title: Dexamethasone exacerbates cerebral edema and brain injury following lithium-pilocarpine induced status epilepticus.
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, 48 h and 96 h following status epilepticus. Volume measurements were performed between 18 and 21 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 3 weeks after the initial insult. The T2 measurements at 2 days and 4 days in the hippocampus correlated with hippocampal volumes at 3 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 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.
authors: Centre for Advanced Biomedical Imaging (CABI), Department of Medicine, University College London (UCL), UK. Electronic address: ben.duffy.09@ucl.ac.uk.
authors: B A
authors: BA
authors: Duffy
authors: School of Environment and Sustainability, University of Saskatchewan, Canada.
authors: K P
authors: KP
authors: Chun
authors: Centre for Advanced Biomedical Imaging (CABI), Department of Medicine, University College London (UCL), UK; Centre for Medical Image Computing (CMIC), University College London (UCL), UK.
authors: D
authors: D
authors: Ma
authors: Centre for Advanced Biomedical Imaging (CABI), Department of Medicine, University College London (UCL), UK. Electronic address: m.lythgoe@ucl.ac.uk.
authors: M F
authors: MF
authors: Lythgoe
authors: Department of Neurological Sciences, College of Medicine, University of Vermont, Burlington 05405, VT, USA; UCL Institute of Child Health, University College London, London, UK.
authors: R C
authors: RC
authors: Scott
mesh_terms: D000818:Animals; D000893:Anti-Inflammatory Agents / Q000009:adverse effects*; D001929:Brain Edema / Q000209:etiology* / Q000473:pathology; D001930:Brain Injuries / Q000209:etiology*; D002540:Cerebral Cortex / Q000187:drug effects / Q000473:pathology*; D003907:Dexamethasone / Q000009:adverse effects*; D004195:Disease Models, Animal; D007091:Image Processing, Computer-Assisted; D016014:Linear Models; D008094:Lithium / Q000633:toxicity; D008279:Magnetic Resonance Imaging; D008297:Male; D010862:Pilocarpine / Q000633:toxicity; D051381:Rats; D017207:Rats, Sprague-Dawley; D013226:Status Epilepticus / Q000139:chemically induced / Q000150:complications*; D013997:Time Factors
chemical_list: D000893:Anti-Inflammatory Agents; D010862:Pilocarpine; D003907:Dexamethasone; D008094:Lithium
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