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Dexamethasone exacerbates cerebral edema and brain injury following lithium-pilocarpine induced status epilepticus.

Duffy, BA; Chun, KP; Ma, D; Lythgoe, MF; Scott, RC; (2014) Dexamethasone exacerbates cerebral edema and brain injury following lithium-pilocarpine induced status epilepticus. Neurobiol Dis , 63 pp. 229-236. 10.1016/j.nbd.2013.12.001. Green open access

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Abstract

Anti-inflammatory therapies are the current most plausible drug candidates for anti-epileptogenesis and neuroprotection following prolonged seizures. Given that vasogenic edema is widely considered to be detrimental for outcome following status epilepticus, the anti-inflammatory agent dexamethasone is sometimes used in clinic for alleviating cerebral edema. In this study we perform longitudinal magnetic resonance imaging in order to assess the contribution of dexamethasone on cerebral edema and subsequent neuroprotection following status epilepticus. Lithium-pilocarpine was used to induce status epilepticus in rats. Following status epilepticus, rats were either post-treated with saline or with dexamethasone sodium phosphate (10mg/kg or 2mg/kg). Brain edema was assessed by means of magnetic resonance imaging (T2 relaxometry) and hippocampal volumetry was used as a marker of neuronal injury. T2 relaxometry was performed prior to, 48h and 96h following status epilepticus. Volume measurements were performed between 18 and 21days after status epilepticus. Unexpectedly, cerebral edema was worse in rats that were treated with dexamethasone compared to controls. Furthermore, dexamethasone treated rats had lower hippocampal volumes compared to controls 3weeks after the initial insult. The T2 measurements at 2days and 4days in the hippocampus correlated with hippocampal volumes at 3weeks. Finally, the mortality rate in the first week following status epilepticus increased from 14% in untreated rats to 33% and 46% in rats treated with 2mg/kg and 10mg/kg dexamethasone respectively. These findings suggest that dexamethasone can exacerbate the acute cerebral edema and brain injury associated with status epilepticus.

Type: Article
Title: Dexamethasone exacerbates cerebral edema and brain injury following lithium-pilocarpine induced status epilepticus.
Open access status: An open access version is available from UCL Discovery
DOI: 10.1016/j.nbd.2013.12.001
Publisher version: http://dx.doi.org/10.1016/j.nbd.2013.12.001
Additional information: © 2013 The Authors. Published by Elsevier Inc. All rights reserved. This is an open-access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited.
Keywords: BBB, Biomarker, COX-2, CSE, Corticosteroids, DEX, Epilepsy, FOV, Inflammation, IκB, MRI, NSAIDs, ROIs, SE, T(2), TE, TEeff, TR, blood–brain barrier, convulsive status epilepticus, cyclooxygenase-2, dexamethasone, echo time, echo-train length, effective echo time, etl, fast spin-echo, field of view, fse, inhibitor of kappa-B, magnetic resonance imaging, non-steroidal anti-inflammatory drugs, rHCV, regions of interest, relative hippocampal volume, repetition time, status epilepticus, transverse magnetisation relaxation time constant
UCL classification: UCL
UCL > Provost and Vice Provost Offices
UCL > Provost and Vice Provost Offices > School of Life and Medical Sciences
UCL > Provost and Vice Provost Offices > School of Life and Medical Sciences > Faculty of Medical Sciences
UCL > Provost and Vice Provost Offices > School of Life and Medical Sciences > Faculty of Medical Sciences > Div of Medicine
UCL > Provost and Vice Provost Offices > School of Life and Medical Sciences > Faculty of Medical Sciences > Div of Medicine > Experimental and Translational Medicine
UCL > Provost and Vice Provost Offices > School of Life and Medical Sciences > Faculty of Population Health Sciences
UCL > Provost and Vice Provost Offices > School of Life and Medical Sciences > Faculty of Population Health Sciences > UCL GOS Institute of Child Health
UCL > Provost and Vice Provost Offices > School of Life and Medical Sciences > Faculty of Population Health Sciences > UCL GOS Institute of Child Health > Developmental Neurosciences Dept
URI: https://discovery.ucl.ac.uk/id/eprint/1418507
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