Micro Ribonucleic Acid (miRNA) Markers of Hydrocephalus in Intraventricular Hemorrhage (IVH)

IVH is an important cause of brain injury in newborns and more so in those born prematurely. Depending on the severity of the hemorrhage and the care provided the newborn, the impact of IVH can range from a temporary issue with no permanent consequences to a life-threatening condition with severe neurodevelopmental sequelae. The outcomes of patients with IVH are not only dictated by the direct effects of the hemorrhage, but to associated processes such as hydrocephalus, periventricular infarction and leukomalacia. Despite the availability of better diagnostic and therapeutic tools, the incidence of IVH has remained constant over the past 50 years, and is mostly due to the increased survival rates of very low weight premature infants. Recent statistics demonstrate that close to 12,000 premature infants develop IVH in the United 'states every year and more than 50% of them develop some degree of posthemorrhagic hydrocephalus (PHH). It is believed that PHH originates as a result or arachnoiditis, gliosis, and subsequent fibrosis impairing the flow and reabsorption of cerebrospinal fluid (CSF). Despite the lack of clarity about the pathogenesis of PHH, it is well accepted that its presence exacerbates the damage caused by the hemorrhage to the periventricular white matter. Multiple efforts have been made to identify the mechanisms and mediators of the development of PHH and white matter damage. Molecules such as transforming growth factor-beta (TGF-beta) have been demonstrated to enhance the expression of genes encoding for fibronectin, collagen and other extracellular matrix components. Unfortunately, not enough evidence has been generated to be able to envision a potential solution for the problem. The current management of PHH is focused on controlling the damage that pressure, distortion, and/or ischemia may cause to the immature brain. Direct evacuation of ventricular contents with CSF diversion mechanisms remains, such as sequential lumber punctures, external ventricular draining, and reservoir placement. Intraventricular fibrinolytic therapy or permanent shunting represent most effective tools by mechanically evacuating bleeding products and preventing the accumulation of CSF. However, they are all highly invasive techniques that carry major risks and complications. The use of diuretics has been presented as a non-invasive alternative, but the results prove them inefficient. Extracellular miRNA sequences have been found to be major modulators of protein coding genes involved in differentiation, proliferation, and apoptosis. Several studies have reported the presence of significant amounts of miRNA in extracellular fluids such as plasma, urine, saliva, and semen. The researchers believe that extracellular miRNAs are present in CSF and that sequential evaluation of their expression can provide a unique biomarker signature, time sensitive enough to reflect the evolution of pathological events underlying the development of PHH. The identification of a miRNA biomarker for PHH development and/or hemorrhagic related injury would also be a means to quickly evaluate treatment response.