A Mechanistic Analysis of Nondisruptive Axonal Injury: A Review

Maxwell, William L.; Povlishock, John T.; Graham, David L.

doi:10.1089/neu.1997.14.419

Cited by 523 publications

(326 citation statements)

References 94 publications

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“…Las fuerzas mecánicas iniciales del trauma pueden lesionar directamente los axones 77,90 mientras que el edema cerebral difuso suele ser máximo entre el tercer y quinto día tras el TCE. La LAD se debe a la lesión de los axones por el trauma, que produce un fallo en el transporte axonal 96 .…”

Section: Figura 1 Tipos De Lesiones Cerebrales Post-traumáticas Agudunclassified

Modelos experimentales de traumatismo craneoencefálico

et al. 2009

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Recibido:225 Neurocirugía 2009; 20: Resumen Objetivo. El objetivo de este trabajo es proporcionar una revisión de los diversos modelos experimentales de traumatismo craneoencefálico (TCE) que se han desarrollado para la investigación del daño cerebral traumático tanto en condiciones in vivo como in vitro, así como detallar los principales conocimientos fisiopatológicos obtenidos a partir de su aplicación. Se expone de forma sintética tanto el tipo de lesión cerebral traumática que cada modelo reproduce como los detalles técnicos necesarios para su utilización por investigadores en el campo del trauma cerebral.Desarrollo. El pronóstico de los pacientes que han sufrido un TCE ha mejorado gracias a las medidas iniciales de estabilización hemodinámica y control de la vía aérea, pero no existe todavía ningún tratamiento específico y eficaz para detener o limitar las lesiones cerebrales causadas por el traumatismo, exceptuando las medidas de control de la presión arterial y la presión intracraneal. Entender la fisiopatología del TCE es el paso básico y fundamental para desarrollar posibles abordajes terapéuticos con aplicación clínica. El daño cerebral traumático en humanos es una patología heterogénea y muy compleja. Por ello, cada modelo experimental se ha desarrollado con el objetivo de reproducir un tipo concreto de las diferentes lesiones cerebrales observadas en pacientes tras un TCE. El uso de estos modelos ha permitido ampliar el conocimiento sobre la fisiopatología del daño cerebral traumático, incluyendo las alteraciones inducidas a nivel celular y molecular.Conclusión. Los modelos experimentales suponen actualmente la mejor herramienta para el estudio de los mecanismos subyacentes a las lesiones cerebrales traumáticas, pero su simplicidad y por lo tanto su incapacidad de reproducir exactamente el daño heterogéneo observado en la práctica clínica puede ser uno de los motivos que explique la discrepancia en la respuesta terapéutica entre los estudios experimentales y clínicos.PALABRAS CLAVE: TCE. Daño cerebral traumático. Edema cerebral. Contusión cerebral. Modelos experimentales. Experimental models of traumatic brain injury SummaryAim. To provide a summary of the different experimental models of traumatic brain injury (TBI) designed under both in vivo and in vitro conditions. A comprehensible review of the specific types of brain lesions induced, as well as the technical details to reproduce each model at the laboratory is given.Development. Outcome of patients suffering from a TBI has significantly improved with the rapid application of vital supporting measures in addition to a strict control of blood and intracranial pressure at the intensive care units. However no specific treatment for post-traumatic brain lesions has proven as efficacious in the clinical settings. A deeper knowlegde of the physiopathological events associated with TBI is necessary for the development of new specific therapies. Due to the heterogeneity of the human TBI, each experimental model has been designed to reproduce a diffe...

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Section: Figura 1 Tipos De Lesiones Cerebrales Post-traumáticas Agudunclassified

Modelos experimentales de traumatismo craneoencefálico

et al. 2009

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“…In the United States alone, 2.5-6.5 million survivors suffer from the physical, psychological and economical consequences of TBI, and a large number of TBI victims have significant long-term deficits in information processing, perceptual function and memory (Consensus conference, 1999;Levin, 1995Levin, , 1998. Axonal damage with widespread distribution, termed diffuse axonal injury (DAI), is an important contributor to the morbidity and mortality seen both clinically and in experimental TBI (Adams et al, 1989;Pierce et al, 1996;Maxwell et al, 1997;Christman et al, 1997), and is characterized by axonal swelling and, ultimately, disconnection. The intracellular DNA fragmentation that has been observed in white matter tracts of TBI patients for up to a year post-injury, may also contribute to continuing damage of the white matter tracts and be linked to the observed progressive atrophy with enlargement of the cerebral ventricles (Williams et al, 2001;Shiozaki et al, 2001).…”

Section: Introductionmentioning

confidence: 99%

Selective temporal and regional alterations of Nogo-A and small proline-rich repeat protein 1A (SPRR1A) but not Nogo-66 receptor (NgR) occur following traumatic brain injury in the rat

Marklund

Fulp

Shimizu

et al. 2006

Experimental Neurology

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Axons show a poor regenerative capacity following traumatic central nervous system (CNS) injury, partly due to the expression of inhibitors of axonal outgrowth, of which Nogo-A is considered the most important. We evaluated the acute expression of Nogo-A, the Nogo-66 receptor (NgR) and the novel small proline-rich repeat protein 1A (SPRR1A, previously undetected in brain), following experimental lateral fluid percussion (FP) brain injury in rats. Immunofluorescence with antibodies against Nogo-A, NgR and SPRR1A was combined with antibodies against the neuronal markers NeuN and microtubule-associated protein (MAP)-2 and the oligodendrocyte marker RIP, while Western blot analysis was performed for Nogo-A and NgR. Brain injury produced a significant increase in Nogo-A expression in injured cortex, ipsilateral external capsule and reticular thalamus from days 1-7 post-injury (P < 0.05) compared to controls. Increased expression of Nogo-A was observed in both RIP-and NeuN positive (+) cells in the ipsilateral cortex, in NeuN (+) cells in the CA3 region of the hippocampus and reticular thalamus and in RIP (+) cells in white matter tracts. Alterations in NgR expression were not observed following traumatic brain injury (TBI). Brain injury increased the extent of SPRR1A expression in the ipsilateral cortex and the CA3 at all post-injury time-points in NeuN (+) cells. The marked increases in Nogo-A and SPRR1A in several important brain regions suggest that although inhibitors of axonal growth may be upregulated, the injured brain is also capable of expressing proteins promoting axonal outgrowth following TBI. KeywordsNogo-A; Nogo-66 receptor; Small proline-rich repeat protein 1A (SPRR1A); Traumatic brain injury; Oligodendrocytes

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“…Axonal injury is a common finding in TBI and is associated with both morbidity and mortality (Adams et al, 1989;Christman et al, 1994;Maxwell et al, 1997). The original assumption that TBI results in immediate axotomy because of mechanical shearing of the axon describes only a small percentage of the most severely injured fibers (Maxwell et al, 1993(Maxwell et al, , 1997.…”

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Relationship between Flow-Metabolism Uncoupling and Evolving Axonal Injury after Experimental Traumatic Brain Injury

Chen

Richards

Smielewski

et al. 2004

J Cereb Blood Flow Metab

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Summary: Blood flow-metabolism uncoupling is a welldocumented phenomenon after traumatic brain injury, but little is known about the direct consequences for white matter. The aim of this study was to quantitatively assess the topographic interrelationship between local cerebral blood flow (LCBF) and glucose metabolism (LCMRglc) after controlled cortical impact injury and to determine the degree of correspondence with the evolving axonal injury. LCMRglc and LCBF measurements were obtained at 3 hours in the same rat from 18 Ffluorodeoxyglucose and 14 C-iodoantipyrine coregistered autoradiographic images, and compared to the density of damaged axonal profiles in adjacent sections and in an additional group at 24 hours using beta-amyloid precursor protein (ß-APP) immunohistochemistry. LCBF was significantly reduced over the ipsilateral hemisphere by 48 ± 15% compared with shamcontrols, whereas LCMRglc was unaffected, apart from foci of elevated LCMRglc in the contusion margin. Flow-metabolism was uncoupled, indicated by a significant 2-fold elevation in the LCMRglc/LCBF ratio within most ipsilateral structures. There was a significant increase in ß-APP-stained axons from 3 to 24 hours, which was negatively correlated with LCBF and positively correlated with the LCMRglc/LCBF ratio at 3 hours in the cingulum and corpus callosum. Our study indicates a possible dependence of axonal outcome on flow-metabolism in the acute injury stage.

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A Mechanistic Analysis of Nondisruptive Axonal Injury: A Review

Cited by 523 publications

References 94 publications

Modelos experimentales de traumatismo craneoencefálico

Modelos experimentales de traumatismo craneoencefálico

Selective temporal and regional alterations of Nogo-A and small proline-rich repeat protein 1A (SPRR1A) but not Nogo-66 receptor (NgR) occur following traumatic brain injury in the rat

Relationship between Flow-Metabolism Uncoupling and Evolving Axonal Injury after Experimental Traumatic Brain Injury

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