GIII and 72% GIV. The t30 -dP/dtmax were GI 28%, GII 63%, GIII 75 % and GIV 75%; (P<0.05). There were no significant differences in the SP, +dP/dtmax, and -dP/dtmax between Groups II, III and IV results. CONCLUSIONS: The administration of pantoprazole before induction of ischemia significantly protected the myocardial functional recovery with the results of SP, + dP / dtmax and dP/dtmax similar to the ischemic preconditioning against ischemia-reperfusion.

OBJETIVO: Avaliar o efeito do pantoprazol na recuperação funcional de corações isolados de ratos submetidos à isquemia e reperfusão com e sem pré-condicionamento isquêmico. MÉTODOS: Em quatro grupos de oito ratos Wistar, após anestesia os corações foram removidos e perfundidos com Krebs-Henseleit (95% O2, 5% CO2, 37ºC). Os corações de GI, GII, GIII e GIV foram submetidos a 20' de isquemia e 30'de reperfusão. Em GII e GIV realizou-se pré condicionamento com 5' de isquemia e 5' de reperfusão antes dos 20' de isquemia. Em GIII e GIV, pantoprazol 100mcg foram injetados imediatamente antes dos 20' de isquemia. Frequência cardíaca (FC), Fluxo Coronariano (FCo), Pressão Sistólica (PS), + dP/dt e -dP/dt foram registrados em (T0) e (t30). Estatística: Kruskal-Wallis (P <0,05). RESULTADOS: Não houve diferenças (P> 0,05) entre grupos nos valores de FC e de CFo. Diferenças (P <0,05) ocorreram entre GI e GII, GIII e GIV, com PS t30 reduzida para 32% GI, 65% GII, 65% GIII e 73% GIV. Em t30 + dP/dtmax 34% GI, 61% GII, 63% GIII e 72% GIV. A -dP/dtmax t30 GI 28%, GII 63%, GIII 75% e GIV 75%. Não houve diferença estatística (P< 0,05) nos valores de PS, +dP/dtmax e -dP/dtmax entre os GII, GIII e GIV. CONCLUSÕES: A administração do pantoprazol antes da indução da isquemia protegeu significativamente a recuperação funcional miocárdica com resultados de SP, +dP/ dtmax e -dP/dtmax semelhantes aos do pré-condicionamento isquêmico contra lesão de isquemia-reperfusão.

Outcomes from intracerebral hemorrhage among patients pre-treated with statins / Prognóstico da hemorragia intracerebral em pacientes previamente tratados com estatinas

OBJECTIVE: 3-hydroxy-3-methylglutaryl coenzyme A (HMG-CoA) reductase inhibitors, or statins, have been associated with improved clinical outcomes after ischemic stroke and subarachnoid hemorrhage, but with an increased risk of incidental spontaneous intracerebral hemorrhage (ICH). We investigated whether the statin use before ICH, was associated with functional independence, 90 days after treatment. METHOD: We analyzed 124 consecutive ICH patients with 90-day outcome data who were enrolled in a prospective cohort study between 2006 and 2009. Eighty-three patients were included in this study. Among ICH survivors, univariate Cox regression models and Kaplan-Meier plots were used to determine subject characteristics that were associated with an increased risk of recurrence. Statin usage was determined through interviewing the patient at the time of ICH and confirmed by reviewing their medical records. Independent status was defined as Glasgow Outcome Scale grades 4 or 5. RESULTS: Statins were used by 20 out of 83 patients (24 percent) before ICH onset. There was no effect from pre-ICH statin use on functional independence rates (28 percent versus 29 percent, P=0.84) or mortality (46 percent versus 45 percent, P=0.93). CONCLUSION: Pre-ICH statin use is not associated with changes to ICH functional outcome or mortality.

OBJETIVO: Inibidores da 3-hydroxy-3-methylglutaryl coenzima A (HMG-CoA) redutase, ou estatinas, têm sido associados com melhora do prognóstico após eventos encefálicos isquêmicos e hemorragia subaracnóidea, mas com um aumento do risco de evento encefálico hemorrágico (AVEh). Nós investigamos se o uso de estatinas prévio ao sangramento é associado com independência funcional em 90 dias. MÉTODO: Analisamos 124 pacientes consecutivos com AVEh com 90 dias de seguimento, selecionando 83 para um estudo coorte prospectivo entre 2006 e 2009. O uso de estatinas foi determinado pela entrevista ao paciente no momento da entrada ao hospital e complementado pela revisão do prontuário. Foi definido como independência funcional um GOS (Glasgow Outcome Scale) 4 ou 5. RESULTADOS: Estatinas eram usadas por 20/83 (24 por cento) antes do AVEh. Não houve efeito benéfico do uso prévio ao AVEh de estatinas nas taxas de independência funcional (28 por cento versus 29 por cento, P=0,84) ou mortalidade (46 por cento versus 45 por cento, P=0,93). CONCLUSÃO: O uso de estatina pré-AVEh não é associado com melhora do prognóstico funcional ou taxa de mortalidade.

Proteção da recuperação funcional do miocárdio pelo omeprazol após isquemia-reperfusão em corações isolados de ratos / Myocardium functional recovery protection by omeprazole after ischemia-reperfusion in isolated rat hearts

OBJETIVO: Analisar efeitos do omeprazol na proteção da recuperação funcional de corações isolados de ratos submetidos à lesão de isquemia-reperfusão. MÉTODOS: Foram estudados 12 ratos Wistar, peso corpóreo médio de 280g. Após anestesia com injeção intra-abdominal de 10mg de cetamina e 2mg de xilazina, os corações foram removidos e mantidos em perfusão com solução Krebs-Henseleit (95 por centoO2 e 5 por cento CO2, 37ºC, 110-120mmHg de pressão de perfusão e pressão diastólica de 8 mmHg) em sistema Langendorff, modificado, descartável, modelo FCSFA-ServCor (Comex Ltda.). Os seis corações do Grupo I (GI) e os seis do Grupo II (GII) foram submetidos a 20 minutos de isquemia e 30 minutos de reperfusão. Nos corações do Grupo II, imediatamente antes da isquemia, foram administrados via perfusão coronária 200mcg de omeprazol. Foram controlados frequência cardíaca (FC), fluxo coronário (FCo), pressão sistólica (PS), +dP/dt e -dP/dt, após estabilização (t0) e no final da reperfusão (t30). Empregou-se método não paramétrico de Kruskal-Wallis (P<0,05) para análise estatística dos dados. RESULTADOS: Não ocorreram diferenças (P>0,05) entre os valores de FCo e FC nos dois grupos. No final do período de reperfusão (t30), foram significantes (P<0,05) as variações da PS reduzida para 28,0±3,6 por cento do valor inicial (t0) no Grupo I e para 79.0±5,9 por cento no Grupo II; a +dP/dtmax declinou para 31,0±5,6 por cento no GI, mantendo-se em 99,4±11,2 por cento (P<0,05) no GII e a -dP/dtmax declinou para 26,0±7,3 por cento no GI, mantendo-se em 82,0±2, 2 por cento no GII (P<0,05). CONCLUSÃO: A administração do omeprazol antes da indução da isquemia coronária protegeu significantemente a recuperação funcional do miocárdio.

OBJECTIVE: To evaluate the myocardium contractility alterations of isolated hearts of rats, submitted to ischemia and reperfusion with and without administration of the omeprazole. METHODS: Twelve Wistar breed rats with 270g mean body weight was studied. After anesthesia by intraperitoneal injection of ketamine 10mg and xylazine 2mg, their hearts were removed and perfused with Krebs-Henseleit solution (95 percent of O2 and 5 percent of CO2, 37ºC, 110-120 mmHg perfusion pressure, 8 mmHg ventricular diastolic pressure) in the São Francisco de Assis disposable Langendorff system model Comex Ltda, MG. The six hearts of Group I (GI) and of the Group II (GII) were submitted to 20 min ischemia and 30 min reperfusion. In GII hearts, intracoronary injection of omeprazole 200 mcg was done immediately before the ischemia period induction. The following parameters were registered after the stabilization period (t0), and after the reperfusion period (t30): heart rate (HR), coronary flow (CoF), systolic pressure (SP), +dP/dt and -dP/dt. The Kruskal-Wallis test (P<0.05) was applied to statistical analysis. RESULTS: There were no significant differences (P>0.05) between groups among HR and CoF values. Differences (P<0.05) occurred between groups, I e II after the reperfusion period (t30) regarding systolic pressure reduced for 28.0±3.6 percent in the control group GI and for 79.0±5.9 percent in GII; The +dP/dtmax declined to be only 31.0±5.6 percent in GI, preserving 99.4±11.2 percent values in GII (P<0.05). The t30 -dP/dtmax values were GI 26.0±7.3 percent and GII 82.0±2.2 percent (P<0.05). CONCLUSION: The omeprazole administration before ischemia induction significantly protected the myocardium function recovery.

Chlorpheniramine impairs functional recovery in Carassius auratus after telencephalic ablation

We determined the effect of an H1 receptor antagonist on the functional recovery of Carassius auratus submitted to telencephalic ablation. Five days after surgery the fish underwent a spatial-choice learning paradigm test. The fish, weighing 6-12 g, were divided into four groups: telencephalic ablation (A) or sham lesion (S) and saline (SAL) or chlorpheniramine (CPA, ip, 16 mg/kg). For eight consecutive days each animal was trained individually in sessions separated by 24 h (alternate days). Training trials (T1-T8) consisted of finding the food in one of the feeders, which were randomly blocked for each subject. Animals received an intraperitoneal injection of SAL or CPA 10 min after the training trials. The time spent by the animals in each group to find the food (latency) was analyzed separately at T1 and T8 by the Kruskal-Wallis test, followed by the Student Newman-Keuls test. At T1 the latencies (mean ± SEM) of the A-SAL (586.3 ± 13.6) and A-CPA (600 ± 0) groups were significantly longer than those of the S-SAL (226.14 ± 61.15) and S-CPA (356.33 ± 68.8) groups. At T8, the latencies of the A-CPA group (510.11 ± 62.2) remained higher than those of the other groups, all of which showed significantly shorter latencies (A-SAL = 301.91 ± 78.32; S-CPA = 191.58 ± 73.03; S-SAL = 90.28 ± 41) compared with T1. These results support evidence that training can lead to functional recovery of spatial-choice learning in telencephalonless fish and also that the antagonist of the H1 receptor impairs it.