Excitatory synaptic transmission and network activity are depressed following mechanical injury in cortical neurons

Goforth, Paulette B.; Ren, Jianhua; Schwartz, Benjamin S.; Satin, Leslie S.

doi:10.1152/jn.00467.2010

Cited by 63 publications

(49 citation statements)

References 70 publications

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“…8 Campbell and colleagues 8 reported that 24 h post-TBI, there was a 21% loss in total spines on the AO dendrites of layer II/III cortical neurons, and loss of synaptic activity has also been reported in vitro, where stretch injury of hippocampal neurons results in a prolonged loss of excitatory synaptic transmission. 23 In the present study, we found that dendritic spine loss occurred over a wide area after a focal TBI, including a significant loss of dendritic spines in the contralateral cortex and hippocampus. We believe that our extensive loss of excitatory synapse sites is because CCI causes a much more severe injury than that seen with the unilateral fluid percussion injury model.…”

Section: Discussionsupporting

confidence: 55%

Controlled Cortical Impact Results in an Extensive Loss of Dendritic Spines that Is Not Mediated by Injury-Induced Amyloid-Beta Accumulation

Winston

Chellappa

Wilkins

et al. 2013

Journal of Neurotrauma

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The clinical manifestations that occur after traumatic brain injury (TBI) include a wide range of cognitive, emotional, and behavioral deficits. The loss of excitatory synapses could potentially explain why such diverse symptoms occur after TBI, and a recent preclinical study has demonstrated a loss of dendritic spines, the postsynaptic site of the excitatory synapse, after fluid percussion injury. The objective of this study was to determine if controlled cortical impact (CCI) also resulted in dendritic spine retraction and to probe the underlying mechanisms of this spine loss. We used a unilateral CCI and visualized neurons and dendtritic spines at 24 h post-injury using Golgi stain. We found that TBI caused a 32% reduction of dendritic spines in layer II/III of the ipsilateral cortex and a 20% reduction in the dendritic spines of the ipsilateral dentate gyrus. Spine loss was not restricted to the ipsilateral hemisphere, however, with similar reductions in spine numbers recorded in the contralateral cortex (25% reduction) and hippocampus (23% reduction). Amyloid-b (Ab), a neurotoxic peptide commonly associated with Alzheimer disease, accumulates rapidly after TBI and is also known to cause synaptic loss. To determine if Ab contributes to spine loss after brain injury, we administered a c-secretase inhibitor LY450139 after TBI. We found that while LY450139 administration could attenuate the TBI-induced increase in Ab, it had no effect on dendritic spine loss after TBI. We conclude that the acute, global loss of dendritic spines after TBI is independent of c-secretase activity or TBI-induced Ab accumulation.

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Section: Discussionsupporting

confidence: 55%

Controlled Cortical Impact Results in an Extensive Loss of Dendritic Spines that Is Not Mediated by Injury-Induced Amyloid-Beta Accumulation

Winston

Chellappa

Wilkins

et al. 2013

Journal of Neurotrauma

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“…28 In vitro stretch injury of neurons also causes a prolonged loss of excitatory synaptic transmission. 29 In the present study, we focused our spine counts on layers II/III of the cortex and report that a single mTBI causes a 13% loss of spines in the AO dendrites in young male mice, with a greater spine loss occurring after mTBI on the same dendrites in aged male mice. Combined together, these studies of dendritic spines after TBI show that this is a common phenomenon that occurs in a severe TBI model (controlled cortical impact), 18,30 a moderate TBI model (FPI), 28 and our mild TBI model.…”

Section: Rapid But Temporary Synaptic Loss Occurs After a Single Mtbimentioning

confidence: 87%

Dendritic Spine Loss and Chronic White Matter Inflammation in a Mouse Model of Highly Repetitive Head Trauma

Winston

Noël

Neustadtl

et al. 2016

The American Journal of Pathology

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Mild traumatic brain injury (mTBI) is an emerging risk for chronic behavioral, cognitive, and neurodegenerative conditions. Athletes absorb several hundred mTBIs each year; however, rodent models of repeat mTBI (rmTBI) are often limited to impacts in the single digits. Herein, we describe the effects of 30 rmTBIs, examining structural and pathological changes in mice up to 365 days after injury. We found that single mTBI causes a brief loss of consciousness and a transient reduction in dendritic spines, reflecting a loss of excitatory synapses. Single mTBI does not cause axonal injury, neuroinflammation, or cell death in the gray or white matter. Thirty rmTBIs with a 1-day interval between each mTBI do not cause dendritic spine loss; however, when the interinjury interval is increased to 7 days, dendritic spine loss is reinstated. Thirty rmTBIs cause white matter pathology characterized by positive silver and Fluoro-Jade B staining, and microglial proliferation and activation. This pathology continues to develop through 60 days, and is still apparent at 365 days, after injury. However, rmTBIs did not increase b-amyloid levels or tau phosphorylation in the 3xTg-AD mouse model of Alzheimer disease. Our data reveal that single mTBI causes a transient loss of synapses, but that rmTBIs habituate to repetitive injury within a short time period. rmTBI causes the development of progressive white matter pathology that continues for months after the final impact. (Am J Pathol 2016, 186: 552e567; http://dx.doi.org/ 10.1016/j.ajpath.2015 Athletes participating in contact sports are at high risk of exposure to large numbers of concussive and subconcussive mild traumatic brain injuries (mTBIs). Recent studies using head impact telemetry systems have begun to reveal how many head impacts an individual football player can receive in the process of playing his or her sport. In a study of high school football players, the number of helmet impacts >20 g recorded in a single season ranged from a low of 226 (average, 4.7 per session) to a high of 1855 (average, 38.6 per session). 1 Most of these impacts do not result in the clinical diagnosis of a concussion; however, it is not known if the cumulative effects of these impacts can result in increased damage to the brain. mTBI has been extensively modeled in mice and rats. 2 Most of these rodent models use fewer than five mTBIs, and report adverse events, including intracerebral bleeding, skull fractures, severe axonal injury, neuronal cell death, and increased mortality.

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“…An in vitro model of TBI mechanical with cultured cortical neurons, resulted in the membrane composition of glutamatergic receptors. That is, after stretch injury, calcium-permeable AMPA receptors were upregulated in plasma membranes [120,121]. …”

Section: Pathophysiology Of Memory Impairment After Tbimentioning

confidence: 99%

Pathophysiology and Treatment of Memory Dysfunction After Traumatic Brain Injury

Paternò

Folweiler

Cohen

2017

Curr Neurol Neurosci Rep

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Memory is fundamental to everyday life, and cognitive impairments resulting from traumatic brain injury (TBI) have devastating effects on TBI survivors. A contributing component to memory impairments caused by TBI are alterations in the neural circuits associated with memory function. In this review, we aim to bring together experimental findings that characterize behavioral memory deficits and the underlying pathophysiology of memory-involved circuits after TBI. While there is little doubt that TBI causes memory and cognitive dysfunction, it is difficult to conclude which memory phase i.e., encoding, maintenance or retrieval is specifically altered by TBI. This is most likely due to variation in behavioral protocols and experimental models. Additionally we review a selection of experimental treatments that hold translational potential to mitigate memory dysfunction following injury.

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Excitatory synaptic transmission and network activity are depressed following mechanical injury in cortical neurons

Cited by 63 publications

References 70 publications

Controlled Cortical Impact Results in an Extensive Loss of Dendritic Spines that Is Not Mediated by Injury-Induced Amyloid-Beta Accumulation

Controlled Cortical Impact Results in an Extensive Loss of Dendritic Spines that Is Not Mediated by Injury-Induced Amyloid-Beta Accumulation

Dendritic Spine Loss and Chronic White Matter Inflammation in a Mouse Model of Highly Repetitive Head Trauma

Pathophysiology and Treatment of Memory Dysfunction After Traumatic Brain Injury

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