Inhibition of Proteasomal Glucocorticoid Receptor Degradation Restores Dexamethasone-Mediated Stabilization of the Blood–Brain Barrier After Traumatic Brain Injury*

Thal, Serge C.; Schaible, Eva-Verena; Neuhaus, Winfried; Scheffer, David; Brandstetter, Moritz; Engelhard, Kristin; Wunder, Christian; Förster, Carola

doi:10.1097/ccm.0b013e31827ca494

Cited by 53 publications

(51 citation statements)

References 49 publications

(59 reference statements)

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“…Since BBB breakdown is often documented in TBI patients and TBI is often linked to the disruption of the BBB which can result to edema formation 23,24 , the method presented here may specifically be used in conducting BBB studies in relation to TBI.…”

Section: Discussionmentioning

confidence: 99%

Stretch in Brain Microvascular Endothelial Cells (cEND) as an <em>In Vitro</em> Traumatic Brain Injury Model of the Blood Brain Barrier

Salvador¹,

Neuhaus

Foerster³

2013

JoVE

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Citation: Salvador, E., Neuhaus, W., Foerster, C. Stretch in Brain Microvascular Endothelial Cells (cEND) as an In Vitro Traumatic Brain Injury Model of the Blood Brain Barrier. J. Vis. Exp. (80), e50928, doi:10.3791/50928 (2013). AbstractDue to the high mortality incident brought about by traumatic brain injury (TBI), methods that would enable one to better understand the underlying mechanisms involved in it are useful for treatment. There are both in vivo and in vitro methods available for this purpose. In vivo models can mimic actual head injury as it occurs during TBI. However, in vivo techniques may not be exploited for studies at the cell physiology level. Hence, in vitro methods are more advantageous for this purpose since they provide easier access to the cells and the extracellular environment for manipulation.Our protocol presents an in vitro model of TBI using stretch injury in brain microvascular endothelial cells. It utilizes pressure applied to the cells cultured in flexible-bottomed wells. The pressure applied may easily be controlled and can produce injury that ranges from low to severe. The murine brain microvascular endothelial cells (cEND) generated in our laboratory is a well-suited model for the blood brain barrier (BBB) thus providing an advantage to other systems that employ a similar technique. In addition, due to the simplicity of the method, experimental set-ups are easily duplicated. Thus, this model can be used in studying the cellular and molecular mechanisms involved in TBI at the BBB.

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Section: Discussionmentioning

confidence: 99%

Stretch in Brain Microvascular Endothelial Cells (cEND) as an <em>In Vitro</em> Traumatic Brain Injury Model of the Blood Brain Barrier

Salvador¹,

Neuhaus

Foerster³

2013

JoVE

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“…Core temperature was monitored and maintained at 37°C for the duration of the surgery by means of a rectal probe and feedback-controlled heating pad (Hugo Sachs, March-Hugstetten, Germany). Traumatic injury was performed using the controlled cortical impact (CCI) model, as described previously [38], by an experimenter blinded to the treatment groups. Animals were fixed in a stereotactic frame (Kopf Instruments, Tujunga, USA) and a 4mm × 5mm craniotomy window was created using a saline-cooled high-speed drill, along the coronal (anterior) and lambdoid (posterior) sutures and laterally as close as possible to the temporalis muscle insertion.…”

Section: Traumatic Brain Injurymentioning

confidence: 99%

Xenon Improves Neurologic Outcome and Reduces Secondary Injury Following Trauma in an In Vivo Model of Traumatic Brain Injury*

Campos-Pires

Armstrong

Sebastiani

et al. 2015

Critical Care Medicine

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Objectives-To determine the neuroprotective efficacy of the inert gas xenon following traumatic brain injury, and to determine whether application of xenon has a clinically relevant therapeutic time window.Design-Controlled animal study. Setting-University research laboratory. Subjects-Male C57BL/6N mice (n=196)Interventions-75% xenon, 50% xenon or 30% xenon, with 25% oxygen (balance nitrogen) treatment following mechanical brain lesion by controlled cortical impact.Measurements & Main Results-Outcome following trauma was measured using: 1) functional neurological outcome score, 2) histological measurement of contusion volume, 3) analysis of locomotor function and gait. Our study shows that xenon-treatment improves outcome following traumatic brain injury. Neurological outcome scores were significantly (p<0.05) better

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“…(Taylor et al, 2013), which may offer valuable prognostic information (Hannon et al, 2013). Moreover, experimental treatment approaches that down-regulate neuronal / glial GR signalling exert neuroprotective features (Shi et al, 2014), while dexamethasone provides anti-oedematous / BBB-stabilizing effects in animal models of TBI (Thal et al, 2013). Lack of GCs (due to experimental adrenalectomy) has been shown to exert a similar and additive effect to experimentally-induced TBI (fluid percussion injury) on decreasing hippocampal mRNA expression levels of neurotrophin-3 (Grundy et al, 2004) and increasing brain-derived neurotrophic factor (BDNF) (Grundy et al, 2000), while it prevents the post-TBI-induced increase of nerve growth factor (Grundy et al, 2001).…”

Section: Inconsistencies In Our Understanding Of Gc Therapeutics In Nmentioning

confidence: 99%

Temporal control of glucocorticoid neurodynamics and its relevance for brain homeostasis, neuropathology and glucocorticoid-based therapeutics

Kalafatakis

Russell

Ζάρρος³

et al. 2016

Neuroscience & Biobehavioral Reviews

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Glucocorticoids mediate plethora of actions throughout the human body. Within the brain, they modulate aspects of immune system and neuroinflammatory processes, interfere with cellular metabolism and viability, interact with systems of neurotransmission and regulate neural rhythms. The influence of glucocorticoids on memory and emotional behaviour is well known and there is increasing evidence for their involvement in many neuropsychiatric pathologies. These effects, which at times can be in opposing directions, depend not only on the concentration of glucocorticoids but also the duration of their presence, the temporal relationship between their fluctuations, the co-influence of other stimuli, and the overall state of brain activity. Moreover, they are region-and cell type-specific. The molecular basis of such diversity of effects lies on the orchestration of the spatiotemporal interplay between glucocorticoid-and mineralocorticoid receptors, and is achieved through complex dynamics, mainly mediated via the circadian and ultradian pattern of glucocorticoid secretion. More sophisticated methodologies are therefore required to better approach the study of these hormones and improve the effectiveness of glucocorticoid-based therapeutics.

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Inhibition of Proteasomal Glucocorticoid Receptor Degradation Restores Dexamethasone-Mediated Stabilization of the Blood–Brain Barrier After Traumatic Brain Injury*

Cited by 53 publications

References 49 publications

Stretch in Brain Microvascular Endothelial Cells (cEND) as an <em>In Vitro</em> Traumatic Brain Injury Model of the Blood Brain Barrier

Stretch in Brain Microvascular Endothelial Cells (cEND) as an <em>In Vitro</em> Traumatic Brain Injury Model of the Blood Brain Barrier

Xenon Improves Neurologic Outcome and Reduces Secondary Injury Following Trauma in an In Vivo Model of Traumatic Brain Injury*

Temporal control of glucocorticoid neurodynamics and its relevance for brain homeostasis, neuropathology and glucocorticoid-based therapeutics

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