Adaptation of the Fluid Percussion Injury Model to the Mouse

Abstract

Fluid percussion injury (FPI) is a well-characterized experimental model of traumatic brain injury (TBI) in the rat. Many pathophysiologic consequences and mechanisms of recovery after TBI rely on neurochemical pathways that can be examined in genetically altered mice. Therefore, FPI applied to mice may be a useful experimental tool to investigate TBI at the molecular level. In the present study, we establish FPI as a viable model of TBI in the mouse by characterizing acute neurological, histopathological, and behavioral changes. Right-sided parasagittal FPI or sham treatment was administered in male C57BL/6 mice. Acute neurological evaluation revealed righting reflexes in the injured animals (p < 0.001). Deficits in spatial learning and memory were observed in the Morris water maze (MWM) 5 and 6 days after injury. A novel MWM data analysis protocol is described. The injured group (n = 18) demonstrated impaired performance in the MWM during acquisition (p < 0.05) and probe trials (p < 0.025) compared to sham animals (n = 16). At 7 days postinjury, glial fibrillary acidic protein immunohistochemistry revealed intense cortical, callosal, and hippocampal gliosis. The modified Gallyas silver degeneration stain consistently labeled cell bodies and terminals throughout the ipsilateral cortex, axons in the gray matter-white matter interface above the corpus callosum and within the corpus callosum bilaterally, and terminals and fibers in the thalamus bilaterally. Additionally, the mouse FPI model described is immediately employable in labs already using the FPI rat model with no modifications to a pre-existing FPI apparatus.

Erythropoietin regulates immune/inflammatory reaction and improves neurological function outcomes in traumatic brain injury

“…When anesthesia dissipated, mice were subjected to experimental FPI at a pressure of 2.0 atmosphere (atm). Mice were sterilized and sutured after their vital signs were stable and then returned to the home cage (Carbonell, Maris, McCall, & Grady, 1998). …”

Modelos experimentales de traumatismo craneoencefálico

“…El principal hallazgo neuropatológico observado consiste en una contusión cortical a nivel del sitio del impacto en la interfase entre sustancia gris y blanca, que llegará a convertirse en una cavidad necrótica pasadas unas semanas del traumatismo 28, 44 . Además se observan hemorragias petequiales en el parénquima cerebral (que pueden variar desde pequeños focos hemorrágicos dispersos a áreas hemorrágicas confluentes), lesión axonal difusa bilateral 17,18 , hemorragia subaracnoidea y muerte celular a nivel de la corteza, hipocampo y tálamo ipsilateral 17,18,27,28,50,99. Las principales ventajas de este modelo son su alta reproducibilidad y la capacidad de producir un daño cerebral de diferente grado de severidad según la intensidad del trauma 30,31 . Además puede emplearse con ratones, permitiendo la investigación en animales knockouts o con hiper-expresión de un gen particular 17 .…”

“…Además se observan hemorragias petequiales en el parénquima cerebral (que pueden variar desde pequeños focos hemorrágicos dispersos a áreas hemorrágicas confluentes), lesión axonal difusa bilateral 17,18 , hemorragia subaracnoidea y muerte celular a nivel de la corteza, hipocampo y tálamo ipsilateral 17,18,27,28,50,99. Las principales ventajas de este modelo son su alta reproducibilidad y la capacidad de producir un daño cerebral de diferente grado de severidad según la intensidad del trauma 30,31 . Además puede emplearse con ratones, permitiendo la investigación en animales knockouts o con hiper-expresión de un gen particular 17 . La principal desventaja del modelo LFP y que limita su utilidad, es que al aumentar la intensidad del impacto éste afecta de forma desproporcionada el tronco cerebral, lo que puede conducir al desarrollo de edema pulmonar neurogénico y a una elevada mortalidad (50%).…”

Alterations in Mammalian Target of Rapamycin Signaling Pathways after Traumatic Brain Injury

“…Knockdown of the NMDA-type glutamate receptor 1 in a mere 6% to 7% of CA1 neurons in the hippocampus is enough to significantly impair memory formation (Cheli et al, 2006). The FPI model, without any accompanying hypoxia, does not result in substantial neuronal loss throughout the hippocampus with the exception of the CA3 and hilar subregions, but does result in significant hippocampal-dependent memory impairments (Lyeth et al, 1990;Carbonell et al, 1998;Grady et al, 2003). Accordingly, hippocampal LTP is impaired and subtle structural damage is seen in the hippocampus after TBI (Sanders et al, 2000;Golarai et al, 2001;Scheff et al, 2005).…”