The neurophysiology of concussion

Shaw, N.A.

doi:10.1016/s0301-0082(02)00018-7

Cited by 309 publications

(237 citation statements)

References 266 publications

Supporting

Mentioning

223

Contrasting

Unclassified

Order By: Relevance

“…4,5 We found that CHI induced phosphorylation of Akt and mTOR and their direct downstream substrates FOXO1 and S6RP, respectively, in cortical and hippocampal brain homogenates. Expression of p-S6RP was upregulated in hippocampal Iba-1-reactive microglia and GFAPreactive astrocytes and was detected in neurons in both brain regions.…”

Section: Discussionmentioning

confidence: 85%

“…3,4 No specific therapy exists to treat or prevent neurologic sequelae of concussion, in part because of incomplete understanding of the specific mechanisms that lead to neurologic dysfunction. 4,5 Akt (protein kinase B) and mammalian target of rapamycin (mTOR) are protein kinases involved in translation, transcription, metabolism, and other cellular homeostatic functions. 6 mTOR exists in two distinct multi-protein complexes, mTOR complex 1 (mTORC1; inhibited by rapamycin) and mTORC2 (rapamycin insensitive).…”

Section: Introductionmentioning

confidence: 99%

See 1 more Smart Citation

Role of Akt and Mammalian Target of Rapamycin in Functional Outcome after Concussive Brain Injury in Mice

Zhu

Park

Golinski

et al. 2014

J Cereb Blood Flow Metab

View full text Add to dashboard Cite

Akt (protein kinase B) and mammalian target of rapamycin (mTOR) have been implicated in the pathogenesis of cell death and cognitive outcome after cerebral contusion in mice; however, a role for Akt/mTOR in concussive brain injury has not been well characterized. In a mouse closed head injury (CHI) concussion traumatic brain injury (TBI) model, phosphorylation of Akt (p-Akt), mTOR (p-mTOR), and S6RP (p-S6RP) was increased by 24 hours in cortical and hippocampal brain homogenates (Po0.05 versus sham for each), and p-S6RP was robustly induced in IBA-1 þ microglia and glial fibrillary acidic protein-positive (GFAP þ ) astrocytes. Pretreatment with inhibitors of Akt or mTOR individually by the intracerebroventricular route reduced phosphorylation of their respective direct substrates FOXO1 (Po0.05) or S6RP (Po0.05) after CHI, confirming the activity of inhibitors. Rapamycin pretreatment significantly worsened hidden platform (Po0.01) and probe trial (Po0.05) performance in CHI mice. Intracerebroventricular administration of necrostatin-1 (Nec-1) before CHI increased hippocampal Akt and S6RP phosphorylation and improved place learning (probe trials, Po0.001 versus vehicle), whereas co-administration of rapamycin or Akt inhibitor with Nec-1 eliminated improved probe trial performance. These data suggest a beneficial role for Akt/mTOR signaling after concussion TBI independent of cell death that may contribute to improved outcome by Nec-1.

show abstract

Section: Discussionmentioning

confidence: 85%

Section: Introductionmentioning

confidence: 99%

Role of Akt and Mammalian Target of Rapamycin in Functional Outcome after Concussive Brain Injury in Mice

Zhu

Park

Golinski

et al. 2014

J Cereb Blood Flow Metab

View full text Add to dashboard Cite

show abstract

“…In humans, or other animals with larger brains and rigid skulls, the prevailing mechanism for concussion is believed to be angular acceleration that leads to deformation of the brain through shearing forces. 26 In mice and rats, the small size of the brain precludes the attainment of large deformations by acceleration of the skull. Accordingly, concussions in the weight-drop model most likely arise from brain deformation resulting from compression of the skull.…”

Section: Discussionmentioning

confidence: 99%

Multiple Episodes of Mild Traumatic Brain Injury Result in Impaired Cognitive Performance in Mice

Creeley¹,

Wozniak²,

Bayly³

et al. 2004

Acad Emergency Med

View full text Add to dashboard Cite

Objectives: Results from recent studies on animal models of concussion suggest that multiple, rather than single, episodes of mild traumatic brain injury result in impaired cognitive performance in mice. The objective of the present study was to administer multiple impacts to the heads of mice while directly measuring the force of the impacts to determine how these parameters are related to transient loss of consciousness, cognitive deficits, and potential neuropathologic effects. Methods: Seven-week-old male C57BL/6 mice were randomly assigned to experimental conditions involving three impacts (weight-drop method) to the head to induce mild traumatic brain injury or to sham control procedures. Some impacted (n ¼ 10) and sham control (n ¼ 10) mice were evaluated behaviorally and tested for spatial learning using the Morris water maze (MWM), whereas other impacted (n ¼ 10) and sham control (n ¼ 5) mice were used for histopathologic analysis. Results: The mean (6SD) force of impact was 19 (63.5) N. Impacted mice took longer to regain consciousness compared with sham control mice (p \ 0.0005). Behavioral test results showed that the groups did not differ on activity or sensorimotor tests or during cued trials in the MWM. Impacted mice exhibited impaired spatial learning performance during place trials in the MWM (p \ 0.05). Silver staining revealed a contra-coup type of injury involving ventral brain structures in contact with or in close proximity to the skull. Conclusions: This multiple-impact model, delivered within a specifiable force range, results in transient, reversible loss of consciousness, a contra-coup brain injury, and cognitive impairment. Key words: traumatic brain injury; concussion; memory; cognition; mice. ACADEMIC EMERGENCY MED-ICINE 2004; 11:809-819. It is not clear whether mild traumatic brain injury (TBI) causes demonstrable long-term cognitive impairment in humans. A number of earlier epidemiologic studies suggest that this may be the case, but the use of retrospective designs, lack of appropriate control groups, and an inability to correct for several confounding factors did not allow for a straightforward interpretation of the results. [1][2][3][4] More recently, a number of studies of athletes who have experienced a sports-related concussion suggest that symptomatology and cognitive impairment can last for one week 5 and, in some cases, up to three months. 6 Animal models have been used to study the behavioral and neuropathologic sequelae associated with TBI. [7][8][9][10] In three of these studies, in which slightly different murine models of mild TBI were used, the results suggested that mild single impacts did not produce discernible learning/memory deficits when behavioral testing was conducted more than three days after impact. [8][9][10] In contrast, multiple mild impacts have usually been found to produce significant effects on behavior, but the nature of these changes has been inconsistent across studies. For example, DeFord et al. 10 reported that multiple mild impacts ...

show abstract

“…The universality of concussions is that the stunned, motorically wobbly appearance commonly observed in an athlete, particularly a boxer who has been concussed, is replicated with animal models (Shaw, 2002). Survivability across mammalian species following concussion is testament to the fact that most concussions are but transient disruptions in normal brain function allowing the animal (including humans) to recover quickly and fully return to pre-injury abilities and activities.…”

Section: Evolutionary Aspects Of Injurymentioning

confidence: 99%

Neuropsychology and clinical neuroscience of persistent post-concussive syndrome

Bigler

2007

J Int Neuropsychol Soc

359

248

View full text Add to dashboard Cite

On the mild end of the acquired brain injury spectrum, the terms concussion and mild traumatic brain injury (mTBI) have been used interchangeably, where persistent post-concussive syndrome (PPCS) has been a label given when symptoms persist for more than three months post-concussion. Whereas a brief history of concussion research is overviewed, the focus of this review is on the current status of PPCS as a clinical entity from the perspective of recent advances in the biomechanical modeling of concussion in human and animal studies, particularly directed at a better understanding of the neuropathology associated with concussion. These studies implicate common regions of injury, including the upper brainstem, base of the frontal lobe, hypothalamic-pituitary axis, medial temporal lobe, fornix, and corpus callosum. Limitations of current neuropsychological techniques for the clinical assessment of memory and executive function are explored and recommendations for improved research designs offered, that may enhance the study of long-term neuropsychological sequelae of concussion. (JINS, 2008, 14, 1-22.)

show abstract

The neurophysiology of concussion

Cited by 309 publications

References 266 publications

Role of Akt and Mammalian Target of Rapamycin in Functional Outcome after Concussive Brain Injury in Mice

Role of Akt and Mammalian Target of Rapamycin in Functional Outcome after Concussive Brain Injury in Mice

Multiple Episodes of Mild Traumatic Brain Injury Result in Impaired Cognitive Performance in Mice

Neuropsychology and clinical neuroscience of persistent post-concussive syndrome

Contact Info

Product

Resources

About