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Cited by 150Epilepsy research and treatmentDiet and metabolism studiesPharmacological Effects and Toxicity Studies

Efficacy of Anti-Inflammatory Therapy in a Model of Acute Seizures and in a Population of Pediatric Drug Resistant Epileptics

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Marchi, Nicola, Granata, Tiziana, Freri, Elena, Ciusani, Emilio, Ragona, Francesca, Puvenna, Vikram, Teng, Quingshan, Alexopolous, Andreas +1 more·2011·PLoS ONE
DOI 10.1371/journal.pone.0018200PMC PMC3065475
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Abstract

Targeting pro-inflammatory events to reduce seizures is gaining momentum. Experimentally, antagonism of inflammatory processes and of blood-brain barrier (BBB) damage has been demonstrated to be beneficial in reducing status epilepticus (SE). Clinically, a role of inflammation in the pathophysiology of drug resistant epilepsies is suspected. However, the use anti-inflammatory drug such as glucocorticosteroids (GCs) is limited to selected pediatric epileptic syndromes and spasms. Lack of animal data may be one of the reasons for the limited use of GCs in epilepsy. We evaluated the effect of the CG dexamethasone in reducing the onset and the severity of pilocarpine SE in rats. We assessed BBB integrity by measuring serum S100β and Evans Blue brain extravasation. Electrophysiological monitoring and hematologic measurements (WBCs and IL-1β) were performed. We reviewed the effect of add on dexamethasone treatment on a population of pediatric patients affected by drug resistant epilepsy. We excluded subjects affected by West, Landau-Kleffner or Lennox-Gastaut syndromes and Rasmussen encephalitis, known to respond to GCs or adrenocorticotropic hormone (ACTH). The effect of two additional GCs, methylprednisolone and hydrocortisone, was also reviewed in this population. When dexamethasone treatment preceded exposure to the convulsive agent pilocarpine, the number of rats developing status epilepticus (SE) was reduced. When SE developed, the time-to-onset was significantly delayed compared to pilocarpine alone and mortality associated with pilocarpine-SE was abolished. Dexamethasone significantly protected the BBB from damage. The clinical study included pediatric drug resistant epileptic subjects receiving add on GC treatments. Decreased seizure frequency (≥ 50%) or interruption of status epilepticus was observed in the majority of the subjects, regardless of the underlying pathology. Our experimental results point to a seizure-reducing effect of dexamethasone. The mechanism encompasses improvement of BBB integrity. Our results also suggest that add on GCs could be of efficacy in controlling pediatric drug resistant seizures.

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  • Multiple anti-inflammatory treatment strategies have demonstrated the beneficial effect of maintaining blood-brain barrier integrity in epilepsy.

    “Multiple anti-inflammatory treatment strategies have demonstrated the beneficial effect of maintaining BBB integrity in this condition (393).”

    From Blood-Brain Barrier: From Physiology to Disease and Back (2019) · cites this paper as [393]

    The Results section ('Evaluation of blood-brain barrier damage'; page not provided) reports reduced BBB damage and seizures in rats pretreated with dexamethasone. The paper also evaluates several anti-inflammatory treatments in children, but the Discussion says that restored BBB integrity as a mechanism in patients remains a hypothesis requiring a prospective MRI study. It does not demonstrate that multiple treatment strategies maintained BBB integrity. (LLM, conf=0.86)

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Authors
Marchi, N., Granata, T., Freri, E., Ciusani, E., Ragona, F., Puvenna, V., Teng, Q., Alexopolous, A., & Janigro, D.
Affiliations
  • Cleveland Clinic (US)
  • Fondazione IRCCS Istituto Neurologico Carlo Besta (IT)
Corresponding author
Janigro, Damir
ORCID
Venue
PLoS ONE
Publisher
Public Library of Science (PLoS)
Published
2011-03-28
Volume
6
Issue
3
Pages
e18200
ISSN
1932-6203 (ISSN-L)
DOI
10.1371/journal.pone.0018200
PMC
PMC3065475
OpenAlex
W2020189206
Cited by
150
References
0
Citations by year
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FWCI
12.11
Type
journal article
Language
en
Open access
Licence
Locations
  • PLoS ONE (publishedVersion, cc-by)
  • PubMed Central (publishedVersion, cc-by)
  • PubMed (publishedVersion)
  • DOAJ (DOAJ: Directory of Open Access Journals) (submittedVersion, cc-by-sa)
  • Figshare (submittedVersion, cc-by)
Funders
  • Cleveland Clinic
  • Washington State University
  • National Institute of Neurological Disorders and Stroke (R01NS043284, R01 NS 43284, R01 NS38195, R01NS038195)
  • Eunice Kennedy Shriver National Institute of Child Health and Human Development (R21HD057256)
Topics
  • Health Sciences › Medicine › Psychiatry and Mental health › Epilepsy research and treatment
  • Health Sciences › Medicine › Physiology › Diet and metabolism studies
  • Health Sciences › Medicine › Pediatrics, Perinatology and Child Health › Pharmacological Effects and Toxicity Studies
Keywords
anti-inflammatory therapy, drug-resistant epilepsy, pediatric epilepsy, status epilepticus, dexamethasone, glucocorticoids, pilocarpine-induced seizures, blood-brain barrier integrity, S100β, Evans blue extravasation, methylprednisolone, cortisol, seizure frequency reduction
MeSH terms
Acute Disease, Adrenal Cortex Hormones, Adrenocorticotropic Hormone, Animals, Anti-Inflammatory Agents, Blood-Brain Barrier, Child, Dexamethasone, Disease Models, Animal, Drug Resistance, Electroencephalography, Humans, Pilocarpine, Radiography, Seizures, Time Factors, Treatment Outcome, Rats

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