Heaton James T, Sheu Shu Hsien, Hohman Marc H, Knox Christopher J, Weinberg Julie S, Kleiss Ingrid J, Hadlock Tessa A
Department of Surgery, Massachusetts General Hospital, Harvard Medical School, 55 Fruit Street, Boston, MA 02114, United States.
Department of Pathology, Brigham and Women's Hospital, Harvard Medical School, 75 Francis Street, Boston, MA 02114, United States.
Neuroscience. 2014 Apr 18;265:9-20. doi: 10.1016/j.neuroscience.2014.01.038. Epub 2014 Jan 28.
Vibrissal whisking is often employed to track facial nerve regeneration in rats; however, we have observed similar degrees of whisking recovery after facial nerve transection with or without repair. We hypothesized that the source of non-facial nerve-mediated whisker movement after chronic denervation was from autonomic, cholinergic axons traveling within the infraorbital branch of the trigeminal nerve (ION). Rats underwent unilateral facial nerve transection with repair (N=7) or resection without repair (N=11). Post-operative whisking amplitude was measured weekly across 10weeks, and during intraoperative stimulation of the ION and facial nerves at ⩾18weeks. Whisking was also measured after subsequent ION transection (N=6) or pharmacologic blocking of the autonomic ganglia using hexamethonium (N=3), and after snout cooling intended to elicit a vasodilation reflex (N=3). Whisking recovered more quickly and with greater amplitude in rats that underwent facial nerve repair compared to resection (P<0.05), but individual rats overlapped in whisking amplitude across both groups. In the resected rats, non-facial-nerve-mediated whisking was elicited by electrical stimulation of the ION, temporarily diminished following hexamethonium injection, abolished by transection of the ION, and rapidly and significantly (P<0.05) increased by snout cooling. Moreover, fibrillation-related whisker movements decreased in all rats during the initial recovery period (indicative of reinnervation), but re-appeared in the resected rats after undergoing ION transection (indicative of motor denervation). Cholinergic, parasympathetic axons traveling within the ION innervate whisker pad vasculature, and immunohistochemistry for vasoactive intestinal peptide revealed these axons branching extensively over whisker pad muscles and contacting neuromuscular junctions after facial nerve resection. This study provides the first behavioral and anatomical evidence of spontaneous autonomic innervation of skeletal muscle after motor nerve lesion, which not only has implications for interpreting facial nerve reinnervation results, but also calls into question whether autonomic-mediated innervation of striated muscle occurs naturally in other forms of neuropathy.
触须摆动常被用于追踪大鼠面神经的再生；然而，我们观察到，在面神经切断后无论是否进行修复，触须摆动恢复的程度相似。我们推测，慢性去神经支配后非面神经介导的触须运动源于自主胆碱能轴突，这些轴突在三叉神经眶下支（ION）内走行。大鼠接受单侧面神经切断并修复（N = 7）或切断且不修复（N = 11）。术后每周测量触须摆动幅度，持续10周，并在⩾18周时术中刺激ION和面神经。在随后切断ION（N = 6）或使用六甲铵对自主神经节进行药理学阻断（N = 3）后，以及在旨在引发血管舒张反射的口鼻冷却后（N = 3），也测量触须摆动。与切断组相比，接受面神经修复的大鼠触须摆动恢复得更快且幅度更大（P<0.05），但两组中个体大鼠的触须摆动幅度有重叠。在切断组大鼠中，ION的电刺激可引发非面神经介导的触须摆动，注射六甲铵后暂时减弱，ION切断后消失，口鼻冷却后迅速且显著增加（P<0.05）。此外，在初始恢复期，所有大鼠中与颤动相关的触须运动均减少（表明再支配），但在切断ION后，切断组大鼠中又重新出现（表明运动去神经支配）。ION内走行的胆碱能、副交感轴突支配触须垫血管，血管活性肠肽免疫组织化学显示，这些轴突在面神经切断后在触须垫肌肉上广泛分支并接触神经肌肉接头。本研究提供了运动神经损伤后骨骼肌自发自主神经支配的首个行为学和解剖学证据，这不仅对解释面神经再支配结果有意义，也对其他形式的神经病变中是否自然发生自主神经介导的横纹肌支配提出了质疑。
