miRNA PC-5P-12969 expression levels in patients with acute ischemic stroke confirmed by intracranial imaging and a matched control group.
Clinical Neurology; Neurosurgery and Neuroradiology
Final Report Abstract
Cerebrovascular diseases, which include strokes, are the second most common cause of death worldwide after cardiovascular diseases. It is also the leading cause of serious long-term disability worldwide.1 Stroke is divided into ischemic stroke and intracranial hemorrhage (intracerebral hemorrhage, subarachnoid hemorrhage). Ischemic stroke, which is caused by occlusion of one or more intracranial vessels, is the most common entity, accounting for 87% of cases. In the acute phase ischemic stroke can be detected by means of clinical examination and diagnostic imaging using computed tomography or magnetic resonance imaging (MRI) whereas MRI represents the gold standard. However, MRI can be false-negative in up to 8% of cases if performed within 48 hours of the onset of symptoms. It is also important to note that patients with stroke can only be treated with intravenous lysis therapy in the first 4.5 hours after the onset of stroke. However, in certain situations, patients may also benefit from treatment with endovascular therapy within 24 hours and/or systemic thrombolysis within the extended time window of 9 hours. Therefore, research has attempted to establish biomarkers that may be supportive in the acute phase. In recent years, it has been shown that protein-based biomarkers do not lead to a sufficient improvement in diagnostic accuracy. The focus has increasingly shifted with the development of genetic test methods that detect the smallest changes in ribonucleic acids (RNA). Messenger RNA (mRNA) and microRNA (miRNA) based biomarkers are particularly noteworthy. In particular, the miRNA PC-5P-12969 was shown to have high specificity for acute stroke in the mouse model as well as in a small human cohort. MicroRNAs are a class of small (~19-24 nucleotides) endogenous and evolutionarily conserved RNAs that serve as post-transcriptional regulators of gene expression and messenger RNA (mRNA) degradation by modulating the expression of target mRNAs. MiRNAs play an important key role in cell differentiation, growth, mobility, and programmed cell death. Thus, miRNAs represent one of the first changes after stroke and might serve as immediate biomarkers that can provide useful information for further treatment for stroke patients in the treatment window. A fast and accurate diagnosis, which may be possible with the help of miRNAs, could shorten the time to start treatment, with the result that mortality and an improvement of potential consequences of a delayed stroke treatment can be minimized. The project submitted by the applicant aims to determine whether patients with acute ischaemic stroke are characterized by an increased expression of the miRNA PC-5p-12969 compared to matched controls.
