ArticleEpilepsy & behavior : E&B2025
Efficacy and tolerability of celastrol and edaravone in the multiple-hit rat model of infantile spasms.
Article in Epilepsy & behavior : E&B, 2025. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 5 papers.
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Who cites it
5 citing papers in PubMed.
- Traditional Chinese botanical medicines and plant-derived bioactive compounds in amyotrophic lateral sclerosis: mechanistic evidence, translational challenges, and therapeutic opportunities.Frontiers in pharmacology · 2026Review
- Infantile epileptic spasms syndrome: Mechanisms and therapeutic approaches.Neurotherapeutics : the journal of the American Society for Experimental NeuroTherapeutics · 2026Review
- Celastrol Mitigates Acute Pancreatitis Associated Inflammation by Modulating the IL-34/CSF-1R Axis and Suppressing NF-κB/ERK Signaling.Journal of inflammation research · 2026Article
- The multiple hit model of infantile and epileptic spasms: The 2025 update.Epilepsia open · 2025Article
- The Therapeutic Potential of Celastrol in Central Nervous System Disorders: Highlights from In Vitro and In Vivo Approaches.Molecules (Basel, Switzerland) · 2021Review
Corrections and comments
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Authors and funding
8 authors.
Funding
Abstract
objectiveTo test whether anti-inflammatory and antioxidant drugs that inhibit the nuclear factor kappa light chain enhancer of activated B cells (NF-kB), celastrol and edaravone, suppress spasms and improve developmental outcomes in the multiple-hit rat model of refractory infantile spasms (IS) due to structural lesions.
methodsPostnatal day 3 (PN3) Sprague-Dawley rats were treated according to the multiple-hit IS model protocol. Using a randomized, blinded, vehicle-controlled, dose- and time-response study design, we tested the effects of single celastrol [1, 2, or 4 mg/kg intraperitoneally (i.p.), 10-14 rats/group] or edaravone (1, 10 or 30 mg/kg i.p., 14-17 rats/group) injections vs their vehicles on behavioral and electroclinical spasms and developmental milestones. Video-EEG monitoring was done on PN6-7 (n = 11-12 rats/group). Pulse celastrol treatment effects (PN4: 4 mg/kg, PN5-6: 2 mg/kg/day i.p.) were determined on spasms, developmental milestones and Barnes maze. Celastrol and edaravone pharmacokinetics in plasma and neocortex were assessed. Linear mixed model analysis of raw or normalized log-transformed spasm frequencies, considering repeated observations was used.
resultsSingle (2-4 mg/kg i.p) or pulse celastrol, but not edaravone, reduced behavioral and electroclinical spasms frequencies within 5hrs. Pulse celastrol did not affect spasm-freedom, survival, developmental milestones or Barnes maze performance. Celastrol had erratic i.p. absorption with maximum concentrations observed between 2-4 h, when effects on spasms were seen. Edaravone had low blood-to-brain permeability.
conclusionsCelastrol's efficacy on spasms is partially explained by its better brain penetration than edaravone's. NFkB inhibitors may be useful in treating drug-resistant IS but delivery methods with improved bioavailability and brain permeability are needed.
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