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

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作者
Xin-Tong Ge
Ping Lei
Hai-Chen Wang
An-Ling Zhang
Zhao-Li Han
Xin Chen
Sheng-Hui Li
Rong-Cai Jiang
Chun-Sheng Kang
Jian-Ning Zhang
机构
[1] Laboratory of Neuro-Trauma,Department of Neurosurgery
[2] Tianjin Neurological Institute,Department of Geriatrics
[3] Key Laboratory of Post-trauma Neuro-repair and Regeneration in Central Nervous System,Department of Neurology
[4] Ministry of Education,undefined
[5] Tianjin Medical University General Hospital,undefined
[6] Tianjin Medical University General Hospital,undefined
[7] Laboratory of Neuro-Trauma and Neurodegenerative Disorders,undefined
[8] Tianjin Geriatrics Institute,undefined
[9] Duke University School of Medicine,undefined
[10] Laboratory of Neuro-Oncology,undefined
[11] Tianjin Neurological Institute,undefined
[12] Tianjin Key Laboratory of Injuries,undefined
[13] Variations and Regeneration of Nervous System,undefined
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摘要
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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