RESUMO
Studies in cocaine-dependent human subjects have shown differences in white matter on diffusion tensor imaging (DTI) compared with non-drug-using controls. It is not known whether the differences in fractional anisotropy (FA) seen on DTI in white matter regions of cocaine-dependent humans result from a pre-existing predilection for drug use or purely from cocaine abuse. To study the effect of cocaine on brain white matter, DTI was performed on 24 rats after continuous infusion of cocaine or saline for 4 weeks, followed by brain histology. Voxel-based morphometry analysis showed an 18% FA decrease in the splenium of the corpus callosum (CC) in cocaine-treated animals relative to saline controls. On histology, significant increase in neurofilament expression (125%) and decrease in myelin basic protein (40%) were observed in the same region in cocaine-treated animals. This study supports the hypothesis that chronic cocaine use alters white matter integrity in human CC. Unlike humans, where the FA in the genu differed between cocaine users and non-users, the splenium was affected in rats. These differences between rodent and human findings could be due to several factors that include differences in the brain structure and function between species and/or the dose, timing, and duration of cocaine administration.
Assuntos
Encéfalo/efeitos dos fármacos , Transtornos Relacionados ao Uso de Cocaína/patologia , Imagem de Difusão por Ressonância Magnética , Processamento de Imagem Assistida por Computador , Animais , Encéfalo/patologia , Cocaína/farmacocinética , Transtornos Relacionados ao Uso de Cocaína/sangue , Corpo Caloso/efeitos dos fármacos , Corpo Caloso/patologia , Dominância Cerebral/fisiologia , Bombas de Infusão Implantáveis , Masculino , Microscopia de Fluorescência , Proteína Básica da Mielina/análise , Fibras Nervosas Mielinizadas/efeitos dos fármacos , Fibras Nervosas Mielinizadas/patologia , Proteínas de Neurofilamentos/análise , Ratos , Ratos Sprague-DawleyRESUMO
Compromised blood-spinal cord barrier (BSCB) is a factor in the outcome following traumatic spinal cord injury (SCI). Vascular endothelial growth factor (VEGF) is a potent stimulator of angiogenesis and vascular permeability. The role of VEGF in SCI is controversial. Relatively little is known about the spatial and temporal changes in the BSCB permeability following administration of VEGF in experimental SCI. Dynamic contrast-enhanced magnetic resonance imaging (DCE-MRI) studies were performed to noninvasively follow spatial and temporal changes in the BSCB permeability following acute administration of VEGF in experimental SCI over a post-injury period of 56 days. The DCE-MRI data was analyzed using a two-compartment pharmacokinetic model. Animals were assessed for open field locomotion using the Basso-Beattie-Bresnahan score. These studies demonstrate that the BSCB permeability was greater at all time points in the VEGF-treated animals compared to saline controls, most significantly in the epicenter region of injury. Although a significant temporal reduction in the BSCB permeability was observed in the VEGF-treated animals, BSCB permeability remained elevated even during the chronic phase. VEGF treatment resulted in earlier improvement in locomotor ability during the chronic phase of SCI. This study suggests a beneficial role of acutely administered VEGF in hastening neurobehavioral recovery after SCI.
Assuntos
Barreira Hematoencefálica/metabolismo , Traumatismos da Medula Espinal/metabolismo , Medula Espinal/metabolismo , Fator A de Crescimento do Endotélio Vascular/metabolismo , Análise de Variância , Animais , Barreira Hematoencefálica/efeitos dos fármacos , Barreira Hematoencefálica/patologia , Imuno-Histoquímica , Imageamento por Ressonância Magnética , Masculino , Modelos Biológicos , Atividade Motora , Permeabilidade , Ratos , Ratos Sprague-Dawley , Medula Espinal/patologia , Traumatismos da Medula Espinal/patologia , Traumatismos da Medula Espinal/terapia , Fator A de Crescimento do Endotélio Vascular/uso terapêuticoRESUMO
After a primary traumatic injury, spinal cord tissue undergoes a series of pathobiological changes, including compromised blood-spinal cord barrier (BSCB) integrity. These vascular changes occur over both time and space. In an experimental model of spinal cord injury (SCI), longitudinal dynamic contrast-enhanced MRI (DCE-MRI) studies were performed up to 56 days after SCI to quantify spatial and temporal changes in the BSCB permeability in tissue that did not show any visible enhancement on the post-contrast MRI (non-enhancing tissue). DCE-MRI data were analyzed using a two-compartment pharmacokinetic model. These studies demonstrate gradual restoration of BSCB with post-SCI time. However, on the basis of DCE-MRI, and confirmed by immunohistochemistry, the BSCB remained compromised even at 56 days after SCI. In addition, open-field locomotion was evaluated using the 21-point Basso-Beattie-Bresnahan scale. A significant correlation between decreased BSCB permeability and improved locomotor recovery was observed.
