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Remote Limb Ischemic Preconditioning: A Neuroprotective Technique in Rodents
Published on: June 2, 2015
MicroRNAs induced during ischemic preconditioning
Soon-Tae Lee1, Kon Chu, Keun-Hwa Jung
1Department of Neurology, Clinical Research Institute, Seoul National University Hospital, Seoul, South Korea.
Background And Purpose:
MicroRNAs (miRNA) are single-stranded short RNA molecules that regulate gene expression by either degradation or translational repression of mRNA. Although miRNAs control a number of conditions and diseases, few neuroprotective miRNAs have been described. In this study, we investigated neuroprotective miRNAs induced early in ischemic preconditioning.
Methods:
Ischemic preconditioning or focal cerebral ischemia was induced in mice by transient occlusion of the middle cerebral artery for 15 or 120 minutes. We prepared RNA samples from the ischemic cortex at 3 or 24 hours after the onset of ischemia. Selective miRNAs then were synthesized and transfected into Neuro-2a cells before oxygen-glucose deprivation.
Results:
We detected a total of 360 miRNAs. Two miRNA families, miR-200 and miR-182, were selectively upregulated at 3 hours after ischemic preconditioning. Transfections of some of these were neuroprotective in in vitro ischemia. Among them, miR-200b, miR-200c, and miR-429 targeted prolyl hydroxylase 2 and had the best neuroprotective effect.
Conclusions:
Two miRNA families, miR-200 and miR-182, were upregulated early after ischemic preconditioning and the miR-200 family was neuroprotective mainly by downregulating prolyl hydroxylase 2 levels. These miRNAs may be useful in future research and therapeutic applications.
Insights
Early after ischemic preconditioning, specific microRNAs (miRNAs) like the miR-200 family were upregulated. These neuroprotective miRNAs, particularly miR-200b, miR-200c, and miR-429, show promise for stroke research and therapy.
Area of Science:
- Molecular Biology
- Neuroscience
- Genetics
Background:
- MicroRNAs (miRNAs) are key regulators of gene expression.
- Few neuroprotective miRNAs have been identified.
- Understanding early miRNA changes in brain ischemia is crucial.
Purpose of the Study:
- To identify neuroprotective miRNAs induced by early ischemic preconditioning.
- To investigate the role of specific miRNAs in protecting against stroke-related damage.
Main Methods:
- Focal cerebral ischemia was induced in mice.
- RNA was extracted from the ischemic cortex at 3 and 24 hours post-ischemia.
- Selected miRNAs were transfected into Neuro-2a cells for in vitro testing.
Main Results:
- 360 miRNAs were detected; miR-200 and miR-182 families were upregulated early (3 hours).
- miR-200b, miR-200c, and miR-429 demonstrated significant neuroprotection in vitro.
- These miRNAs target prolyl hydroxylase 2, mediating their protective effect.
Conclusions:
- The miR-200 and miR-182 families are upregulated early following ischemic preconditioning.
- The miR-200 family confers neuroprotection, primarily by downregulating prolyl hydroxylase 2.
- These identified miRNAs hold potential for future therapeutic strategies in stroke treatment.

