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

Duffy, B. A.; Chun, K. P.; Ma, D.; Lythgoe, M. F.; Scott, R. C.

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. © 2013.

• Journal Article Type: Article
• Acceptance Date: Dec 2, 2013
• Publication Date: Jan 1, 2014
• Deposit Date: Jun 17, 2022
• Publicly Available Date: Jun 20, 2022
• Journal: Neurobiology of Disease
• Print ISSN: 0969-9961
• Publisher: Elsevier
• Peer Reviewed: Peer Reviewed
• Volume: 63
• Pages: 229-236
• DOI: https://doi.org/10.1016/j.nbd.2013.12.001
• Keywords: Dexamethasone, cerebral edema, brain injury, lithium-pilocarpine induced status, epilepticus
• Public URL: https://uwe-repository.worktribe.com/output/9431604