MicroRNA therapeutic targets in neonatal hypoxic-ischemic brain injury: a narrative review

Abstract

Neonatal hypoxic-ischemic brain injury (HIBI) is a devastating injury resulting from impaired blood flow and oxygen delivery to the brain at or around the time of birth. Despite the use of therapeutic hypothermia, more than one in four survivors suffer from major developmental disabilities-an indication of the critical need for more effective therapies. MicroRNAs (miRNA) have the potential to act as biomarkers and/or therapeutic targets in neonatal HIBI as a step toward improving outcomes in this high-risk population. This review summarizes the current literature around the use of cord blood and postnatal circulating blood miRNA expression for diagnosis or prognosis in human infants with hypoxic-ischemic encephalopathy, as well as animal studies assessing endogenous brain miRNA expression and potential for therapeutic targeting of miRNA expression for neuroprotection. Ultimately, the lack of knowledge regarding brain specificity of circulating miRNAs and the temporal variability in expression currently limit the use of miRNAs as biomarkers. However, given their broad effect profile, ease of administration, and small size allowing for effective blood-brain barrier crossing, miRNAs represent promising therapeutic targets for improving brain injury and reducing developmental impairments in neonates after HIBI. IMPACT: The high morbidity and mortality of neonatal hypoxic-ischemic brain injury (HIBI) despite current therapies demonstrates a need for developing more sensitive biomarkers and superior therapeutic options. MicroRNAs have been evaluated both as biomarkers and therapeutic options after neonatal HIBI. The limited knowledge regarding brain specificity of circulating microRNAs and temporal variability in expression currently limit the use of microRNAs as biomarkers. Future studies comparing the neuroprotective effects of modulating microRNA expression must consider temporal changes in the endogenous expression to determine appropriate timing of therapy, while also optimizing techniques for delivery.