RESUMEN
Oxygen-derived free radicals have been postulated to be involved in brain edema and cell death secondary to ischemia and traumatic injury. Using a model of vasogenic brain edema produced by a permanent occlusion of the left MCA in rats, we have studied the role of superoxide radicals in pathogenesis of ischemic edema. The levels of NBF in ischemic brain were increased by 222%, 420%, and 614%, respectively, at 1, 4, and 24 hr after the MCAO. Topical application of superoxide dismutase to the injured cortex through a modified cranial window significantly reduced the NBF levels, indicating the involvement of superoxide radicals in ischemic brain. Liposome-entrapped SOD, when IV injected 5 min after the MCAO, significantly reduced the degree of edema at 24 hr. Our data indicate that superoxide radicals play an important role in the pathogenesis of vasogenic edema in cerebral ischemia.
Asunto(s)
Edema Encefálico/etiología , Isquemia Encefálica/complicaciones , Superóxidos/metabolismo , Animales , Agua Corporal/análisis , Química Encefálica , Edema Encefálico/metabolismo , Edema Encefálico/fisiopatología , Isquemia Encefálica/metabolismo , Radicales Libres , Liposomas , Masculino , Ratas , Ratas Endogámicas , Superóxido Dismutasa/administración & dosificación , Superóxido Dismutasa/uso terapéuticoAsunto(s)
Ácidos Araquidónicos/fisiología , Astrocitos/metabolismo , Edema Encefálico/metabolismo , Lesiones Encefálicas/metabolismo , Corteza Cerebral/metabolismo , Peroxidación de Lípido , Superóxidos/metabolismo , Animales , Ácido Araquidónico , Ácidos Araquidónicos/farmacología , Astrocitos/efectos de los fármacos , Edema Encefálico/etiología , Células Cultivadas , Corteza Cerebral/efectos de los fármacos , Modelos Animales de Enfermedad , Ratas , Ratas Endogámicas , Superóxido Dismutasa/metabolismoRESUMEN
Traumatic spinal cord injury has recently been shown to cause a rapid increase in free fatty acids (FFAs) and lipid degradation in cats. The present studies report a more delayed, time-dependent increase in FFAs and a concomitant decrease in phospholipids following traumatic spinal injury in rats. The largest percentage increases were found for polyunsaturated fatty acids, particularly arachidonic acid. Associated with these changes were a reduction in the activity of Na+,K+-ATPase and development of spinal cord edema. These findings support the hypothesis that traumatic spinal cord injury leads to delayed, as well as early, hydrolysis of membrane phospholipids, resulting in the liberation of FFAs. Such changes may contribute to secondary spinal cord injury either through direct effects on membranes or through the actions of secondary metabolic products such as the eicosanoids. The latter may cause tissue injury by contributing to the reduction in spinal cord blood flow or through inflammatory responses that follow trauma.
Asunto(s)
Agua Corporal/metabolismo , Ácidos Grasos no Esterificados/metabolismo , ATPasa Intercambiadora de Sodio-Potasio/metabolismo , Traumatismos de la Médula Espinal/metabolismo , Animales , Ácidos Grasos Insaturados/metabolismo , Ácido Palmítico , Ácidos Palmíticos/metabolismo , Fosfatidilcolinas/metabolismo , Fosfatidiletanolaminas/metabolismo , Fosfatidilserinas/metabolismo , Ratas , Ácidos Esteáricos/metabolismo , Factores de TiempoRESUMEN
Oxygen-derived free radicals and membrane lipid peroxidation have been postulated to be involved in brain edema and cell death, secondary to ischemia and traumatic injury. Using a model of brain edema induced by cold-induced injury, we have demonstrated an early elevation of superoxide radicals followed by permeability changes in the blood-brain barrier and development of edema in injured brain. Intravenous injection of liposome-entrapped copper-zinc-superoxide dismutase 5 minutes before the injury-enhanced entry of the enzyme into endothelial cells of the blood-brain barrier of injured brain reduced the brain level of superoxide radicals and ameliorated blood-brain barrier permeability changes and brain edema. Identical treatment 5 minutes after injury was also effective. These data demonstrate that superoxide radicals play an important role in the delayed development of vasogenic brain edema following brain injury.
Asunto(s)
Edema Encefálico/prevención & control , Lesiones Encefálicas/tratamiento farmacológico , Superóxido Dismutasa/uso terapéutico , Animales , Barrera Hematoencefálica , Química Encefálica , Lesiones Encefálicas/metabolismo , Frío/efectos adversos , Radicales Libres , Liposomas/administración & dosificación , Ratas , Superóxido Dismutasa/administración & dosificación , Superóxidos/análisisRESUMEN
We studied the cerebral effects of oxygen-derived free radicals generated from the xanthine oxidase/hypoxanthine/ADP-Fe3+ system. Xanthine oxidase/hypoxanthine/ADP-Fe3+ solution (0.1 ml) was infused into caudate putamen, and brain was frozen rapidly in situ. Brain water and sodium content increased concomitant with decreased potassium content at 24 hours and 48 hours after the infusion. The degree of brain edema and injury depended on the dose of xanthine oxidase. Spongy neuropil and neuronal cytoplasmic vacuoles were seen at 2 hours, with an infiltration by polymorphonuclear leukocytes at 24 hours, followed by lipid-laden macrophages and reactive astrocytes. Leakage of fluorescent dye into neuropil was seen at 2 hours, but not later. These data suggest that oxygen-derived free radicals damage endothelial cells of the blood-brain barrier; the brain injury is characterized by edema and by structural damage of neurons and glia.
Asunto(s)
Encefalopatías/inducido químicamente , Edema Encefálico/inducido químicamente , Permeabilidad Capilar/efectos de los fármacos , Hipoxantinas/farmacología , Xantina Oxidasa/farmacología , Adenosina Difosfato/farmacología , Animales , Barrera Hematoencefálica , Encéfalo/patología , Encefalopatías/metabolismo , Edema Encefálico/metabolismo , Radicales Libres/farmacología , Hipoxantina , Hierro/farmacología , Masculino , Oxígeno/farmacología , Ratas , Ratas EndogámicasRESUMEN
Development of brain edema following various pathological insults occurs after some delay. The mechanism of the delay is poorly understood. Using an in vivo model of cold-injury to study the time course of edema development, the present study indicates that the initiation of phospholipid degradation and rapid release of endogenous polyunsaturated fatty acids occurs within 1 min. Evans blue staining was slightly increased in the lesioned area at 1 min and was more profound at 30 min and at 24 h. The cerebral water content was unchanged at 1 min but was significantly increased at later times. The content of thiobarbituric acid-reactive malondialdehyde (MDA) was normal at 1 min but decreased at 30 min and at 24 h. The lipid-soluble fluorescence of MDA conjugates was also decreased concomitant with the degradation of membrane phospholipids at 24 h. Furthermore, Na+, K+-ATPase activities were consistently decreased in traumatized cortex from 24 h to 48 h after the cold-injury. These data indicate that the degradation of membrane phospholipids, the rapid release of polyunsaturated fatty acids and increased blood-brain barrier permeability are very early events underlying the subsequent development of vasogenic edema induced by cold-injury.