Upregulation of Amyloid Precursor Protein Messenger RNA in Response to Traumatic Brain Injury: An Ovine Head Impact Model

Heuvel, Corinna van den; Blumbergs, Peter; Finnie, JW; Manavis, Jim; Jones, Nigel R.; Reilly, Peter; Pereira, Rosemarie A.

doi:10.1006/exnr.1999.7150

Cited by 116 publications

(74 citation statements)

References 62 publications

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“…Thus, direct cortical impact has been modeled in swine [17,18] , unrestrained head impact in swine [19] and sheep [20,21] , and fluid percussion in swine [22] . Because of their appropriate brain size and shape, pure inertial injury was first modeled in primates [14,23] and later adapted to swine [24] .…”

Section: Mechanismmentioning

confidence: 99%

Large Animal Models of Traumatic Injury to the Immature Brain

Duhaime

2006

Dev Neurosci

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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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Section: Mechanismmentioning

confidence: 99%

Large Animal Models of Traumatic Injury to the Immature Brain

Duhaime

2006

Dev Neurosci

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“…It was previously reported that APP mRNA and protein levels were increased in neurons after TBI ( Van den Heuvel et al, 1999;Ciallella et al, 2002). Furthermore, expression of APP was increased in neurons after ischemia and axonal injury (Stephenson et al, 1992;Xie et al, 2003).…”

Section: Discussionmentioning

confidence: 89%

“…Recent evidence suggests that APP, a ubiquitously expressed, highly conserved integral membrane glycoprotein, is not only a sensitive marker of axonal injury (Gentleman et al, 1993;Blumbergs et al, 1995), but may also have an important functional role following TBI. APP is upregulated acutely in injured neurons and reactive astrocytes following TBI (Pierce et al, 1996;Van den Heuvel et al, 1999), and this upregulation has been associated with increase hippocampal cell death (Murakami et al, 1998). Although the mechanisms leading to cell death are unknown, as the precursor to the neurotoxic A protein, the conversion of APP to A may have detrimental effects including an increased risk for development of Alzheimer's disease (Chen et al, 2004).…”

Section: Discussionmentioning

confidence: 99%

Expression and Cerebral Function of Amyloid Precursor Protein After Rat Traumatic Brain Injury

Itoh¹,

Imano²,

Nishida³

et al. 2011

Alzheimer's Disease Pathogenesis-Core Concepts, Shifting Paradigms and Therapeutic Targets

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“…1-3) is the most sensitive marker of AI, 105 identifying axonal swellings within 30 minutes postimpact and with minimal background interference because uninjured axons do not stain with this technique. 33,36,64,114,115 But APP immunoreactive axons can still be identified many months after head injury. 17 The total burden of AI in a given brain has been underestimated using traditional, less sensitive staining methods such as hematoxylin and eosin and silver impregnation.…”

Section: Traumatic Aimentioning

confidence: 99%

Traumatic Brain Injury

2002

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Abstract. Animal models have played a critical role in elucidating the complex pathogenesis of traumatic brain injury, the major cause of death and disability in young adults in Western countries. This review discusses how different types of animal models are useful for the study of neuropathologic processes in traumatic, blunt, nonmissile head injury.Key words: Animal models; neuropathology; pathogenesis; traumatic brain injury.There are two main reasons for conducting research on traumatic, blunt, nonmissile brain injury. First, traumatic brain injury (TBI) is the leading cause of death and severe disability in people under 45 years of age in Western industrialized countries, affecting the young and adults in the most productive years of their lives and predominantly caused by motor vehicle accidents. For every fatality, there are many survivors with severe brain damage and many more with moderate or mild injury. 30,51,63 Although TBI is a problem of major medical and socioeconomic significance, its pathogenesis is incompletely understood, and it is often difficult to reconstruct the events leading to the primary and secondary lesions of varying severity and regional distribution that constitute TBI. 11,50 In contrast, the mechanical input in animal models is quantifiable and subject to manipulation, and head injuries are produced under controlled experimental conditions. Second, although a host of potential neuroprotective agents have been studied, the few that have shown promise under experimental conditions have failed to provide consistent and significant improvement in human clinical trials. 14,16,29,108 Testing the efficacy of new drugs in animal models will therefore continue to be an essential precursor to their use in humans.TBI is also frequently encountered in veterinary practice as a result of automobile accidents, falls, assaults, bites, and crushing injuries. 19,110 But head injury in animals has generally received scant attention in the veterinary literature, and most of our knowledge is derived from their use as experimental models of human TBI. 34 This review highlights the contribution of different types of animal models to our understanding of the neuropathology of head injury. Types of Animal ModelsTBI may be produced by the head impacting or coming into contact with an object (contact phenomena) or acceleration/deceleration forces producing vigorous movement of the brain (acceleration/deceleration or inertial phenomena), or varying combinations of these mechanical forces. 11,34,50,51,91 In most models, the mechanical input is controlled and results in injury that is reproducible, quantifiable, and clinically relevant. No single animal model can reliably replicate the full spectrum of human TBI. 40,42,67,68,87,88,90 Animal models of TBI can be broadly classified as • impact acceleration models • inertial (nonimpact) acceleration models • direct brain deformation models.Impact acceleration models involve direct head impacts using a piston, humane stunner or captive bolt pistol, calibrated p...

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Upregulation of Amyloid Precursor Protein Messenger RNA in Response to Traumatic Brain Injury: An Ovine Head Impact Model

Cited by 116 publications

References 62 publications

Large Animal Models of Traumatic Injury to the Immature Brain

Large Animal Models of Traumatic Injury to the Immature Brain

Expression and Cerebral Function of Amyloid Precursor Protein After Rat Traumatic Brain Injury

Traumatic Brain Injury

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