ArticleJournal of neuroinflammation2017
Everolimus is better than rapamycin in attenuating neuroinflammation in kainic acid-induced seizures.
Article in Journal of neuroinflammation, 2017. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 30 papers.
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Who cites it
30 citing papers in PubMed, 54 citations in OpenAlex.
- Review
- The NLRP3 Inflammasome in Neuropsychiatric Disorders: Molecular Mechanisms and Emerging Therapeutic Strategies.International journal of molecular sciences · 2026Review
- Research Prospects for mTOR in Neuroinflammation: A Bibliometric Analysis.CNS & neurological disorders drug targets · 2026Review
- Identifying brain-penetrant small-molecule modulators of human microglia using a cellular model of synaptic pruning.Neuropsychopharmacology : official publication of the American College of Neuropsychopharmacology · 2025Article
- Understanding the Molecular Basis of Miller-Dieker Syndrome.International journal of molecular sciences · 2025Review
- Inhibitory effects of the combination of rapamycin with gemcitabine plus paclitaxel on the growth of pancreatic cancer tumors.Human cell · 2025Article
- The Development of Methods of BLOTCHIPCurrent issues in molecular biology · 2025Review
- Experimental and clinical tests of FDA-approved kinase inhibitors for the treatment of neurological disorders (update 2024).Exploration of drug science · 2025Article
- Antiseizure Medications: Advancements, Challenges, and Prospects in Drug Development.Current neuropharmacology · 2025Review
- Development of patient-specific iPSC-based epilepsy models and identification of differentially expressed genes for disease mechanisms.Frontiers in neuroscience · 2025Article
- Innovative drug discovery strategies in epilepsy: integrating next-generation syndrome-specific mouse models to address pharmacoresistance and epileptogenesis.Expert opinion on drug discovery · 2024Review
- Pharmacological mTOR inhibitors in ameliorating Alzheimer's disease: current review and perspectives.Frontiers in pharmacology · 2024Review
- Berbamine suppresses intestinal SARS-CoV-2 infection via a BNIP3-dependent autophagy blockade.Emerging microbes & infections · 2023Article
- Tremor Induced by Cyclosporine, Tacrolimus, Sirolimus, or Everolimus: A Review of the Literature.Drugs in R&D · 2023Review
- Review
- The Neuroprotective Effects and Probable Mechanisms of Everolimus in a Rat Model of Intracerebral Hemorrhage.Cellular and molecular neurobiology · 2023Article
- Extension of microglial activation is associated with epilepsy and cognitive dysfunction in Tuberous sclerosis complex: A TSPO-PET study.NeuroImage. Clinical · 2023Article
- Neuroinflammation and status epilepticus: a narrative review unraveling a complex interplay.Frontiers in pediatrics · 2023Review
- FDA-Approved Kinase Inhibitors in Preclinical and Clinical Trials for Neurological Disorders.Pharmaceuticals (Basel, Switzerland) · 2022Review
- Rapamycin in Cerebral Cavernous Malformations: What Doses to Test in Mice and Humans.ACS pharmacology & translational science · 2022Review
Corrections and comments
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Authors and funding
5 authors at 4 institutions in 1 country.
Funding
No grant is acknowledged in the PubMed record.
Abstract
backgroundMicroglia is responsible for neuroinflammation, which may aggravate brain injury in diseases like epilepsy. Mammalian target of rapamycin (mTOR) kinase is related to microglial activation with subsequent neuroinflammation. In the present study, rapamycin and everolimus, both as mTOR inhibitors, were investigated in models of kainic acid (KA)-induced seizure and lipopolysaccharide (LPS)-induced neuroinflammation.
methodsIn vitro, we treated BV2 cells with KA and LPS. In vivo, KA was used to induce seizures on postnatal day 25 in B6.129P-Cx3cr1
resultsEverolimus was significantly more effective than rapamycin in inhibiting iNOS and mTOR signaling pathways in both models of neuroinflammation (LPS) and seizure (KA). Everolimus significantly attenuated the mRNA expression of iNOS by LPS and nitrite production by KA and LPS than that by rapamycin. Only everolimus attenuated the mRNA expression of mTOR by LPS and KA treatment. In the present study, we also found that the modulation of mTOR under LPS and KA treatment was not mediated by Akt pathway but was primarily mediated by ERK phosphorylation, which was more significantly attenuated by everolimus. This inhibition of ERK phosphorylation and microglial activation in the hippocampus by everolimus was also confirmed in KA-treated mice.
conclusionsRapamycin and everolimus can block the activation of inflammation-related molecules and attenuated the microglial activation. Everolimus had better efficacy than rapamycin, possibly mediated by the inhibition of ERK phosphorylation. Taken together, mTOR inhibitor can be a potential pharmacological target of anti-inflammation and seizure treatment.
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