Large Animal Models of Traumatic Injury to the Immature Brain

Pediatric Neurosurgery, Children's Hospital at Dartmouth, Dartmouth Hitchcock Medical Center, Lebanon, NH 03756, USA.
Developmental Neuroscience (Impact Factor: 2.7). 02/2006; 28(4-5):380-7. DOI: 10.1159/000094164
Source: PubMed


Large animal models have been used much less frequently than rodent models to study traumatic brain injury. However, large animal models offer distinct advantages in replicating specific mechanisms, morphology and maturational stages relevant to age-dependent injury responses. This paper reviews how each of these features is relevant in matching a model to a particular scientific question and discusses various scaling strategies, advantages and disadvantages of large animal models for studying traumatic brain injury in infants and children. Progress to date and future directions are outlined.

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    • "In the following sections, we briefly summarize the most commonly used and established experimental models of TBI (Table 1). Several excellent reviews provide a more detailed overview of the wide variety of in vivo animal models of TBI (Lighthall et al., 1989; Povlishock et al., 1994; Finnie, 2001; Cenci et al., 2002; Cernak, 2005; Duhaime, 2006; McCabe et al., 2010; Frink et al., 2011; Marklund and Hillered, 2011; O'Connor et al., 2011; Xiong et al., 2013). "
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    ABSTRACT: Traumatic brain injury (TBI) is a major worldwide healthcare problem. Despite promising outcomes from many preclinical studies, the failure of several clinical studies to identify effective therapeutic and pharmacological approaches for TBI suggests that methods to improve the translational potential of preclinical studies are highly desirable. Rodent models of TBI are increasingly in demand for preclinical research, particularly for closed head injury (CHI), which mimics the most common type of TBI observed clinically. Although seemingly simple to establish, CHI models are particularly prone to experimental variability. Promisingly, bioengineering-oriented research has advanced our understanding of the nature of the mechanical forces and resulting head and brain motion during TBI. However, many neuroscience-oriented laboratories lack guidance with respect to fundamental biomechanical principles of TBI. Here, we review key historical and current literature that is relevant to the investigation of TBI from clinical, physiological and biomechanical perspectives, and comment on how the current challenges associated with rodent TBI models, particularly those involving CHI, could be improved.
    Disease Models and Mechanisms 09/2013; 6(6). DOI:10.1242/dmm.011320 · 4.97 Impact Factor
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    • "This animal model has three major advantages over rodents when studying lipid metabolism. First, brain anatomy and morphology and the timing of the brain growth spurt in pigs and humans are similar (Pond et al., 2000; Duhaime, 2006). "
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    ABSTRACT: Studies suggested that in human adults, linoleic acid (LA) inhibits the biosynthesis of n-3 long-chain polyunsaturated fatty acids (LC-PUFA), but their effects in growing subjects are largely unknown. We used growing pigs as a model to investigate whether high LA intake affects the conversion of n-3 LC-PUFA by determining fatty acid composition and mRNA levels of Δ5- and Δ6 desaturase and elongase 2 and -5 in liver and brain. In a 2 × 2 factorial arrangement, 32 gilts from eight litters were assigned to one of the four dietary treatments, varying in LA and α-linolenic acid (ALA) intakes. Low ALA and LA intakes were 0.15 and 1.31, and high ALA and LA intakes were 1.48 and 2.65 g/kg BW0.75 per day, respectively. LA intake increased arachidonic acid (ARA) in liver. ALA intake increased eicosapentaenoic acid (EPA) concentrations, but decreased docosahexaenoic acid (DHA) (all P < 0.01) in liver. Competition between the n-3 and n-6 LC-PUFA biosynthetic pathways was evidenced by reductions of ARA (>40%) at high ALA intakes. Concentration of EPA (>35%) and DHA (>20%) was decreased by high LA intake (all P < 0.001). Liver mRNA levels of Δ5- and Δ6 desaturase were increased by LA, and that of elongase 2 by both ALA and LA intakes. In contrast, brain DHA was virtually unaffected by dietary LA and ALA. Generally, dietary LA inhibited the biosynthesis of n-3 LC-PUFA in liver. ALA strongly affects the conversion of both hepatic n-3 and n-6 LC-PUFA. DHA levels in brain were irresponsive to these diets. Apart from Δ6 desaturase, elongase 2 may be a rate-limiting enzyme in the formation of DHA.
    animal 02/2012; 6(2):262-70. DOI:10.1017/S1751731111001479 · 1.84 Impact Factor
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    • "Generally, animals can be divided into small and large species, although this is a somewhat arbitrary division. Both groups have advantages and disadvantages (Duhaime, 2006) and it is therefore not possible to prefer one species over the others. Larger brains usually bear more anatomic similarity to the human brain than smaller brains, for instance with regard to gyration. "
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    ABSTRACT: Cerebral arterial gas embolism is a dreaded complication of diving and invasive medical procedures. Many different animal models have been used in research on cerebral arterial gas embolism. This review provides an overview of the most important characteristics of these animal models. The properties discussed are species, cerebrovascular anatomy, method of air embolization, amount of air, bubble size, outcome parameters, anesthesia, blood glucose, body temperature and blood pressure.
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