Mechanism of neuronal damage following mild in-vitro traumatic neuronal injury.
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Thus, sublethal stretch injury results in elevated ROS that are tolerated by the cultures, but imparts neurons with decreased resiliency to secondary excitotoxic insults specifically associated with NMDAR-triggered NO production via the coupling of NMDA receptors to PSD-95. The result of this interaction is further ROS production specifically associated with toxic nitrogen radical species, leading to non-apoptotic cell death.Traumatic brain injury mechanisms are categorized into primary injury and secondary injury. Primary injury is defined as the injury resulting from the initial mechanical event (direct injury), whereas secondary injury is the delayed damage arising from the signaling pathways triggered by the primary insult. Unlike primary injury, secondary injury may be amenable to treatment and pharmacological intervention.Using primary cortical neuronal cultures grown on flexible silastic membranes, we established parameters needed to mechanically stretch cells to a degree and duration that itself produces sublethal injury. Although the cells survived the stretch, it imparted them with an enhanced vulnerability to secondary excitotoxic insults specifically associated with NMDAR activity. The increased vulnerability to NMDA was dependent on Ca2+ influx through NMDARs. Stretch had no detectable effect on NMDA receptor function or synaptic activity, indicating that postsynaptic mechanisms downstream from NMDARs may be responsible.Following sublethal stretch, neurons exhibited a transient reduction in mitochondrial potential. Secondary NMDA insults prevented complete mitochondrial repolarization, and cultures exhibited both TUNEL staining and DNA laddering on gel electrophoresis---hallmarks of apoptosis. However, caspase 3 activation was not observed, and treatment with a pan caspase inhibitor z-vad-FMK did not attenuate vulnerability to NMDA, suggesting against a classical apoptotic mechanism. Moreover, apoptosis-inducing factor (AIF) and endonuclease-g did not translocate into the nucleus, suggesting against caspase independent apoptotic mechanisms.Stretched neurons exhibited a rapid production of reactive oxygen species (ROS) which were well tolerated by the cultures. The secondary NMDA insult caused greater ROS production and increased cell death, TUNEL immunoreactivity, and protein nitration. NOS inhibition reduced the enhanced vulnerability and DNA fragmentation. Dissociating NMDARs from PSD-95 with TAT fusion peptides also reduced the enhanced vulnerability of stretched cultures to NMDA, and reduced ROS production and nitrotyrosine immunoreactivity.
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Introduction. Mild traumatic brain injury (TBI) occurs frequently as an outcome from military, sports, and recreational activities, and vehicular accidents, and can lead to a variety of adverse sensory, motor, cognitive and emotional outcomes (Faul et al., ; Risdall and Menon, ; Johnson et al., ).Mild TBI involves either brief or no loss of consciousness and causes minimal overt Cited by: Traumatic brain injury (TBI) encompasses structural brain damage or physiological alteration in brain function resulting from an external force.
1 Worldwide, the leading causes of TBI are falls and motor vehicle accidents, resulting in an estimated 10 million deaths and/or hospitalizations annually 2; TBI is the leading cause of mortality and morbidity for persons under 45 y of age. 3 TBI is a Cited by: Traumatic brain injury causes diffuse axonal injury and loss of cortical neurons.
These features are well recognized histologically, but their in vivomonitoring remains challenging. In vivocortical microdialysis samples the extracellular fluid adjacent to neurons and by: Despite its enormous incidence, mild traumatic brain injury is not well understood.
One aspect that needs more definition is how the mechanical energy during injury affects neural circuit function. Recent developments in cellular imaging probes provide an opportunity to assess the dynamic state of neural networks with single-cell resolution.
In this article, we developed imaging methods to Cited by: Abstract. Traumatic brain injury (TBI) is unique among neurological afflictions in that it is induced by a discrete physical event. To understand the relationship between mechanical loading and the evolution of structural and functional alterations of neural cells, TBI researchers have utilized in vitro Author: Daniel E.
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Bonder, Carolyn E. Keating, Namas Chandra, D. Kacy Cullen, Bryan J. Pfister. Traumatic Neuronal Injury In Vitro 10 fetal bovine serum, 2 mM glutamine, and 21 mM glucose. Cells dispersed by trituration were plated in Falcon Primaria 15 mm wells (24 wells per plate) at an initial density of about x cells per well.
Neuron Review Traumatic Brain Injury and the Neuronal Microenvironment: A Potential Role for Neuropathological Mechanotransduction Matthew A. Hemphill, 1Stephanie Dauth, Chung Jong Yu, Borna E. Dabiri,1 and Kevin Kit Parker1,* 1Disease Biophysics Group, Wyss Institute for Biologically Inspired Engineering, School of Engineering and Applied Sciences, Harvard University, Cambridge, MA.
Following injury, the growth cone extension is effectively inhibited by myelin-associated proteins, such as Nogo-A, myelin-associated glycoprotein (MAG) and oligodendrocyte-myelin glycoprotein (OMgp), which activate the growth inhibitory Nogo receptor, and therefore slow and prevent axonal sprouting [ 22 ].
Main Text Introduction. A blow to the head may potentiate traumatic brain injury (TBI), estimated to affect million people annually in the United States (Faul et al., ) and perpeople annually in Europe (Tagliaferri et al., ).TBI is categorized as mild, moderate, or severe based on Mechanism of neuronal damage following mild in-vitro traumatic neuronal injury.
book symptoms often in combination with imaging and postmortem histology. This is proposed to lead to neuronal injury by depositing redox active iron in neurological tissue. The neuropathology and mechanisms of neuronal injury have been studied in neuroferritinopathy due to the insC mutation and a case due to the insTC mutation (Vidal et al., ; Mancuso et al., ).
In both cases, neuronal loss and. The Centers for Disease Control and Prevention estimates that as many as million people in the United States experience a traumatic brain injury (TBI) each year, over 15% of which are thought to be sports-related.
Despite the relatively high prevalence of these injuries, however, it seems we are just beginning to appreciate the true extent of the effects they can have on the brain.
The disease mechanism of traumatic brain injury is poorly understood and therapeutic interventions are non-existent. Cellular mechanotransduction and the cellular mechanical environment likely play a critical role in pathology and clinical symptoms, yet their explicit involvement remains unexplored.
The multiplicity and complexity of secondary injury processes following brain trauma in vivo make it difficult to elucidate the roles of specific injury mechanisms. As with other areas of CNS injury, such as ischemia, this has led to the development of in vitro models. We developed a new in vitro model of neuronal injury using NT2-N cells to examine the effects of hydrodynamic loading rate on intraneuronal calcium dynamics and lactate dehydrogenase (LDH) release.
Our apparatus consisted of a parallel disk viscometer which induced fluid shear stress with well-defined magnitudes and loading rates to cultured cells. Brain edema and the associated increase in intracranial pressure are major consequences of traumatic brain injury (TBI) that accounts for most early deaths after TBI.
We recently showed that acute severe trauma to cultured astrocytes results in cell swelling. We further examined whether trauma induces cell swelling in neurons and microglia. We found that severe trauma also. Therapeutic hypothermia (TH) is an attractive target for mild traumatic brain injury (mTBI) treatment, yet significant gaps in our mechanistic understanding of TH, especially at the cellular level, remain and need to be addressed for significant forward progress to be made.
Using a recently-established 3D in-vitro neural hydrogel model for mTBI we investigated the efficacy of TH after. “Notably, there are no objective biomarkers to quantify neuronal damage or other types of central nervous pathology in individuals with PCS,” the authors, led by Pashtun Shahim, MD, PhD, of.
Further, this article presents an overview from in vivo and in vitro models of CNS injuries suggesting that administration of calpain inhibitors during the initial h period following injury can attenuate injury-induced derangements of neuronal structure and function.
Lastly, this review addresses the potential contribution of other proteases. Because the molecular mechanisms of delayed post-traumatic neuronal cell death are still poorly understood, we investigated whether apoptosis-inducing factor (AIF), a pro-apoptotic mitochondrial molecule and the key factor in the caspase-independent, cell death signaling pathway, plays a causal role in neuronal death following TBI.
Dark shrunken neurons and swollen astrocytes were detected within cortical areas overlying the evolving contusion, CA3 and CA4 hippocampal subsectors, and lateral thalamus.
Ultrastructural studies obtained evidence for irreversible neuronal injury and mechanical damage to vessel walls at this early posttraumatic period. Astrocytes, once believed to serve only as “glue” for the structural support of neurons, have been demonstrated to serve critical functions for the maintenance and protection of neurons, especially under conditions of acute or chronic injury.
There are at least seven distinct mechanisms by which astrocytes protect neurons from damage; these are (1) protection against glutamate toxicity, (2. Mechanisms and Consequences of Neuronal Stretch Injury In VitroDiffer with the Model of Trauma DONNA M. GEDDES-KLEIN,1 KIMBERLY B.
SCHIFFMAN,1 and DAVID F. MEANEY1,2 ABSTRACT The deformation to the brain that occurs during traumatic brain injury (TBI) results in a complex strain distribution throughout the brain tissue. Neuroinflammation is an important secondary mechanism that is a key mediator of the long-term consequences of neuronal injury that occur in traumatic brain injury (TBI).
Microglia are highly plastic cells with dual roles in neuronal injury and recovery. The incidence and mortality of strokes have increased over the past three decades in China.
Ischemic strokes can cause a sequence of detrimental events in patients, including increased permeability and dysfunction of the blood-brain barrier, brain edema, metabolic disturbance, endoplasmic reticulum stress, autophagy, oxidative stress, inflammation, neuron death and apoptosis, and.
Edema is an important target for clinical intervention after traumatic brain injury (TBI). We used in vivo cellular resolution imaging and electrophysiological recording to examine the ionic mechanisms underlying neuronal edema and their effects on neuronal and network excitability after controlled cortical impact (CCI) in mice.
Traumatic brain injury (TBI) affects % of the world population each year.
Description Mechanism of neuronal damage following mild in-vitro traumatic neuronal injury. EPUB
1,2 The majority of these injuries are categorized as mild; nonetheless, even the mild injuries can result in systemic problems, such as memory loss, as a consequence of neuronal loss and connectivity changes.
Most of the neurons are not lost immediately but rather days following the injury. 1. Introduction. Responses to injury and disease in the central nervous system (CNS) involve multiple neural and non-neural cell types that interact over time in an effort to maintain homeostasis, protect viable cells, clear debris and preserve function (Burda and Sofroniew, ).Astrocytes are pivotal responders to all forms of CNS insults through diverse potential changes.
Traumatic brain injury (TBI) impacts the lives of to 2 million new individuals each year; 75, toof these are classified as severe, and will suffer enduring severe spasticity in addition to cognitive, vestibulomotor (balance), and other motor impairments. Following TBI, the onset of s.
Cell death was examined by studying the spinal cords of rats subjected to traumatic insults of mild to moderate severity. Within minutes after mild weight drop impact (a 10 gm weight falling mm), neurons in the immediate impact area showed a loss of cytoplasmic Nissl substances. Over the next 7 d, this lesion area expanded and cavitated.
Terminal deoxynucleotidyl transferase (TdT. Traumatic brain injury (TBI) is a leading cause of death and disability worldwide, affecting all ages and demographics. In the United States alone, approximately million new cases are reported yearly,– resulting in death in roughly 5% of individuals, long-term disability in greater than 40%, and 25% of affected adults unable to return to work 1 year following the injury.
Previous studies used in vitro models of cerebral ischemia to examine the neuroprotective properties of volatile anesthetics, but most examined surrogates of neuronal injury such as elevation in intracellular calcium 10or recovery of neurotransmission 12instead of cell survival.
These studies examined only immediate changes in injury surrogates, although in vivo, injury can evolve over hours. Traumatic brain injury is a leading cause of morbidity and death in both industrialized and developing countries.
To date, there is no targeted pharmacological treatment that effectively limits the progression of secondary injury.
Details Mechanism of neuronal damage following mild in-vitro traumatic neuronal injury. FB2
The delayed progression of deterioration of grey and white matter gives hope that a meaningful intervention can be applied in a realistic timeframe following initial.
Cerium oxide nanoparticles (CeONPs) increase neuronal survival and improve glutamate signaling after in vitro traumatic injury. In panel a, mixed organotypic brain cell cultures underwent in vitro traumatic brain injury (TBI) at mild ( mm stretch) and moderate ( mm stretch) injury levels.
CeONPs were delivered 1 h post-injury, at the.
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