Lateral Fluid Percussion Brain Injury: A 15-Year Review and Evaluation

Abstract

This article comprehensively reviews the lateral fluid percussion (LFP) model of traumatic brain injury (TBI) in small animal species with particular emphasis on its validity, clinical relevance and reliability. The LFP model, initially described in 1989, has become the most extensively utilized animal model of TBI (to date, 232 PubMed citations), producing both focal and diffuse (mixed) brain injury. Despite subtle variations in injury parameters between laboratories, universal findings are evident across studies, including histological, physiological, metabolic, and behavioral changes that serve to increase the reliability of the model. Moreover, demonstrable histological damage and severity-dependent behavioral deficits, which partially recover over time, validate LFP as a clinically-relevant model of human TBI. The LFP model, also has been used extensively to evaluate potential therapeutic interventions, including resuscitation, pharmacologic therapies, transplantation, and other neuroprotective and neuroregenerative strategies. Although a number of positive studies have identified promising therapies for moderate TBI, the predictive validity of the model may be compromised when findings are translated to severely injured patients. Recently, the clinical relevance of LFP has been enhanced by combining the injury with secondary insults, as well as broadening studies to incorporate issues of gender and age to better approximate the range of human TBI within study design. We conclude that the LFP brain injury model is an appropriate tool to study the cellular and mechanistic aspects of human TBI that cannot be addressed in the clinical setting, as well as for the development and characterization of novel therapeutic interventions. Continued translation of pre-clinical findings to human TBI will enhance the predictive validity of the LFP model, and allow novel neuroprotective and neuroregenerative treatment strategies developed in the laboratory to reach the appropriate TBI patients.

Modulation of the cAMP signaling pathway after traumatic brain injury

“…The parasagittal FPI model leads to reproducible histopathology in the brain, similar to the pathology typically seen in TBI patients (Dietrich et al, 1994, Gennarelli, 1994, Keane et al, 2001, Thompson et al, 2005. Accordingly, there are consistent, quantifiable focal and diffuse histopathologies that are all potential therapeutic targets (Dietrich et al, 1994, Bramlett et al, 1997, Ciallella et al, 2002, Grady et al, 2003, Suzuki et al, 2003, Suzuki et al, 2004, Witgen et al, 2005.…”

Modelos experimentales de traumatismo craneoencefálico

“…El daño cerebral traumático se induce liberando un péndulo que impacta una columna de fluido sobre la superficie dural intacta, que ha sido expuesta previamente mediante una pequeña craneotomía 114 . El impacto del fluido sobre la corteza produce un desplazamiento del cerebro que determina fuerzas de tensión en el tejido cerebral, tratán-dose de un modelo de mecánica compleja.…”

“…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%). Por otro lado, el control biomecánico es limitado y complejo de realizar 114 , determinando una variabilidad significativa en el daño producido.…”

Acute cognitive impairment after lateral fluid percussion brain injury recovers by 1 month: Evaluation by conditioned fear response

“…Specifically, lesions of the hippocampus selectively impair contextual conditioned fear [46,66], whereas lesions of the amygdala impair both cued and contextual conditioned fear [66]. Hippocampal damage after lateral FPI includes cell loss, glial activation, electrophysiological dysfunction, and a host of gene expression changes [81]. In this way, anterograde deficits in the acquisition or expression of contextual conditioned fear can be demonstrated within one-week after lateralized brain injury in the rat [2,41].…”

“…Additionally, components of post-concussion syndrome, including impaired affective and emotional function, may result from pathophysiology in the extended limbic system, including the amygdala [61]. Lateral fluid percussion brain injury (FPI) in the rodent reproduces many of the pathological features of human TBI, including neuronal loss, gliosis, metabolic, and ionic perturbations [81], which contribute to an enduring cognitive impairment [67]. However, deficits in amygdala function, giving rise to impaired affect, remain understudied in experimental TBI.…”