Simultaneous triple therapy for the treatment of status epilepticus

Autor: Lucie Suchomelova, Jerome Niquet, Lucille A. Lumley, Roger A. Baldwin, Claude G. Wasterlain, Keith M. Norman
Rok vydání: 2017
Předmět:
Male
0301 basic medicine
Neurodegenerative
Pharmacology
Rats
Sprague-Dawley
Status Epilepticus
0302 clinical medicine
Neurons
GABAA receptor
Pilocarpine
Electroencephalography
Combined Modality Therapy
Treatment Outcome
Neurology
6.1 Pharmaceuticals
Anesthesia
Combination
NMDA receptor
Drug Therapy
Combination
Anticonvulsants
Ketamine
Drug
medicine.symptom
medicine.drug
Agonist
medicine.drug_class
Midazolam
Clinical Sciences
Status epilepticus
Article
lcsh:RC321-571
Dose-Response Relationship
03 medical and health sciences
Drug Therapy
medicine
Animals
Refractory status epilepticus
Maze Learning
lcsh:Neurosciences. Biological psychiatry. Neuropsychiatry
Valproate
Epilepsy
Neurology & Neurosurgery
Dose-Response Relationship
Drug
Animal
business.industry
Valproic Acid
Neurosciences
Antagonist
Evaluation of treatments and therapeutic interventions
Cholinergic seizures
Brain Waves
Rats
Brain Disorders
Disease Models
Animal
030104 developmental biology
nervous system
Phenytoin
Disease Models
Sprague-Dawley
business
030217 neurology & neurosurgery
Zdroj: Niquet, J; Baldwin, R; Norman, K; Suchomelova, L; Lumley, L; & Wasterlain, CG. (2017). Simultaneous triple therapy for the treatment of status epilepticus. NEUROBIOLOGY OF DISEASE, 104, 41-49. doi: 10.1016/j.nbd.2017.04.019. UCLA: Retrieved from: http://www.escholarship.org/uc/item/8zd476cb
Neurobiology of Disease, Vol 104, Iss, Pp 41-49 (2017)
ISSN: 0969-9961
DOI: 10.1016/j.nbd.2017.04.019
Popis: Early maladaptive internalization of synaptic GABAA receptors (GABAA R) and externalization of NMDA receptors (NMDAR) may explain the time-dependent loss of potency of standard anti-epileptic drugs (AED) in refractory status epilepticus (SE). We hypothesized that correcting the effects of changes in GABAAR and NMDAR would terminate SE, even when treatment is delayed 40 minutes. SE was induced in adult Sprague-Dawley rats with a high dose of lithium and pilocarpine. The GABAAR agonist midazolam, the NMDAR antagonist ketamine and the AED valproate were injected 40 min after SE onset in combination or as monotherapy. The midazolam-ketamine-valproate combination was more efficient than triple-dose midazolam, ketamine or valproate monotherapy or higher-dose dual therapy in reducing several parameters of SE severity. Triple therapy also reduced SE-induced acute neuronal injury and spatial memory deficits. In addition, simultaneous triple therapy was more efficient than sequential triple therapy: giving the three drugs simultaneously was more efficient at stopping seizures than the standard practice of giving them sequentially. Furthermore, midazolam-ketamine-valproate therapy suppressed seizures far better than the midazolam-fosphenytoin-valproate therapy, which follows evidence-based AES guidelines. These results show that a treatment aimed at correcting maladaptive GABAAR and NMDAR trafficking can reduce the severity of SE and its long-term consequences.
Databáze: OpenAIRE
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