Ischemic stroke is a leading cause of irreversible brain damages and disabilities. In the past decade, much attention has been focused on exploring effective strategies to promote circuit reorganization and functional recovery post injury. Here, we showed that the expression level of a long non-coding RNA (lncRNA H19) is bilaterally increased in the sensorimotor cortex after a cerebral ischemia induced by middle cerebral artery occlusion (MCAO). Knock down of contralaterally elevated H19 robustly enhanced the midline-crossing sprouting of the intact corticospinal axons in the spinal cord. Furthermore, H19 knockdown mice showed significant improvement on the performance of the food pellet retrieval assay, a skilled, cortical dependent motor task. Mechanistically, lncRNA H19 inhibition increased IGF1R expression and activated IGF1 mediated mTOR pathway. Our research thereby provided novel insights into identifying therapeutic targets for ischemic stroke.
Keywords: Axon sprouting; Functional recovery; IGF1; Ischemic stroke; MCAO; lncRNA H19.
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