Department of Physiology and Biomedical Engineering, Mayo Clinic, Rochester, Minnesota.
Department of Anesthesiology and Perioperative Medicine, Mayo Clinic, Rochester, Minnesota.
J Neurophysiol. 2021 Jun 1;125(6):2158-2165. doi: 10.1152/jn.00146.2021. Epub 2021 May 5.
Unilateral C hemisection (CSH) disrupts descending inspiratory-related drive to phrenic motor neurons and thus, silences rhythmic diaphragm muscle (DIAm) activity. There is gradual recovery of rhythmic DIAm EMG activity over time post-CSH, consistent with neuroplasticity, which is enhanced by chronic (2 wk) intrathecal BDNF treatment. In the present study, we hypothesized that acute (30 min) intrathecal BDNF treatment also enhances recovery of DIAm EMG activity after CSH. Rats were implanted with bilateral DIAm EMG electrodes to verify the absence of ipsilateral eupneic DIAm EMG activity at the time of CSH and at 3 days post-CSH. In those animals displaying no recovery of DIAm EMG activity after 28 days ( = 7), BDNF was administered intrathecally (450 mcg) at C. DIAm EMG activity was measured continuously both before and for 30 min after BDNF treatment, during eupnea, hypoxia-hypercapnia, and spontaneous sighs. Acute BDNF treatment restored eupneic DIAm EMG activity in all treated animals to an amplitude that was 78% ± 9% of pre-CSH root mean square (RMS) ( < 0.001). In addition, acute BDNF treatment increased DIAm RMS EMG amplitude during hypoxia-hypercapnia ( = 0.023) but had no effect on RMS EMG amplitude during sighs. These results support an acute modulatory role of BDNF signaling on excitatory synaptic transmission at phrenic motor neurons after cervical spinal cord injury. Brain-derived neurotrophic factor (BDNF) plays an important role in promoting neuroplasticity following unilateral C spinal hemisection (CSH). BDNF was administered intrathecally in rats displaying lack of ipsilateral inspiratory-related diaphragm (DIAm) EMG activity after CSH. Acute BDNF treatment (30 min) restored eupneic DIAm EMG activity in all treated animals to 78% ± 9% of pre-CSH level. In addition, acute BDNF treatment increased DIAm EMG amplitude during hypoxia-hypercapnia but had no effect on EMG amplitude during sighs.
单侧半横切（CSH）破坏了膈神经运动神经元的吸气相关驱动，从而使膈肌（DIAm）的节律性活动沉默。CSH 后，随着神经可塑性的增强，DIAm 的肌电图（EMG）活动逐渐恢复，这种恢复可持续 2 周的鞘内 BDNF 治疗。在本研究中，我们假设急性（30 分钟）鞘内 BDNF 治疗也能增强 CSH 后 DIAm EMG 活动的恢复。大鼠双侧膈神经 EMG 电极植入以验证 CSH 时和 CSH 后 3 天同侧无吸气性 DIAm EMG 活动。在那些 28 天（=7）后 DIAm EMG 活动没有恢复的动物中，BDNF 被鞘内给予（450mcg）。BDNF 治疗前后，在呼吸、低氧高碳酸血症和自发性叹息期间，连续测量 DIAm EMG 活动。急性 BDNF 治疗使所有治疗动物的呼吸性 DIAm EMG 活动恢复到 CSH 前均方根（RMS）的 78%±9%（<0.001）。此外，急性 BDNF 治疗增加了低氧高碳酸血症时 DIAm RMS EMG 振幅（=0.023），但对叹息时 RMS EMG 振幅没有影响。这些结果支持 BDNF 信号在颈脊髓损伤后对膈神经运动神经元兴奋性突触传递的急性调节作用。脑源性神经营养因子（BDNF）在单侧 C 脊髓半横切（CSH）后促进神经可塑性中起着重要作用。CSH 后，在同侧吸气相关膈肌（DIAm）EMG 活动缺失的大鼠中鞘内给予 BDNF。急性 BDNF 治疗（30 分钟）使所有治疗动物的呼吸性 DIAm EMG 活动恢复到 CSH 前水平的 78%±9%。此外，急性 BDNF 治疗增加了低氧高碳酸血症时 DIAm EMG 振幅，但对叹息时 EMG 振幅没有影响。
