Models used in the study of traumatic brain injury

Estrada-Rojo, Francisco; Martínez‐Tapia, Ricardo Jesús; Estrada-Bernal, Francisco; Martínez-Vargas, Marina; Pérez-Arredondo, Adán; Flores-Avalos, Luis; Navarro, Luz

doi:10.1515/revneuro-2017-0028

Cited by 10 publications

(7 citation statements)

References 45 publications

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“…Although some have challenged this idea (Brody et al, 2008;Schwetye et al, 2010), rapid increases in amyloidogenesis have been frequently reported following TBI, regardless of severity (D. H. Smith et al, 1998;Emmerling et al, 2000;X. H. Chen et al, 2004;Abrahamson et al, 2006Abrahamson et al, , 2009Loane et al, 2009;Gatson et al, 2013;Marklund et al, 2014;Estrada-Rojo et al, 2018). Whether amyloidogenesis can result directly from mild neuronal stretch has not been explored.…”

Section: Discussionmentioning

confidence: 99%

Amyloidogenic Processing of Amyloid Precursor Protein Drives Stretch-Induced Disruption of Axonal Transport in hiPSC-Derived Neurons

et al. 2021

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Traumatic brain injury (TBI) results in disrupted brain function following impact from an external force and is a risk factor for sporadic Alzheimer's disease (AD). Although neurologic symptoms triggered by mild traumatic brain injuries (mTBI), the most common form of TBI, typically resolve rapidly, even an isolated mTBI event can increase the risk to develop AD. Aberrant accumulation of amyloid b peptide (Ab), a cleaved fragment of amyloid precursor protein (APP), is a key pathologic outcome designating the progression of AD following mTBI and has also been linked to impaired axonal transport. However, relationships among mTBI, amyloidogenesis, and axonal transport remain unclear, in part because of the dearth of human models to study the neuronal response following mTBI. Here, we implemented a custom-microfabricated device to deform neurons derived from humaninduced pluripotent stem cells, derived from a cognitively unimpaired male individual, to mimic the mild stretch experienced by neurons during mTBI. Although no cell lethality or cytoskeletal disruptions were observed, mild stretch was sufficient to stimulate rapid amyloidogenic processing of APP. This processing led to abrupt cessation of APP axonal transport and progressive formation of aberrant axonal accumulations that contained APP, its processing machinery, and amyloidogenic fragments. Consistent with this sequence of events, stretch-induced defects were abrogated by reducing amyloidogenesis either pharmacologically or genetically. In sum, we have uncovered a novel and manipulable stretch-induced amyloidogenic pathway directly responsible for APP axonal transport dysregulation. Our findings may help to understand and ultimately mitigate the risk of developing AD following mTBI.

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Section: Discussionmentioning

confidence: 99%

Amyloidogenic Processing of Amyloid Precursor Protein Drives Stretch-Induced Disruption of Axonal Transport in hiPSC-Derived Neurons

et al. 2021

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“…Models of acute hematoma show intracranial hematoma due to tearing or rupture of veins. Animal models of TBI provide invaluable information on the pathological effects of brain injury particularly biomarker discovery and preclinical screening of drugs (Estrada-Rojo and others 2018). However, translation of research findings from animal models of TBI into human patients remain extremely difficult due to immunological, anatomical, and functional differences between the CNS of human and small animals (Sorby-Adams and others 2018).…”

Section: Animal Models Of Brain Injurymentioning

confidence: 99%

Brain Injury–Mediated Neuroinflammatory Response and Alzheimer’s Disease

et al. 2019

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Traumatic brain injury (TBI) is a major health problem in the United States, which affects about 1.7 million people each year. Glial cells, T-cells, and mast cells perform specific protective functions in different regions of the brain for the recovery of cognitive and motor functions after central nervous system (CNS) injuries including TBI. Chronic neuroinflammatory responses resulting in neuronal death and the accompanying stress following brain injury predisposes or accelerates the onset and progression of Alzheimer’s disease (AD) in high-risk individuals. About 5.7 million Americans are currently living with AD. Immediately following brain injury, mast cells respond by releasing prestored and preactivated mediators and recruit immune cells to the CNS. Blood-brain barrier (BBB), tight junction and adherens junction proteins, neurovascular and gliovascular microstructural rearrangements, and dysfunction associated with increased trafficking of inflammatory mediators and inflammatory cells from the periphery across the BBB leads to increase in the chronic neuroinflammatory reactions following brain injury. In this review, we advance the hypothesis that neuroinflammatory responses resulting from mast cell activation along with the accompanying risk factors such as age, gender, food habits, emotional status, stress, allergic tendency, chronic inflammatory diseases, and certain drugs can accelerate brain injury-associated neuroinflammation, neurodegeneration, and AD pathogenesis.

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“…After 24 h, all traumatized subjects showed a sudden drop in body weight and food intake, particularly noticeable in the rats subjected to TBI during the light cycle phase, followed by a rapid rebound three days later. However, neither rhTrx1 nor minocycline was able to alter this metabolic response, which might be attributed to the model utilized (mCCI), which despite its mildness, has the features of a mechanical and dynamic animal model whose influence is direct and enters the brain (Estrada‐Rojo et al., 2018a). Our research group previously found that recovery from TBI in a weight drop model in rats is improved if injury occurs during the dark phase of the cycle (Martinez‐Vargas et al., 2006), resulting in less body weight loss, and greater food intake when the impact occurs at 01:00 h rather than 13:00 h—suggesting that neuroprotection responses may have a diurnal variation.…”

Section: Discussionmentioning

confidence: 99%

“…However, Krishna et al. (2019), employing a fluid percussion injury model with similar features to CCl (Estrada‐Rojo et al., 2018a), found no significant changes in average daily food intake or decrease in body weight among the different groups of rats during 2 weeks of observation (Krishna et al., 2019).…”

Section: Discussionmentioning

confidence: 99%

The effect of thioredoxin‐1 in a rat model of traumatic brain injury depending on diurnal variation

Noriega‐Navarro,

Martínez‐Tapia,

González‐Rivera

et al. 2023

Brain and Behavior

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Introduction Traumatic brain injury (TBI) is a public health concern with limited treatment options because it causes a cascade of side effects that are the leading cause of hospital death. Thioredoxin is an enzyme with neuroprotective properties such as antioxidant, antiapoptotic, immune response modulator, and neurogenic, among others; it has been considered a therapeutic target for treating many disorders. Methods The controlled cortical impact (CCI) model was used to assess the effect of recombinant human thioredoxin 1 (rhTrx1) (1 μg/2 μL, intracortical) on rats subjected to TBI at two different times of the light‐dark cycle (01:00 and 13:00 h). We analyzed the food intake, body weight loss, motor coordination, pain perception, and histology in specific hippocampus (CA1, CA2, CA3, and Dental Gyrus) and striatum (caudate‐putamen) areas. Results Body weight loss, reduced food intake, spontaneous pain, motor impairment, and neuronal damage in specific hippocampus and striatum regions are more evident in rats subjected to TBI in the light phase than in the dark phase of the cycle and in groups that did not receive rhTrx1 or minocycline (as positive control). Three days after TBI, there is a recovery in body weight, food intake, motor impairment, and pain, which is more pronounced in the rats subjected to TBI at the dark phase of the cycle and those that received rhTrx1 or minocycline. Conclusions Knowing the time of day a TBI occurs in connection to the neuroprotective mechanisms of the immune response in diurnal variation and the usage of the Trx1 protein might have a beneficial therapeutic impact in promoting quick recovery after a TBI.

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Models used in the study of traumatic brain injury

Cited by 10 publications

References 45 publications

Amyloidogenic Processing of Amyloid Precursor Protein Drives Stretch-Induced Disruption of Axonal Transport in hiPSC-Derived Neurons

Amyloidogenic Processing of Amyloid Precursor Protein Drives Stretch-Induced Disruption of Axonal Transport in hiPSC-Derived Neurons

Brain Injury–Mediated Neuroinflammatory Response and Alzheimer’s Disease

The effect of thioredoxin‐1 in a rat model of traumatic brain injury depending on diurnal variation

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