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MicroRNAs in the Blood-Brain Barrier in Hypoxic-Ischemic Brain Injury
1Department of Basic Sciences, The Lawrence D. Longo Center for Perinatal Biology, Loma Linda University School of Medicine, Loma Linda, CA 92350, United States.
Abstract:
Hypoxic-ischemic (HI) brain injury is a leading cause of acute mortality and chronic disability in newborns. Current evidence shows that cerebral microvascular response and compromised blood-brain barrier (BBB) integrity occur rapidly and could primarily be responsible for the brain injury observed in many infants with HI brain injury. MicroRNAs (miRNAs) are a type of highly conserved non-coding RNAs (ncRNAs), which consist of 21-25 nucleotides in length and usually lead to suppression of target gene expression. Growing evidence has revealed that brainenriched miRNAs act as versatile regulators of BBB dysfunctions in various neurological disorders including neonatal HI brain injury. In the present review, we summarize the current findings regarding the role of miRNAs in BBB impairment after hypoxia/ischemia brain injury. Specifically, we focus on the recent progress of miRNAs in the pathologies of neonatal HI brain injury. These findings can not only deepen our understanding of the role of miRNAs in BBB impairment in HI brain injury, but also provide insight into the development of new therapeutic strategies for preservation of BBB integrity under pathological conditions.
Insights
Hypoxic-ischemic brain injury in newborns involves rapid blood-brain barrier (BBB) damage. Brain-enriched microRNAs (miRNAs) are key regulators of this BBB dysfunction, offering therapeutic targets.
Area of Science:
- Neuroscience
- Molecular Biology
- Neonatal Medicine
Background:
- Neonatal hypoxic-ischemic (HI) brain injury is a major cause of infant mortality and disability.
- Cerebral microvascular responses and compromised blood-brain barrier (BBB) integrity are early events in HI brain injury.
- MicroRNAs (miRNAs), small non-coding RNAs, regulate gene expression and are implicated in neurological disorders.
Purpose of the Study:
- To review the current understanding of miRNAs' role in BBB impairment following hypoxia/ischemia.
- To highlight recent advancements in miRNAs' involvement in neonatal HI brain injury pathologies.
- To explore the potential of miRNAs as therapeutic targets for preserving BBB integrity.
Main Methods:
- Literature review synthesizing current findings on miRNAs and BBB function in HI brain injury.
- Focus on brain-enriched miRNAs and their regulatory mechanisms in neonatal HI contexts.
- Analysis of recent research on miRNA involvement in the pathophysiology of neonatal HI brain injury.
Main Results:
- Brain-enriched miRNAs are identified as critical regulators of BBB integrity.
- Specific miRNAs contribute to BBB dysfunction in neonatal HI brain injury.
- Dysregulation of miRNAs exacerbates neurological damage post-hypoxia/ischemia.
Conclusions:
- miRNAs play a significant role in BBB impairment after HI brain injury.
- Understanding miRNA mechanisms provides insights into neonatal HI brain injury.
- Targeting miRNAs may offer novel therapeutic strategies for protecting the BBB.
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