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.
Highlights
Inflammation has been suggested to play a major role in epileptogenesis (Ravizza et al, 2011; Vezzani et al, 2013)
In this study we investigate whether using a broad-spectrum antiinflammatory agent can reduce vasogenic edema, assessed by quantitative transverse magnetization relaxation time constant (T2) measurements following pilocarpine induced status epilepticus (SE) in rats, and whether these changes predict final hippocampal volumes
The aims of Experiment 1 were to test the effects of dexamethasone given following SE at a dose of 10 mg/kg on transverse magnetisation relaxation time constant (T2) and hippocampal volume
Summary
Inflammation has been suggested to play a major role in epileptogenesis (Ravizza et al, 2011; Vezzani et al, 2013). Into the parenchyma across an impaired blood–brain barrier (BBB) leading to impaired astrocyte function and altered potassium homeostasis (Cacheaux et al, 2009; David et al, 2009; Friedman et al, 2009; Ivens et al, 2007; Seiffert et al, 2004; van Vliet et al, 2007). This leads to the hypothesis that anti-inflammatory therapies which help to alleviate vasogenic edema are likely to be anti-epileptogenic or neuroprotective following convulsive status epilepticus (CSE). A variety of anti-inflammatory drugs have been shown to be neuroprotective or anti-epileptogenic following status epilepticus. A selective cyclooxygenase-2 (COX-2) inhibitor administered for 18 days following lithium-pilocarpine induced SE is neuroprotective (but not anti-epileptogenic) (Polascheck et al, 2010), and Celecoxib reduces neuronal injury and microglia activation when administered
Sign-in/Register to view highlights & summary Sign-in/Register to access full text options 
Talk to us
Join us for a 30 min session where you can share your feedback and ask us any queries you have
Schedule a callDisclaimer: All third-party content on this website/platform is and will remain the property of their respective owners and is provided on "as is" basis without any warranties, express or implied. Use of third-party content does not indicate any affiliation, sponsorship with or endorsement by them. Any references to third-party content is to identify the corresponding services and shall be considered fair use under The CopyrightLaw.
