ArticleEpilepsia2021
Antiepileptogenic effects of rapamycin in a model of infantile spasms due to structural lesions.
Article in Epilepsia, 2021. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 11 papers.
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Who cites it
11 citing papers in PubMed, 16 citations in OpenAlex.
- The multiple hit model of infantile and epileptic spasms: The 2025 update.Epilepsia open · 2025Article
- Absence seizures: Update on signaling mechanisms and networks.Epilepsia open · 2025Article
- Experimental and clinical tests of FDA-approved kinase inhibitors for the treatment of neurological disorders (update 2024).Exploration of drug science · 2025Article
- Efficacy and tolerability of celastrol and edaravone in the multiple-hit rat model of infantile spasms.Epilepsy & behavior : E&B · 2025Article
- Early preclinical plasma protein biomarkers of brain trauma are influenced by early seizures and levetiracetam.Epilepsia open · 2023Article
- Cortical Parvalbumin-Positive Interneuron Development and Function Are Altered in the APC Conditional Knockout Mouse Model of Infantile and Epileptic Spasms Syndrome.The Journal of neuroscience : the official journal of the Society for Neuroscience · 2023Article
- Involvement of orexin type-2 receptors in genetic absence epilepsy rats.Frontiers in neurology · 2023Article
- Developmental and epileptic encephalopathies: from genetic heterogeneity to phenotypic continuum.Physiological reviews · 2023Review
- FDA-Approved Kinase Inhibitors in Preclinical and Clinical Trials for Neurological Disorders.Pharmaceuticals (Basel, Switzerland) · 2022Review
- Molecular Mechanism of Overcoming Host Resistance by theMicroorganisms · 2022Article
- Vigabatrin-associated brain abnormalities on MRI in tuberous sclerosis complex patients with infantile spasms: are they preventable?Therapeutic advances in neurological disorders · 2022Article
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Authors and funding
5 authors at 3 institutions in 2 countries.
Funding
Abstract
objectiveInfantile spasms may evolve into persistent epilepsies including Lennox-Gastaut syndrome. We compared adult epilepsy outcomes in models of infantile spasms due to structural etiology (multiple-hit model) or focal cortical inflammation and determined the anti-epileptogenic effects of pulse-rapamycin, previously shown to stop spasms in multiple-hit rats.
methodsSpasms were induced in 3-day-old male rats via right intracerebral doxorubicin/lipopolysaccharide (multiple-hit model) infusions. Controls and sham rats were used. Separate multiple-hit rats received pulse-rapamycin or vehicle intraperitoneally between postnatal days 4 and 6. In adult mice, video-EEG (electroencephalography) scoring for seizures and sleep and histology were done blinded to treatment.
resultsMotor-type seizures developed in 66.7% of multiple-hit rats, usually from sleep, but were reduced in the pulse-rapamycin-treated group (20%, p = .043 vs multiple-hit) and rare in other groups (0-9.1%, p < .05 vs multiple-hit). Spike-and-wave bursts had a slower frequency in multiple-hit rats (5.4-5.8Hz) than in the other groups (7.6-8.3Hz) (p < .05); pulse rapamycin had no effect on the hourly spike-and-wave burst rates in adulthood. Rapamycin, however, reduced the time spent in slow-wave-sleep (17.2%), which was increased in multiple-hit rats (71.6%, p = .003). Sham rats spent more time in wakefulness (43.7%) compared to controls (30.6%, p = .043). Multiple-hit rats, with or without rapamycin treatment, had right more than left corticohippocampal, basal ganglia lesions. There was no macroscopic pathology in the other groups. SIGNIFICANCE: Structural corticohippocampal/basal ganglia lesions increase the risk for post-infantile spasms epilepsy, Lennox-Gastaut syndrome features, and sleep dysregulation. Pulse rapamycin treatment for infantile spasms has anti-epileptogenic effects, despite the structural lesions, and decreases the time spent in slow wave sleep.
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