Article ID | Journal | Published Year | Pages | File Type |
---|---|---|---|---|
6022188 | Neurobiology of Disease | 2014 | 8 Pages |
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 (10Â mg/kg or 2Â mg/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, 48Â h and 96Â h following status epilepticus. Volume measurements were performed between 18 and 21Â days 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 3Â weeks after the initial insult. The T2 measurements at 2Â days and 4Â days in the hippocampus correlated with hippocampal volumes at 3Â weeks. 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 2Â mg/kg and 10Â mg/kg dexamethasone respectively. These findings suggest that dexamethasone can exacerbate the acute cerebral edema and brain injury associated with status epilepticus.
Keywords
NSAIDSDEXCSEFSEETLFOVCOX-2IκBROIsinflammationMRIstatus epilepticusEpilepsyBiomarkerMagnetic resonance imagingNon-steroidal anti-inflammatory drugsDexamethasoneecho timeRepetition timeBlood–brain barrierBBBFast spin-echoConvulsive status epilepticusCyclooxygenase-2Regions Of InterestField of viewCorticosteroids
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Authors
B.A. Duffy, K.P. Chun, D. Ma, M.F. Lythgoe, R.C. Scott,