引用

在C2前外侧脊髓索单侧横断脊髓半切后，膈肌节律性活动逐渐恢复。脑源性神经营养因子(BDNF)通过其全长原肌凝蛋白相关激酶受体亚型B (TrkB.FL)作用于脊髓损伤后的神经可塑性，但具体的细胞底物尚不清楚。我们假设选择性靶向增加TrkB。FL对膈运动神经元的表达足以增强SH后膈节律性活动的恢复。我们筛选了几种表达GFP的腺相关病毒(AAV)血清型，以确定成年大鼠胸膜内注射膈运动神经元转导的特异性。在AAV血清型7、8和9治疗3周后，颈脊髓中存在GFP表达，但AAV2、6或恒河河-10治疗3周后不存在GFP表达。总的来说，AAV7在膈肌运动神经元中产生了最一致的GFP表达。胸膜内注射表达人TrkB的AAV7后3周行SH。FL-FLAG或生理盐水。TrkB的交付。fll -FLAG在膈肌运动细胞核和人TrkB中的表达证实了fll -FLAG作用于膈肌运动神经元。微解剖膈肌运动神经元中FL mRNA的表达。在所有SH大鼠中，在SH后3天，同侧膈肌肌电图活动消失，证实对膈肌运动神经元的同侧下降驱动完全中断。 At 14 days post-SH, all AAV7-TrkB.FL treated rats (n=11) displayed recovery of ipsilateral diaphragm EMG activity compared to 3 out of 8 untreated SH rats (p<0.01). During eupnea, AAV7-TrkB.FL treated rats exhibited 737% of pre-SH root mean squared EMG vs. only 3111% in untreated SH rats displaying recovery (p<0.01). This study provides direct evidence that increased TrkB.FL expression in phrenic motoneurons is sufficient to enhance recovery of ipsilateral rhythmic phrenic activity after SH, indicating that selectively targeting gene expression in spared motoneurons below the level of spinal cord injury may promote functional recovery.