Your browser doesn't support javascript.
loading
Mostrar: 20 | 50 | 100
Resultados 1 - 8 de 8
Filtrar
1.
Nature ; 490(7419): 187-91, 2012 Oct 11.
Artigo em Inglês | MEDLINE | ID: mdl-23060188

RESUMO

The US National Institute of Neurological Disorders and Stroke convened major stakeholders in June 2012 to discuss how to improve the methodological reporting of animal studies in grant applications and publications. The main workshop recommendation is that at a minimum studies should report on sample-size estimation, whether and how animals were randomized, whether investigators were blind to the treatment, and the handling of data. We recognize that achieving a meaningful improvement in the quality of reporting will require a concerted effort by investigators, reviewers, funding agencies and journal editors. Requiring better reporting of animal studies will raise awareness of the importance of rigorous study design to accelerate scientific progress.


Assuntos
Editoração/normas , Projetos de Pesquisa/normas , Animais , Editoração/tendências , Distribuição Aleatória , Tamanho da Amostra , Estatística como Assunto
2.
J Neurosci ; 22(17): 7526-35, 2002 Sep 01.
Artigo em Inglês | MEDLINE | ID: mdl-12196576

RESUMO

Inflammation in general and proteinases generated as a result are likely mediators of early secondary pathogenesis after spinal cord injury. We report that matrix metalloproteinase-9 (MMP-9) plays an important role in blood-spinal cord barrier dysfunction, inflammation, and locomotor recovery. MMP-9 was present in the meninges and neurons of the uninjured cord. MMP-9 increased rapidly after a moderate contusion spinal cord injury, reaching a maximum at 24 hr, becoming markedly reduced by 72 hr, and not detectable at 7 d after injury. It was seen in glia, macrophages, neutrophils, and vascular elements in the injured spinal cord at 24 hr after injury. The natural tissue inhibitors of MMPs were unchanged over this time course. MMP-9-null mice exhibited significantly less disruption of the blood-spinal cord barrier, attenuation of neutrophil infiltration, and significant locomotor recovery compared with wild-type mice. Similar findings were observed in mice treated with a hydroxamic acid MMP inhibitor from 3 hr to 3 d after injury, compared with the vehicle controls. Moreover, the area of residual white matter at the lesion epicenter was significantly greater in the inhibitor-treated group. This study provides evidence that MMP-9 plays a key role in abnormal vascular permeability and inflammation within the first 3 d after spinal cord injury, and that blockade of MMPs during this critical period attenuates these vascular events and leads to improved locomotor recovery. Our findings suggest that early inhibition of MMPs may be an efficacious strategy for the spinal cord-injured patient.


Assuntos
Metaloproteinases da Matriz/metabolismo , Recuperação de Função Fisiológica , Traumatismos da Medula Espinal/fisiopatologia , Medula Espinal/irrigação sanguínea , Medula Espinal/fisiopatologia , Animais , Astrócitos/metabolismo , Astrócitos/patologia , Vasos Sanguíneos/metabolismo , Vasos Sanguíneos/patologia , Permeabilidade Capilar , Modelos Animais de Doenças , Progressão da Doença , Ativação Enzimática/efeitos dos fármacos , Inibidores Enzimáticos/farmacologia , Imuno-Histoquímica , Macrófagos/metabolismo , Macrófagos/patologia , Masculino , Metaloproteinase 9 da Matriz/deficiência , Metaloproteinase 9 da Matriz/metabolismo , Inibidores de Metaloproteinases de Matriz , Metaloproteinases da Matriz/deficiência , Meninges/metabolismo , Meninges/patologia , Camundongos , Camundongos Knockout , Atividade Motora/efeitos dos fármacos , Neurônios Motores/metabolismo , Neurônios Motores/patologia , Infiltração de Neutrófilos/efeitos dos fármacos , Recuperação de Função Fisiológica/efeitos dos fármacos , Medula Espinal/patologia , Traumatismos da Medula Espinal/tratamento farmacológico , Traumatismos da Medula Espinal/patologia
3.
J Neurotrauma ; 32(22): 1725-35, 2015 Nov 15.
Artigo em Inglês | MEDLINE | ID: mdl-26058402

RESUMO

Traumatic brain injury (TBI) is a major public health issue exacting a substantial personal and economic burden globally. With the advent of "big data" approaches to understanding complex systems, there is the potential to greatly accelerate knowledge about mechanisms of injury and how to detect and modify them to improve patient outcomes. High quality, well-defined data are critical to the success of bioinformatics platforms, and a data dictionary of "common data elements" (CDEs), as well as "unique data elements" has been created for clinical TBI research. There is no data dictionary, however, for preclinical TBI research despite similar opportunities to accelerate knowledge. To address this gap, a committee of experts was tasked with creating a defined set of data elements to further collaboration across laboratories and enable the merging of data for meta-analysis. The CDEs were subdivided into a Core module for data elements relevant to most, if not all, studies, and Injury-Model-Specific modules for non-generalizable data elements. The purpose of this article is to provide both an overview of TBI models and the CDEs pertinent to these models to facilitate a common language for preclinical TBI research.


Assuntos
Lesões Encefálicas , Elementos de Dados Comuns , Bases de Dados Factuais , Animais , Traumatismos por Explosões/patologia , Hemorragia Encefálica Traumática/patologia , Lesões Encefálicas/patologia , Biologia Computacional , Humanos , Laboratórios , Metanálise como Assunto , Modelos Animais , Modelos Neurológicos , Saúde Pública , Padrões de Referência
4.
J Neurotrauma ; 20(5): 437-45, 2003 May.
Artigo em Inglês | MEDLINE | ID: mdl-12803976

RESUMO

Children younger than 4 years old have worse outcome after traumatic brain injury (TBI) compared to older children and adults. This increased susceptibility may in part be due to differences in the response to oxidative stress. We hypothesized that the immature brain does not have an adequate compensatory response to injury from oxidative stress. To begin to address this hypothesis, we first compared the general dimensions and water content in postnatal day 21 (P21) and adult murine brain in the naive state as well as after injury (edema). We examined glutathione peroxidase (GPx ) activity in cortical and subcortical regions in P21 and adult murine brain following a controlled cortical impact. Brain dimensions including areas of the mantle and hemispheres were similar in each of these groups. The thickness of the cortical mantle was significantly greater in the immature brain as compared to the mature brain (p = 0.01, respectively). Brain edema was assessed through changes in water content, and the response to oxidative challenge was identified by changes in GPx activity. The P21 brain was similar in vulnerability to posttraumatic brain edema when compared to adult. GPx activity in the adult brain was increased within 24 h post-injury in the cortex, thalamus and hippocampus (ANOVA, p < 0.05), whereas there was no compensatory increase in GPx activity in P21 brain, although baseline levels had reached adult levels developmentally. These findings support our hypothesis and illuminate the important role of oxidative stress after TBI in the immature brain that warrants further study.


Assuntos
Edema Encefálico/patologia , Lesões Encefálicas/patologia , Encéfalo/crescimento & desenvolvimento , Encéfalo/metabolismo , Glutationa Peroxidase/metabolismo , Fatores Etários , Animais , Barreira Hematoencefálica/fisiologia , Encéfalo/anatomia & histologia , Encéfalo/patologia , Química Encefálica , Edema Encefálico/etiologia , Lesões Encefálicas/complicações , Masculino , Camundongos , Camundongos Endogâmicos C57BL , Fatores de Tempo
5.
Neurosci Lett ; 336(1): 13-6, 2003 Jan 09.
Artigo em Inglês | MEDLINE | ID: mdl-12493591

RESUMO

Induction of heme oxygenase-1 (HO-1) in the spinal cord was studied in adult wildtype and transgenic mice overexpressing the antioxidant copper, zinc superoxide dismutase (CuZn SOD) 24 h after intrathecal infusion of heterologous lysed blood. Double immunolabeling techniques were used to determine the extent to which HO-1 was induced in astrocytes and microglia/macrophages. HO-1 was induced in both astrocytes and microglia/macrophages in the dorsal horns near the site of infusion of lysed blood in all mice. However, the number of HO-1 labeled cells was significantly less in the transgenic as compared to the wildtype animals. Together, these findings suggest that lysed blood preferentially induces HO-1 in glia and macrophages through the generation of oxidative stress.


Assuntos
Proteínas Sanguíneas/farmacologia , Sangue , Heme Oxigenase (Desciclizante)/metabolismo , Superóxido Dismutase/efeitos dos fármacos , Animais , Antígeno CD11b/metabolismo , Ativação Enzimática/fisiologia , Proteína Glial Fibrilar Ácida/metabolismo , Heme Oxigenase-1 , Imuno-Histoquímica , Injeções Espinhais , Proteínas de Membrana , Camundongos , Camundongos Transgênicos , Estresse Oxidativo/fisiologia , Distribuição Aleatória , Medula Espinal/irrigação sanguínea , Medula Espinal/citologia , Medula Espinal/enzimologia , Superóxido Dismutase/genética
6.
J Neurosci Res ; 73(5): 644-58, 2003 Sep 01.
Artigo em Inglês | MEDLINE | ID: mdl-12929132

RESUMO

Normal adult uninjured nerve is unable to support axonal regeneration. We have studied the mechanisms underlying the regeneration of peripheral nerve by culturing adult mouse dorsal root ganglia (DRG) explants on unfixed, longitudinal cryosections of either the uninjured sciatic nerve or the distal segment of the transected sciatic nerve. We found that, initially, DRG grew vigorously on cryosections of both uninjured and postinjury sciatic nerves. However, the neurites began to degenerate shortly after contact with the uninjured nerve, whereas those growing on postinjury nerve substrate remained healthy for up to 9 days in culture. This ability to support stable outgrowth peaked at 8 days, gradually decreased by 10 days, and disappeared by 20 days after injury. Macrophages appeared in the distal segment by 4 days postinjury and had infiltrated its entire length by 8 days. Uninjured nerve cryosections could be rendered supportive of stable outgrowth by preincubation with macrophage-conditioned medium or by brief trypsinization. The activity of the macrophage-conditioned medium was augmented upon activation of macrophages. Together these findings suggest that the environment of the sciatic nerve undergoes a transformation during Wallerian degeneration such that it becomes transiently supportive of the stable outgrowth of neurites. This transformation may be mediated by a proteolytic activity, generated by activated macrophages, that removes a putative "degeneration signal" protein normally present in the adult nerve and thus contributes to the maintenance of stable regenerating neurites.


Assuntos
Macrófagos/fisiologia , Regeneração Nervosa/fisiologia , Neuritos/fisiologia , Nervo Isquiático/fisiologia , Animais , Axotomia , Meios de Cultivo Condicionados , Feminino , Gânglios Espinais/fisiologia , Imuno-Histoquímica , Camundongos , Fatores de Crescimento Neural/metabolismo , Técnicas de Cultura de Órgãos , Nervo Isquiático/lesões , Fatores de Tempo
7.
Exp Neurol ; 176(1): 105-16, 2002 Jul.
Artigo em Inglês | MEDLINE | ID: mdl-12093087

RESUMO

We characterized the regional and temporal patterns of neuronal injury and axonal degeneration after controlled cortical impact of moderate severity in mice at postnatal day 21. Animals were euthanized at 1, 3, or 7 days after injury or sham operation. The brains were removed and prepared for immunolocalization of neurons and microglia/macrophages or subjected to Fluoro-Jade and silver stains, indicators of irreversible neuronal cell injury and axonal degeneration. There was significant neuronal loss in both the ipsi- and the contralateral cortices, ipsilateral hippocampus, and ipsilateral thalamus by 7 days post injury compared to sham-operated animals. Activated microglia/macrophages were most prominent in regions of neuronal loss including the ipsilateral cortex, hippocampus, and thalamus. Neuronal injury, as evidenced by Fluoro-Jade labeling, was not apparent in sham-operated animals. In injured animals, labeling was identified in the ipsilateral cortex and hippocampus at 1 and 3 days post injury. Silver- and Fluoro-Jade-labeled degenerating axons were observed in the ipsilateral subcortical white matter by 1 day post injury, in the ipsilateral external capsule, caudate putamen, and contralateral subcortical white matter by 3 days post injury, and in the internal capsule, pyramidal tracts, and cerebellar peduncles by 7 days post injury. Our findings demonstrate that controlled cortical impact in the developing brain generates neuronal loss in both the ipsilateral and the contralateral cortex, a temporally distinct pattern of subcortical neuronal injury/death, and widespread white matter damage. These observations serve as an important baseline for studying human brain injury and optimizing therapies for the brain-injured child.


Assuntos
Lesões Encefálicas/patologia , Encéfalo/patologia , Fatores Etários , Animais , Axônios/patologia , Núcleo Caudado/patologia , Contagem de Células , Cerebelo/patologia , Córtex Cerebral/patologia , Modelos Animais de Doenças , Progressão da Doença , Corantes Fluorescentes , Hipocampo/patologia , Imuno-Histoquímica , Macrófagos/patologia , Masculino , Camundongos , Camundongos Endogâmicos C57BL , Microglia/patologia , Neurônios/patologia , Putamen/patologia , Tálamo/patologia
8.
J Neurosci Res ; 75(3): 391-400, 2004 Feb 01.
Artigo em Inglês | MEDLINE | ID: mdl-14743452

RESUMO

The neurosteroid dehydroepiandrosterone (DHEA) has neuroprotective properties after ischemic and excitatory insults to the brain. In the developing embryo, it is produced in discrete regions of the central nervous system (CNS), where it specifically promotes axonal growth of differentiated neurons. To test if DHEA could be beneficial after spinal cord injury (SCI), we used a model of moderate contusive SCI developed and characterized in the mouse. Immediately after surgery, we applied treatment with DHEA or with vehicle only and compared treatment groups (n = 12 in each group) over a 42-day period. Locomotor recovery was assessed in an open field using a standardized 21-point scale, according to gait analysis on paw print recordings and using foot fault analyses on an inclined ladder beam. The DHEA-treated group showed improved function compared to vehicle-treated animals in these tests. More strikingly, DHEA enhanced recovery of left-right coordination and fine motor control. In an attempt to correlate functional recovery with spinal cord neuropathology in the different experimental groups, we studied the area of spared white matter at the epicenter and reactive gliosis/scar formation 42 days post-injury (DPI). DHEA significantly increased the area of white matter spared at the epicenter and reduced the area of reactive gliosis surrounding the lesion. These data demonstrate the effectiveness of DHEA in promoting functional recovery in the adult murine injured spinal cord.


Assuntos
Desidroepiandrosterona/uso terapêutico , Atividade Motora/efeitos dos fármacos , Fármacos Neuroprotetores/uso terapêutico , Traumatismos da Medula Espinal/tratamento farmacológico , Traumatismos da Medula Espinal/patologia , Animais , Feminino , Proteína Glial Fibrilar Ácida/metabolismo , Imuno-Histoquímica , Camundongos , Recuperação de Função Fisiológica/efeitos dos fármacos
SELEÇÃO DE REFERÊNCIAS
DETALHE DA PESQUISA