Article

miR-21 improves the neurological outcome after traumatic brain injury in rats

Xintong Ge1] Laboratory of Neuro-Trauma, Tianjin Neurological Institute, Tianjin, China [2] Key Laboratory of Post-trauma Neuro-repair and Regeneration in Central Nervous System, Ministry of Education, Tianjin, China; Tianjin Key Laboratory of Injuries, Variations and Regeneration of Nervous System, Tianjin, Tianjin, China [3] Department of Neurosurgery, Tianjin Medical University General Hospital, Tianjin, ChinaPing Lei1] Key Laboratory of Post-trauma Neuro-repair and Regeneration in Central Nervous System, Ministry of Education, Tianjin, China; Tianjin Key Laboratory of Injuries, Variations and Regeneration of Nervous System, Tianjin, Tianjin, China [2] Department of Neurosurgery, Tianjin Medical University General Hospital, Tianjin, China [3] Department of Geriatrics, Tianjin Medical University General Hospital, Tianjin, China; Laboratory of Neuro-Trauma and Neurodegenerative Disorders, Tianjin Geriatrics Institute, Tianjin, ChinaHaichen WangDepartment of Neurology, Duke University School of Medicine, Durham, North Carolina, U.S.AAnling Zhang1] Key Laboratory of Post-trauma Neuro-repair and Regeneration in Central Nervous System, Ministry of Education, Tianjin, China; Tianjin Key Laboratory of Injuries, Variations and Regeneration of Nervous System, Tianjin, Tianjin, China [2] Department of Neurosurgery, Tianjin Medical University General Hospital, Tianjin, China [3] Laboratory of Neuro-Oncology, Tianjin Neurological Institute, Tianjin, ChinaZhaoli Han1] Laboratory of Neuro-Trauma, Tianjin Neurological Institute, Tianjin, China [2] Key Laboratory of Post-trauma Neuro-repair and Regeneration in Central Nervous System, Ministry of Education, Tianjin, China; Tianjin Key Laboratory of Injuries, Variations and Regeneration of Nervous System, Tianjin, Tianjin, China [3] Department of Geriatrics, Tianjin Medical University General Hospital, Tianjin, China; Laboratory of Neuro-Trauma and Neurodegenerative Disorders, Tianjin Geriatrics Institute, Tianjin, ChinaXin Chen1] Laboratory of Neuro-Trauma, Tianjin Neurological Institute, Tianjin, China [2] Key Laboratory of Post-trauma Neuro-repair and Regeneration in Central Nervous System, Ministry of Education, Tianjin, China; Tianjin Key Laboratory of Injuries, Variations and Regeneration of Nervous System, Tianjin, Tianjin, China [3] Department of Neurosurgery, Tianjin Medical University General Hospital, Tianjin, ChinaShenghui Li1] Laboratory of Neuro-Trauma, Tianjin Neurological Institute, Tianjin, China [2] Key Laboratory of Post-trauma Neuro-repair and Regeneration in Central Nervous System, Ministry of Education, Tianjin, China; Tianjin Key Laboratory of Injuries, Variations and Regeneration of Nervous System, Tianjin, Tianjin, China [3] Department of Neurosurgery, Tianjin Medical University General Hospital, Tianjin, ChinaRongcai Jiang1] Laboratory of Neuro-Trauma, Tianjin Neurological Institute, Tianjin, China [2] Key Laboratory of Post-trauma Neuro-repair and Regeneration in Central Nervous System, Ministry of Education, Tianjin, China; Tianjin Key Laboratory of Injuries, Variations and Regeneration of Nervous System, Tianjin, Tianjin, China [3] Department of Neurosurgery, Tianjin Medical University General Hospital, Tianjin, ChinaChunsheng Kang1] Key Laboratory of Post-trauma Neuro-repair and Regeneration in Central Nervous System, Ministry of Education, Tianjin, China; Tianjin Key Laboratory of Injuries, Variations and Regeneration of Nervous System, Tianjin, Tianjin, China [2] Department of Neurosurgery, Tianjin Medical University General Hospital, Tianjin, China [3] Laboratory of Neuro-Oncology, Tianjin Neurological Institute, Tianjin, ChinaJianning Zhang1] Laboratory of Neuro-Trauma, Tianjin Neurological Institute, Tianjin, China [2] Key Laboratory of Post-trauma Neuro-repair and Regeneration in Central Nervous System, Ministry of Education, Tianjin, China; Tianjin Key Laboratory of Injuries, Variations and Regeneration of Nervous System, Tianjin, Tianjin, China [3] Department of Neurosurgery, Tianjin Medical University General Hospital, Tianjin, China

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Abstract

The expression levels of microRNAs (miRNAs) including miR-21, have been reported to change in response to traumatic brain injury (TBI), suggesting that they may influence the pathophysiological process in brain injury. To analyze the potential effect of miR-21 on neurological function after TBI, we employed the fluid percussion injury rat model and manipulated the expression level of miR-21 in brain using intracerebroventricular infusion of miR-21 agomir or antagomir. We found that upregulation of miR-21 level in brain conferred a better neurological outcome after TBI by improving long-term neurological function, alleviating brain edema and decreasing lesion volume. To further investigate the mechanism underlying this protective effect, we evaluated the impact of miR-21 on apoptosis and angiogenesis in brain after TBI. We found that miR-21 inhibited apoptosis and promoted angiogenesis through regulating the expression of apoptosis- and angiogenesis-related molecules. In addition, the expression of PTEN, a miR-21 target gene, was inhibited and Akt signaling was activated in the procedure. Taken together, these data indicate that miR-21 could be a potential therapeutic target for interventions after TBI.

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DOI: 10.1038/srep06718

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