A murine model of mild traumatic brain injury exhibiting cognitive and motor deficits

Yang, Sung H.; Gustafson, Josh; Gangidine, Matt; Stepien, David M.; Schuster, Rebecca; Pritts, Timothy A.; Goodman, Michael D.; Remick, Daniel G.; Lentsch, Alex B.

doi:10.1016/j.jss.2013.03.075

Cited by 97 publications

(85 citation statements)

References 28 publications

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“…85 Furthermore, prior studies have shown IL-6, a pro-inflammatory cytokine, to be an independent predictor of mTBI. 86,87 Interestingly, the findings of a study that evaluated inflammatory markers in 16 pediatric patients demonstrated higher concentrations of IL-6 in patients with mTBI relative to controls without injury, (p < 0.00). 88 Finally, these investigations highlighted novel inflammatory markers that can, to some extent, uniquely classify mTBI in human patients, thereby translating theory into clinical practice.…”

Section: Studies Of Tbi and Inflammatory Responsesmentioning

confidence: 99%

Effects of concussion on the blood–brain barrier in humans and rodents

Sahyouni

Gutierrez

Gold

et al. 2017

Journal of Concussion

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Traumatic brain injury and the long-term consequences of repeated concussions constitute mounting concerns in the United States, with 5.3 million individuals living with a traumatic brain injury-related disability. Attempts to understand mechanisms and possible therapeutic approaches to alleviate the consequences of repeat mild concussions or traumatic brain injury on cerebral vasculature depend on several aspects of the trauma, including: (1) the physical characteristics of trauma or insult that result in damage; (2) the time ''window'' after trauma in which neuropathological features develop; (3) methods to detect possible breakdown of the blood-brain barrier; and (4) understanding different consequences of a single concussion as compared with multiple concussions. We review the literature to summarize the current understanding of blood-brain barrier and endothelial cell changes post-neurotrauma in concussions and mild traumatic brain injury. Attention is focused on concussion and traumatic brain injury in humans, with a goal of pointing out the gaps in our knowledge and how studies of rodent model systems of concussion may help in filling these gaps. Specifically, we focus on disruptions that concussion causes to the blood-brain barrier and its multifaceted consequences. Importantly, the magnitude of post-concussion blood-brain barrier dysfunction may influence the time course and extent of neuronal recovery; hence, we include in this review comparisons of more severe traumatic brain injury to concussion where appropriate. Finally, we address the important, and still unresolved, issue of how best to detect possible breakdown in the blood-brain barrier following neurotrauma by exploring intravascular tracer injection in animal models to examine leakage into the brain parenchyma.

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Section: Studies Of Tbi and Inflammatory Responsesmentioning

confidence: 99%

Effects of concussion on the blood–brain barrier in humans and rodents

Sahyouni

Gutierrez

Gold

et al. 2017

Journal of Concussion

View full text Add to dashboard Cite

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“…12,20,29,[35][36][37][38][39][135][136][137][138][139] These models avoid the severe brain injury of open-skull models and the contributions of injury to other parts of the head or body that occur in a whole head or whole body blast model. The severity of the TBI with both the weight-drop and impactor approaches can be adjusted by changing the height of the weight drop or the impactor force, and the concussive impact can be delivered to different parts of the cranium to explore regional differences in TBI effects.…”

Section: Comparison With Blast Models In Rodentsmentioning

confidence: 99%

“…26,[35][36][37][38][39] The head, however, is typically not restrained in weight-drop, piston impact, and blast models, and its rapid displacement means that head acceleration contributes to the brain injury. Although head impact by a blow or blast together with head movement is true to many real world concussive events, their combined contribution makes it more difficult to ascertain the biomechanical basis of a specific neural injury in an animal model.…”

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confidence: 99%

A Novel Closed-Head Model of Mild Traumatic Brain Injury Using Focal Primary Overpressure Blast to the Cranium in Mice

Guley

Rogers

Mar

et al. 2016

Journal of Neurotrauma

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Mild traumatic brain injury (TBI) from focal head impact is the most common form of TBI in humans. Animal models, however, typically use direct impact to the exposed dura or skull, or blast to the entire head. We present a detailed characterization of a novel overpressure blast system to create focal closed-head mild TBI in mice. A high-pressure air pulse limited to a 7.5 mm diameter area on the left side of the head overlying the forebrain is delivered to anesthetized mice. The mouse eyes and ears are shielded, and its head and body are cushioned to minimize movement. This approach creates mild TBI by a pressure wave that acts on the brain, with minimal accompanying head acceleration-deceleration. A single 20-psi blast yields no functional deficits or brain injury, while a single 25-40 psi blast yields only slight motor deficits and brain damage. By contrast, a single 50-60 psi blast produces significant visual, motor, and neuropsychiatric impairments and axonal damage and microglial activation in major fiber tracts, but no contusive brain injury. This model thus reproduces the widespread axonal injury and functional impairments characteristic of closed-head mild TBI, without the complications of systemic or ocular blast effects or head acceleration that typically occur in other blast or impact models of closed-skull mild TBI. Accordingly, our model provides a simple way to examine the biomechanics, pathophysiology, and functional deficits that result from TBI and can serve as a reliable platform for testing therapies that reduce brain pathology and deficits.

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“…Targets identified are typically validated using multiplex arrays or reverse phase protein microarrays. 145,146 However, despite the rapidly expanding toolbox for identifying new biomarkers, a massive disconnect still exists between the laboratory and the clinic, partly due to the underreporting of sports-related injuries.…”

Section: Biomarker Discovery: Current Prospects and Challengesmentioning

confidence: 99%

Sports-related brain injuries: connecting pathology to diagnosis

Pan¹,

Connolly²,

Dangelmajer³

et al. 2016

FOC

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Neurosurg Focus 40 (4):E14, 2016M any sports-related brain injuries involve mild traumatic brain injuries (mTBIs), which result from physical blows to the head sustained over a period of time. Sports associated with an increased risk of head injury include American football, ice hockey, soccer, rugby, the martial arts, boxing, and bicycling. 21,90 These injuries are often unrecognized, undiagnosed, or underreported, which reflects the fact that this is a growing medical concern, often labeled a "silent epidemic." 8,66 Chronic exposure to mild brain injuries can result in long-term neurological consequences and represents a spectrum of disorders. The most remarkable outcome of mTBI is termed chronic traumatic encephalopathy (CTE), a clinical syndrome that is associated with neurodegeneration and behavioral, cognitive, and/or motor deficits. Although this disease has distinct pathological features, CTE is considered a diagnosis of exclusion because only postmortem biopsies can confirm the diagnosis. Therefore, new diagnostic methods need to be developed to: 1) inform patients of a definitive diagnosis, 2) better understand the epidemiology and risk factors of the disease, and 3) implement intervention programs to prevent any potential long-term complications. This review examines how understanding the pathology and molecular changes associated with repeated head trauma can lead to the discovery of novel imaging techniques and biomarkers. Mild Traumatic Brain Injury and CTEChronic traumatic encephalopathy has evolved from the so-called punch-drunk syndrome, which was used to describe a distinct neuropsychiatric condition that seemed to affect boxers, eventually becoming known as dementia pugilistica during the 1920s and 1930s. Symptoms such ABBrEvIATIoNs AD = Alzheimer's disease; APOE = apolipoprotein E; ASL = arterial spin labeling; BBB = blood-brain barrier; BOLD = blood oxygen level-dependent; CA = cornu ammonis; CTE = chronic traumatic encephalopathy; DTI = diffusion tensor imaging; FA = fractional anisotropy; fMRI = functional MRI; GFAP = glial fibrillary acidic protein; GRE = gradient recall echo; miRNA = microRNA; MRS = MR spectroscopy; mTBI = mild traumatic brain injury; NFL = National Football League; NFT = neurofibrillary tangle; NINDS = National Institute of Neurological Disorders and Stroke; NSE = neuron-specific enolase; p-tau = phosphorylated tau; SWI = susceptibility-weighted imaging; TDP-43 = TAR DNA-binding protein 43;18 F-FDDNP = 2-(1-{6- [(2-[fluorine-18] Brain injuries are becoming increasingly common in athletes and represent an important diagnostic challenge. Early detection and management of brain injuries in sports are of utmost importance in preventing chronic neurological and psychiatric decline. These types of injuries incurred during sports are referred to as mild traumatic brain injuries, which represent a heterogeneous spectrum of disease. The most dramatic manifestation of chronic mild traumatic brain injuries is termed chronic traumatic encephalopathy, which is associated with profo...

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A murine model of mild traumatic brain injury exhibiting cognitive and motor deficits

Cited by 97 publications

References 28 publications

Effects of concussion on the blood–brain barrier in humans and rodents

Effects of concussion on the blood–brain barrier in humans and rodents

A Novel Closed-Head Model of Mild Traumatic Brain Injury Using Focal Primary Overpressure Blast to the Cranium in Mice

Sports-related brain injuries: connecting pathology to diagnosis

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