Ghali Michael George Zaki, Marchenko Vitaliy
Department of Neurobiology and Anatomy, Drexel University College of Medicine , Philadelphia, Pennsylvania.
J Neurotrauma. 2016 Jun 15;33(12):1115-27. doi: 10.1089/neu.2015.4034. Epub 2015 Oct 23.
Studies conducted since the second half of the 19th century have revealed spontaneous as well as pharmacologically induced phasic/rhythmic discharge in spinal respiratory motor outputs of cats, dogs, rabbits, and neonatal rats following high cervical transection (Tx). The extent to which these various studies validate the existence of a true spinal respiratory rhythm generator remains debated. In this set of studies, we seek to characterize patterns of spontaneous phasic/rhythmic, asphyxia-induced, and pharmacologically induced activity occurring in phrenic nerve (PhN) discharge after complete high cervical (C1-C2) spinal cord transection. Experiments were performed on 20 unanesthetized decerebrate Sprague-Dawley adult male rats. Patterns of spontaneous activity after spinalization included tonic, phasic, slow oscillatory, and long-lasting tonic discharges. Topical application of antagonists of GABAA and glycine receptors to C1- and C2- spinal segments induced left-right synchronized phasic decrementing activity in PhN discharge that was abolished by an additional C2Tx. Asphyxia elicited increases in tonic activity and left-right synchronized gasp-like bursts in PhN discharge, demonstrating the presence of spinal circuits that may underlie a spinal gasping-like mechanism. We conclude that intrinsic slow oscillators and a phasic burst/rhythm generator exist in the spinal cord of the adult rat. If present in humans, this mechanism may be exploited to recover respiratory function in patients sustaining severe spinal cord injury.
自19世纪下半叶以来开展的研究表明,在猫、狗、兔子和新生大鼠经高颈段横断(Tx)后的脊髓呼吸运动输出中,存在自发性以及药理学诱导的相位性/节律性放电。这些不同研究在多大程度上证实了真正的脊髓呼吸节律发生器的存在仍存在争议。在这组研究中,我们试图描述在完全性高颈段(C1-C2)脊髓横断后膈神经(PhN)放电中出现的自发性相位性/节律性、窒息诱导性和药理学诱导性活动的模式。实验在20只未麻醉的去大脑成年雄性Sprague-Dawley大鼠身上进行。脊髓横断后的自发性活动模式包括紧张性、相位性、缓慢振荡性和持续性紧张性放电。向C1和C2脊髓节段局部应用GABAA和甘氨酸受体拮抗剂,可诱导膈神经放电出现左右同步的相位性递减活动,额外进行C2横断可消除这种活动。窒息可引起膈神经放电中紧张性活动增加以及左右同步的喘息样爆发,表明存在可能构成脊髓喘息样机制基础的脊髓回路。我们得出结论,成年大鼠脊髓中存在内在的慢振荡器和相位性爆发/节律发生器。如果人类也存在这种机制,那么在严重脊髓损伤患者中,或许可以利用该机制来恢复呼吸功能。