The Controlled Cortical Impact Model of Experimental Brain Trauma: Overview, Research Applications, and Protocol

Osier, Nicole Danielle; Kline, Anthony E.; Dixon, C. Edward

doi:10.1007/978-3-030-16082-1_26

Cited by 6 publications

(10 citation statements)

References 68 publications

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“…The major organs involved in Barth syndrome are the heart, the liver, and skeletal muscle, with minimal involvement of the CNS, resulting in mild learning disabilities and attention deficit as common features (41). The markedly greater learning deficits known to occur in the CCI model (61) suggest that CL oxidation is the major contributor to brain damage. This is further supported by improved neurobehavioral outcomes with the use of inhibitors of CL oxidation after acute CNS insults (16, 51).…”

Section: Discussionmentioning

confidence: 99%

Disentangling oxidation/hydrolysis reactions of brain mitochondrial cardiolipins in pathogenesis of traumatic injury

Chao¹,

Anthonymuthu²,

Kenny³

et al. 2018

JCI Insight

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Section: Discussionmentioning

confidence: 99%

Disentangling oxidation/hydrolysis reactions of brain mitochondrial cardiolipins in pathogenesis of traumatic injury

Chao¹,

Anthonymuthu²,

Kenny³

et al. 2018

JCI Insight

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“…The controlled cortical impact (CCI) was chosen to establish the animal model of TBI as described previously [31,32]. After intraperitoneal injection of pentobarbital, a 5 mm diameter hole was drilled over the right hemisphere bone equidistant between the lambda and bregma.…”

Section: Animal Model Of Controlled Cortical Injurymentioning

confidence: 99%

Epitranscriptomic profiling of N6-methyladenosine-related RNA methylation in rat cerebral cortex following traumatic brain injury

Zhang

et al. 2020

Mol Brain

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Background: N6-methyladenosine (m6A) is the most prevalent post-transcriptional modification of eukaryotic mRNA. It has been reported that there is a stimulus-dependent regulation of m6A in the mammalian central nervous system in response to sensory experience, learning, and injury. The mRNA m6A methylation pattern in rat cortex after traumatic brain injury (TBI) has not been investigated. Results: In this study, we conducted a genome-wide profiling of mRNA m6A methylation in rat cortex via methylated RNA immunoprecipitation sequencing (MeRIP-Seq). After TBI, the expressions of METTL14 and FTO were significantly down-regulated in rat cerebral cortex. Using MeRIP-Seq, we identified a total of 2165 significantly changed peaks, of which 1062 were significantly up-regulated and 1103 peaks were significantly down-regulated. These m6A peaks were located across 1850 genes. The analysis of both m6A peaks and mRNA expression revealed that there were 175 mRNA significantly altered methylation and expression levels after TBI. Moreover, it was found that functional FTO is necessary to repair neurological damage caused by TBI but has no effect on the spatial learning and memory abilities of TBI rats by using FTO inhibitor FB23-2.Conclusion: This study explored the m6A methylation pattern of mRNA after TBI in rat cortex and identified FTO as possible intervention targets in the epigenetic modification of TBI.

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“…An alternative model of focal brain deformation known as the controlled cortical impact (CCI) model of TBI was subsequently developed for use in ferrets (Lighthall, ), and adapted for use in other species including rodents (Dixon, Clifton, Lighthall, Yaghmai, & Hayes, ; Fox, Fan, Levasseur, & Faden, ), pigs (Duhaime et al, ; Manley et al, ), primates (King et al, ), and, more recently, sheep (Dutschke et al, ). As with FPI, CCI requires a craniectomy to gain access to the brain, although instead of a fluid pressure pulse to induce deformation injury, it uses a pneumatic or electromechanically driven metallic piston (Osier and Dixon, ). It typically produces focal injury with neuronal loss, disruption of vasculature, and edema, with more hemorrhage than observed in FPI (Osier and Dixon, ).…”

Section: Focal Brain Deformationmentioning

confidence: 99%

“…As with FPI, CCI requires a craniectomy to gain access to the brain, although instead of a fluid pressure pulse to induce deformation injury, it uses a pneumatic or electromechanically driven metallic piston (Osier and Dixon, ). It typically produces focal injury with neuronal loss, disruption of vasculature, and edema, with more hemorrhage than observed in FPI (Osier and Dixon, ). The severity of injury can be varied by altering the depth of impactor penetration, along with the velocity of the impactor and the dwell time (time of tissue contact).…”

Section: Focal Brain Deformationmentioning

confidence: 99%

“…In large part, this is because rodents offer a low‐cost option with readily available outcome measures and a considerable database of normative data that has been carefully developed and collated over many years. Interested readers can find details of these models, and how they reproduce various aspects of human outcomes after TBI, in some excellent reviews that have recently been published and need not be reiterated here (Bondi et al, ; Cernak, ; Lyeth, ; Osier & Dixon, ). However, rodents were not always the animal species of choice, with several species of larger animals being more commonly used in studies up until the 1980s.…”

Section: Introductionmentioning

confidence: 99%

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Large animal models of traumatic brain injury

Vink

2017

J of Neuroscience Research

111

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Animal models are essential to gain a deeper understanding of the pathophysiology associated with traumatic brain injury (TBI). Rodent models of TBI have proven highly valuable with respect to the information they have provided over the years, particularly when it comes to the molecular understanding of injury mechanisms. However, there has been a failure to translate the successes in therapeutic treatment of TBI in rodents, which many believe may be related to their different brain anatomy compared with humans. Specifically, the rodent lissencephalic brain within its bony skull responds differently to injury than a human gyrencephalic brain, particularly from a biomechanical and physiological perspective. There is now far greater interest in developing more clinically relevant, large animal models of TBI so as to enhance the possibility of successful clinical translation.The current mini-review highlights the differences between lissencephalic and gyrencephalic brains, emphasizing how these differences might impact studies of TBI. Thereafter follows a summary of the different large animal models, with a critical analysis of their strengths and weaknesses. | I N TR ODU C TI ONIt is widely accepted that an understanding of the pathology associated with human traumatic brain injury (TBI) and the development of effective treatment strategies cannot be optimally pursued in a clinical scenario. Indeed, the heterogeneity of injury in clinical TBI is simply too complex to identify independent mechanisms of injury, largely because the primary injury in human TBI is caused in a variety of ways ranging from direct impact of the head to acceleration/deceleration and blast (Gennarelli, 1993). Moreover, this primary mechanical injury initiates a secondary injury cascade that is in large part dependent on the type of primary insult (Blumbergs, Reilly, & Vink, 2008). For example, penetrating focal injuries result in extensive hemorrhage that is not typical of acceleration/deceleration injuries, with this hemorrhage and external access to the brain presenting an entirely different secondary injury cascade with its own peculiar challenges compared with more diffuse injury. Accordingly, experimental models of TBI have been developed to replicate specific aspects of the human condition such that the different factors associated with injury can be individually identified and appropriate targeted interventions developed (Cernak, 2005). And while most models do not replicate all aspects of the human condition, this is a necessary prerequisite given that human injury reflects a complex spectrum of different injury mechanisms. Different animal models allow the differentiation of these injury mechanisms. Only after the differentiation of these neuronal injury mechanisms has been successfully achieved can the complicating effects of extracranial injury, hemorrhagic shock, and clinically realistic treatment and resuscitation strategies be examined in detail.Of the variety of animal species currently being used to model TBI, the r...

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The Controlled Cortical Impact Model of Experimental Brain Trauma: Overview, Research Applications, and Protocol

Cited by 6 publications

References 68 publications

Disentangling oxidation/hydrolysis reactions of brain mitochondrial cardiolipins in pathogenesis of traumatic injury

Disentangling oxidation/hydrolysis reactions of brain mitochondrial cardiolipins in pathogenesis of traumatic injury

Epitranscriptomic profiling of N6-methyladenosine-related RNA methylation in rat cerebral cortex following traumatic brain injury

Large animal models of traumatic brain injury

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