Intranasal Delivery of miR-155-5p Antagomir Alleviates Acute Seizures Likely by Inhibiting Hippocampal Inflammation
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INTRODUCTION: To confront the resistance to existing antiepileptic drugs, studies have gradually begun to investigate alternative pathologies distinct from the traditional treatments that overwhelmingly target ion channels. Microglia activation is the first inflammatory response in the brain, in which miR-155-5p plays a key proinflammatory role and thus represents a promising target for inflammatory modulation in epilepsy pathologies. METHODS: In this study, a pentetrazol-induced acute seizure model was established, and the seizure degree was evaluated within 60 min after pentetrazol administration. Animals were then sacrificed for hippocampal tissue collection for biological experiments. RESULTS: Intranasal delivery of miR-155-5p antagomir (30 min before pentetrazol administration) increased the percentage of animals with no induced seizures by 20%, extended the latency to generalized convulsions, and decreased seizure severity. In addition, miR-155-5p antagomir treatment alleviated hippocampal damage and decreased the expression of typical inflammatory modulators (TNF-α, IL-1β and IL-6). Further research revealed that intranasal delivery of miR-155-5p antagomir significantly decreased the relative level of miR-155-5p and increased the expression of its targets LXRα and SOCS1 in IBA1-labeled microglial cells in the hippocampus. CONCLUSION: These findings demonstrate that intranasal delivery of miR-155-5p antagomir alleviated acute seizures, likely by blocking hippocampal inflammation. However, other potential mechanisms of the effects of miR-155-5p antagomir and its long-term safety for epilepsy treatment remain to be investigated.
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Intranasal delivery of an miR-155-5p antagomir alleviated acute seizures by countering hippocampal inflammation in a pentetrazol-induced model.
“while intranasal delivery of an miR-155-5p antagomir alleviated acute seizures by countering hippocampal inflammation in pentetrazol-induced model [62].”
From Microglia specific deletion of miR-155 in Alzheimer’s disease mouse models reduces amyloid-β pathology but causes hyperexcitability and seizures (2023) · cites this paper as [62]
The Results report reduced seizure severity and inflammatory markers after intranasal antagomir delivery in the pentetrazol-induced model. The Discussion and Conclusion say blocking hippocampal inflammation was the likely mechanism, whereas the citing sentence presents that causal explanation without the qualification. (LLM, conf=0.88)
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The molecular basis of JAK/STAT inhibition by SOCS1
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Aloi, M. S., Prater, K. E., Sánchez, R. E. A., Beck, A., Pathan, J. L., Davidson, S., Wilson, A., Keene, C. D., de la Iglesia, H., Jayadev, S., et al. (2023) · Journal of Neuroinflammation · doi:10.1186/s12974-023-02745-6 · Cited by 43 · see citing works
- Authors
- Zhou, X., Chen, J., Tao, H., Cai, Y., Huang, L., Zhou, H., Chen, Y., Cui, L., Zhong, W., & Li, K.
- Affiliations
- Guangdong Medical College (CN)
- Jinan University (CN)
- Corresponding author
- Tao, Hua
- Venue
- Neuropsychiatric Disease and Treatment
- Publisher
- Informa UK Limited
- Published
- 2020-05
- Volume
- Volume 16
- Pages
- 1295-1307
- ISSN
- 1176-6328 (ISSN-L)
- 1178-2021
- PMC
- PMC7251485
- OpenAlex
- W3026540416
- Cited by
- 26
- References
- 2
- Citations by year
- 2026: 2 · 2025: 5 · 2024: 8 · 2023: 6 · 2022: 3 · 2021: 1 · 2020: 1
- FWCI
- 2.01
- Type
- journal article
- Language
- en
- Open access
- gold
- doi.org
- Licence
- Locations
- Neuropsychiatric Disease and Treatment (publishedVersion, cc-by-nc)
- PubMed Central (publishedVersion, cc-by-nc)
- PubMed (publishedVersion)
- Dove Medical Press (Taylor and Francis Group) (submittedVersion, cc-by-nc)
- Funders
- Natural Science Foundation of Guangdong Province (2017A030310658)
- Guangdong Medical Research Foundation (A2019152)
- Topics
- Health Sciences › Medicine › Psychiatry and Mental health › Epilepsy research and treatment
- Life Sciences › Neuroscience › Neurology › Neuroinflammation and Neurodegeneration Mechanisms
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Cancer Research › MicroRNA in disease regulation
- Keywords
- miR-155-5p, antagomir, intranasal drug delivery, acute seizures, epilepsy, hippocampal inflammation, microglial activation, liver X receptor alpha, SOCS1, TNF-α, IL-1β, interleukin-6, antiepileptic drug resistance
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