Yu James Young Ho, Chen Thomas C, Danilov Camelia A
Department of Neurological Surgery, University of Southern California, 1200 N State St., Suite 3300, Los Angeles, CA 90033, USA.
Department of Neurological Surgery, University of Southern California, 2011 Zonal Ave., Los Angeles, CA 90089, USA.
Int J Mol Sci. 2024 Mar 6;25(5):3058. doi: 10.3390/ijms25053058.
Our previous research studies have demonstrated the role of microRNA133b (miR133b) in healing the contused spinal cord when administered either intranasally or intravenously 24 h following an injury. While our data showed beneficial effects of exogenous miR133b delivered within hours of a spinal cord injury (SCI), the kinetics of endogenous miR133b levels in the contused spinal cord and rostral/caudal segments of the injury were not fully investigated. In this study, we examined the miR133b dysregulation in a mouse model of moderate unilateral contusion injury at the fifth cervical (C5) level. Between 30 min and 7 days post-injury, mice were euthanized and tissues were collected from different areas of the spinal cord, ipsilateral and contralateral prefrontal motor cortices, and off-targets such as lung and spleen. The endogenous level of miR133b was determined by RT-qPCR. We found that after SCI, (a) most changes in miR133b level were restricted to the injured area with very limited alterations in the rostral and caudal parts relative to the injury site, (b) acute changes in the endogenous levels were predominantly specific to the lesion site with delayed miR133b changes in the motor cortex, and (c) ipsilateral and contralateral hemispheres responded differently to unilateral SCI. Our results suggest that the therapeutic window for exogenous miR133b therapy begins earlier than 24 h post-injury and potentially lasts longer than 7 days.
我们之前的研究表明，在脊髓损伤后24小时经鼻或静脉给予微小RNA133b（miR133b）可促进脊髓挫伤的愈合。虽然我们的数据显示在脊髓损伤（SCI）数小时内给予外源性miR133b具有有益效果，但对于挫伤脊髓及其损伤头端/尾端节段内源性miR133b水平的动力学变化尚未进行充分研究。在本研究中，我们在第五颈椎（C5）水平的中度单侧挫伤损伤小鼠模型中检测了miR133b的失调情况。在损伤后30分钟至7天之间，对小鼠实施安乐死，并从脊髓的不同区域、同侧和对侧前额叶运动皮层以及肺和脾等非靶向组织收集样本。通过逆转录定量聚合酶链反应（RT-qPCR）测定miR133b的内源性水平。我们发现，脊髓损伤后：（a）miR133b水平的大多数变化局限于损伤区域，相对于损伤部位，其头端和尾端部分的变化非常有限；（b）内源性水平的急性变化主要局限于损伤部位，而运动皮层中miR133b的变化出现延迟；（c）同侧和对侧半球对单侧脊髓损伤的反应不同。我们的结果表明，外源性miR133b治疗的治疗窗口始于损伤后24小时之前，并且可能持续超过7天。
