The DOI matches its Crossref record; 79 of the 79 references it cites were found in a registry or an index.
An Antagomir to MicroRNA Let7f Promotes Neuroprotection in an Ischemic Stroke Model
Open accessAbstract
We previously showed that middle-aged female rats sustain a larger infarct following experimental stroke as compared to younger female rats, and paradoxically, estrogen treatment to the older group is neurotoxic. Plasma and brain insulin-like growth factor-1 (IGF-1) levels decrease with age. However, IGF-1 infusion following stroke, prevents estrogen neurotoxicity in middle-aged female rats. IGF1 is neuroprotective and well tolerated, but also has potentially undesirable side effects. We hypothesized that microRNAs (miRNAs) that target the IGF-1 signaling family for translation repression could be alternatively suppressed to promote IGF-1-like neuroprotection. Here, we report that two conserved IGF pathway regulatory microRNAs, Let7f and miR1, can be inhibited to mimic and even extend the neuroprotection afforded by IGF-1. Anti-mir1 treatment, as late as 4 hours following ischemia, significantly reduced cortical infarct volume in adult female rats, while anti-Let7 robustly reduced both cortical and striatal infarcts, and preserved sensorimotor function and interhemispheric neural integration. No neuroprotection was observed in animals treated with a brain specific miRNA unrelated to IGF-1 (anti-miR124). Remarkably, anti-Let7f was only effective in intact females but not males or ovariectomized females indicating that the gonadal steroid environment critically modifies miRNA action. Let7f is preferentially expressed in microglia in the ischemic hemisphere and confirmed in ex vivo cultures of microglia obtained from the cortex. While IGF-1 was undetectable in microglia harvested from the non-ischemic hemisphere, IGF-1 was expressed by microglia obtained from the ischemic cortex and was further elevated by anti-Let7f treatment. Collectively these data support a novel miRNA-based therapeutic strategy for neuroprotection following stroke.
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“Recently, miRNAs targeting several genes are involved in regulating microglia behavior and functions in diverse CNS pathologies including ischemic brain injuries (Selvamani et al., 2012; Zhao et al., 2013; Karthikeyan et al., 2018), multiple sclerosis (Ponomarev et al., 2011) and prion disease (Saba et al., 2012; Slota and Booth, 2019).”
From miR-142-3p Regulates BDNF Expression in Activated Rodent Microglia Through Its Target CAMK2A (2020) · cites this paper as Selvamani et al., 2012
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“Some in vitro and in vivo studies have shown the role of IGF-1 in promoting neuroprotection and neuroregeneration (Li et al., 2010; Selvamani et al., 2012; Sohrabji and Williams, 2013; Bake et al., 2014).”
From The impact of microglial activation on blood-brain barrier in brain diseases (2014) · cites this paper as Selvamani et al., 2012
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The Endothelial-Specific MicroRNA miR-126 Governs Vascular Integrity and Angiogenesis
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Paschon, V., Higa, G. S. V., Walter, L. T., de Sousa, É., Zuzarte, F. C. C., Weber, V. R. S., Resende, R. R., & Kihara, A. H. (2013) · PLoS ONE · doi:10.1371/annotation/4744b3c3-13a8-452d-9c59-5ca80c9614fe · Cited by 1
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Faculty Opinions recommendation of 40 YEARS of IGF1: IGF1: the Jekyll and Hyde of the aging brain.
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Additional file 1 of The aging ovary impairs acute stroke outcomes
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Park, K., Ahn, S. B., Oh, J., Park, J. Y., Lee, C., Kang, M., Lee, D. Y., & Lee, M. (2026) · Journal of Advanced Research · doi:10.1016/j.jare.2026.08.031
Metadata
- Authors
- Selvamani, A., Sathyan, P., Miranda, R. C., & Sohrabji, F.
- Affiliations
- Texas A&M Health Science Center (US)
- Corresponding author
- Sohrabji, Farida
- Venue
- PLoS ONE
- Publisher
- Public Library of Science (PLoS)
- Published
- 2012-02-29
- Volume
- 7
- Issue
- 2
- Pages
- e32662
- ISSN
- 1932-6203 (ISSN-L)
- PMC
- PMC3290559
- OpenAlex
- W2071432376
- Cited by
- 217
- References
- 79
- Citations by year
- 2026: 1 · 2025: 4 · 2024: 6 · 2023: 7 · 2022: 11 · 2021: 12 · 2020: 16 · 2019: 19 · 2018: 18 · 2017: 26 · 2016: 20 · 2015: 23 · 2014: 27 · 2013: 22 · 2012: 4
- FWCI
- 8.02
- Type
- journal article
- Language
- en
- Open access
- gold
- doi.org
- Locations
- PLoS ONE (publishedVersion, cc-by)
- Europe PMC (PubMed Central) (publishedVersion, cc-by)
- PubMed Central (publishedVersion, cc-by)
- PubMed (publishedVersion)
- DOAJ (DOAJ: Directory of Open Access Journals) (submittedVersion, cc-by-sa)
- Figshare (submittedVersion, cc-by)
- OakTrust (Texas A&M University Libraries) (submittedVersion)
- Funders
- National Institutes of Health
- National Institute on Aging (R01AG027684, AG027684, AG028303, R01AG028303)
- Topics
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Cancer Research › MicroRNA in disease regulation
- Life Sciences › Neuroscience › Neurology › Neuroinflammation and Neurodegeneration Mechanisms
- Health Sciences › Medicine › Clinical Neurology › Acute Ischemic Stroke Management
- Keywords
- ischemic stroke, neuroprotection, microRNA, let-7f, miR-1, insulin-like growth factor I, IGF-1 signaling, microglia, sex differences, infarct size, sensorimotor function, hemispheric integration, sex steroids
- MeSH terms
- Animals, Behavior, Animal, Disease Models, Animal, Female, Gene Expression Regulation, Insulin-Like Growth Factor I, Ischemia, Male, Sex Factors, Reperfusion Injury, Microglia, Neuroprotective Agents, Stroke, MicroRNAs, Rats
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