University of Miami, Miami, FL 33136, USA.
Neurorehabil Neural Repair. 2012 May;26(4):374-84. doi: 10.1177/1545968311425178. Epub 2011 Dec 19.
. Brainstem regions with descending axons could influence recovery after spinal cord injury, thus presenting potential targets for treatment. Neurons in the hindbrain raphe magnus respond to sensory and chemical concomitants of trauma (eg, pain, circulating cytokines) and release trophic substances (serotonin, neuropeptides) in widespread spinal regions.
. The authors tested in rats whether intermittent stimulation of the raphe magnus or its major midbrain input, the periaqueductal gray, influences recovery from incomplete thoracic (T8) injury.
. After a moderate weight-drop injury, an implanted wireless stimulator intermittently delivered cathodal pulses (8 Hz, 30 µA) through a microelectrode for 12 hours daily over multiple days. Stimulators in controls were inactive or not implanted.
. Raphe magnus stimulation, started 1 to 2 hours after injury, enduringly improved open-field motor performance (measured weekly for 8 weeks) and footprint and gridwalk performance (measured in the 9th week). These improvements increased with days of stimulation (1-7). Myelinated axons in perilesional white matter and serotonin-containing terminals in gray matter, quantified 14 weeks postinjury, also increased. In separate parametric studies that examined open-field behavior following 14 days of stimulation, starting 2 days after injury was better than 7 days or 2 hours; starting at 8 weeks appeared ineffective. The periaqueductal gray, an established, safe stimulation target in man, similarly facilitated recovery of motor performance and myelination (but not serotonergic terminals) when stimulated for 4 to 7 days.
. Raphe magnus neurons mediate restorative feedback in acute spinal cord injury. Their interim activation, direct or indirect (via periaqueductal gray), offers a basis for possible treatments in patients.
具有下行轴突的脑干区域可能会影响脊髓损伤后的恢复，因此成为治疗的潜在靶点。后脑中缝大核的神经元对创伤的感觉和化学伴随物（例如疼痛、循环细胞因子）做出反应，并在广泛的脊髓区域释放营养物质（血清素、神经肽）。
作者在大鼠中测试了中缝大核或其主要中脑输入，即导水管周围灰质的间歇性刺激是否会影响不完全性胸 8 损伤的恢复。
在中度重物坠落伤后，植入的无线刺激器通过微电极每天间歇地传递 12 小时的阴极脉冲（8 Hz，30 µA），持续多天。对照中的刺激器处于非活动状态或未植入。
中缝大核刺激在损伤后 1 至 2 小时开始，持久地改善了旷场运动表现（每周测量 8 周）和足迹和网格行走表现（在第 9 周测量）。这些改善随刺激天数的增加而增加（1-7 天）。损伤后 14 周测量的损伤区周围白质中的有髓轴突和灰质中的含血清素终末也增加了。在单独的参数研究中，在损伤后 14 天开始刺激 14 天后，开始刺激 2 天比 7 天或 2 小时更好；8 周后开始刺激似乎无效。导水管周围灰质是一种已确立的、在人类中安全的刺激靶点，当刺激 4 至 7 天时，同样可以促进运动表现和髓鞘形成（但不能促进血清素能终末）的恢复。
中缝大核神经元在急性脊髓损伤中介导修复性反馈。它们的临时激活，无论是直接还是间接（通过导水管周围灰质），为患者的可能治疗提供了基础。
