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Keywords: microRNA, cerebral ischemia, middle cerebral artery occlusion, biomarker, therapeutic agent/target, miR-320a
Issue Date: 22-Nov-2012
Citation: LIM KAI YING (2012-11-22). MICRORNAS IN CEREBRAL ISCHEMIA. ScholarBank@NUS Repository.
Abstract: Cerebral ischemia, also known as stroke, is a debilitating condition caused by the reduction of blood flow to the brain. The impact of stroke can be seen in individuals by the sudden onset of clinical symptoms such as numbness in the limbs or altered speech patterns. Severe cases can even result in death. Although stroke diagnosis is often aided by complex imaging techniques, they are never specific or accurate enough. This is further complicated by the time-limited efficacy of recombinant plasminogen activator, the only approved thrombolytic drug. Over the years, foremost effort has been placed on the search for stroke specific biomarkers that would aid the clinicians in the diagnosis and prognosis of patients as well as in finding suitable neuroprotectant(s) to contain the damage to the brain tissue. Nevertheless success has been limited. As the progression of stroke (ischemic cascade), induces various biochemical changes in the cellular systems, this study, explored the changes in microRNAs for potential biomarkers which could reflect the ischemic pathophysiology accurately and also attempted to use them as neuroprotectant(s). microRNAs are small non-coding RNA molecules that are capable of either activating or silencing the expression of functional genes. Thus this study explored the regulatory potential of microRNAs to reduce or reverse the damages mediated by the ischemic cascade. Using animal models with middle cerebral artery occlusion, we identified several microRNAs as possible biomarkers of acute stroke. miR-320a was found to show potential as a therapeutic target as well. More importantly, anti miR-320a was found to be a potential neuroprotectant which was also able to prolong the time-limited efficacy of recombinant plasminogen activator. Regulating miR-320a expression was found to be beneficial in the treatment of cerebral ischemia.
Appears in Collections:Ph.D Theses (Open)

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