2013
DOI: 10.1097/ccm.0b013e31827ca494
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Inhibition of Proteasomal Glucocorticoid Receptor Degradation Restores Dexamethasone-Mediated Stabilization of the Blood–Brain Barrier After Traumatic Brain Injury*

Abstract: The results indicate that the stabilizing effect of glucocorticoids on the blood-brain barrier is hampered after cerebral lesions by proteasomal glucocorticoid receptor degradation in brain endothelial cells and restored by inhibition of proteasomal degradation pathways. The results provide underlying mechanisms for the clinically observed inefficacy of glucocorticoids. The novel combined treatment strategy might help to attenuate trauma-induced brain edema formation and neuronal damage as secondary effects of… Show more

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Cited by 53 publications
(51 citation 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%
“…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%
“…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%
“…(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%