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The efficacy of fructose-1,6-bisphosphate in suppressing status epilepticus in developing rats
Remi Janicot1, Carl E Stafstrom1, Li-Rong Shao1
1Division of Pediatric Neurology, Department of Neurology, The Johns Hopkins University School of Medicine, Baltimore, MD, United States.
Insights
Fructose-1,6-bisphosphate (FBP) effectively stopped seizures in 60% of juvenile rats with status epilepticus (SE). This metabolic therapy shows promise for treating pediatric SE refractory to standard medications.
Area of Science:
- Biochemistry
- Neuroscience
- Pediatric Neurology
Background:
- Pediatric status epilepticus (SE) is difficult to treat, with many cases resistant to current anti-seizure drugs.
- Fructose-1,6-bisphosphate (FBP), a glycolytic intermediate, has demonstrated anticonvulsant properties in adult animal and in vitro seizure models.
Purpose of the Study:
- To evaluate the effectiveness of FBP in controlling seizures in a rat model of juvenile SE.
- To investigate FBP as a potential therapeutic agent for refractory pediatric SE.
Main Methods:
- Juvenile Sprague Dawley rats (postnatal days 11-17) were induced into SE using pilocarpine (300 mg/kg, i.p.).
- Video-electroencephalography (v-EEG) monitored seizure activity.
- FBP (500 or 1000 mg/kg, i.p.) or vehicle was administered 30 minutes into SE, with continued v-EEG monitoring.
Main Results:
- Pilocarpine reliably induced SE in rat pups.
- Neither vehicle nor a lower FBP dose (500 mg/kg) terminated SE.
- A higher FBP dose (1000 mg/kg) terminated SE in 60% of subjects within approximately 15 minutes.
Conclusions:
- Fructose-1,6-bisphosphate (FBP) demonstrates prompt suppression of ongoing seizure activity.
- FBP represents a potential metabolic therapy for improving SE treatment outcomes in juveniles.
- This study supports FBP as a promising alternative for managing refractory pediatric SE.
Purpose:
Treatment of pediatric status epilepticus (SE) remains challenging as up to 50 % of patients are refractory to conventional anti-seizure medications. The glycolytic intermediate, fructose-1,6-bisphosphate (FBP), has been reported to exert significant anticonvulsant effects in both adult animals and in in vitro models of seizures. This study aims to examine FBP efficacy in controlling seizures in a rat model of juvenile SE.
Methods:
Sprague Dawley rats (P11-P17) were injected with pilocarpine (300 mg/kg, i.p.) to induce SE, which was monitored by video-electroencephalography (v-EEG). Thirty minutes into SE, FBP was administrated (500 or 1000 mg/kg, i.p.). v-EEG recording was continued for ∼60 additional minutes to assess the anticonvulsant effect of FBP, compared with vehicle (saline) treatment.
Results:
SE consistently occurred in rat pups 10-15 min after pilocarpine injection and persisted over the 90-min recording period. Neither saline nor a lower dose of FBP (500 mg/kg) treatment stopped behavioral and electrographic seizures. At higher doses (1000 mg/kg), FBP terminated SE in ∼15 min in 60 % (6 of 10) of the rat pups.
Conclusion:
The endogenous glycolytic metabolite, FBP, promptly suppresses ongoing seizure activity and represents a potential alternative metabolic therapy to improve the treatment of SE in the juvenile age range.
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