Paz Amaya J, Marchionne F, Krupka A J, Duong T, Lemay M A
Department of Bioengineering, Temple University, 1947 N 12th St, Philadelphia, PA 19122, United States of America.
College of Sciences, DeSales University, 2755 Station Ave, Center Valley, PA 18034, United States of America.
J Neural Eng. 2025 Feb 21;22(1). doi: 10.1088/1741-2552/adb0f3.
In the present study, we examined the correlations between the recovery of stepping obtained with intrathecal brain derived neurotrophic factor (BDNF) delivery to the lumbar spinal cord and the firing of the lumbar spinal interneurons in a feline model of spinal cord injury (SCI).extracellular recordings of spinal neurons were conducted using two 64-channel microelectrode arrays inserted in the intermediate zone of the L3-L7 segments of cats spinalized at the T11-T12 level that received either saline or BDNF delivered intrathecally to the lumbar cisterna via an implanted minipump. Interneuronal activity was explored in terms of averaged neuronal firing properties and in terms of spike train interactions.With respect to averaged neuronal firing properties, we observed a significant increase in firing frequency in BNDF-treated animals and a similar distribution of the units' preferred phase of firing relative to the step cycle between the groups. With respect to spike train interactions, we observed higher synchrony of firing in BDNF-treated animals as well as less dependency on the unit's past firing.Studies conducted in feline models of complete SCI show a gradual recovery of hindlimb stepping after intensive treadmill training. Similarly, delivery of neurotrophins such as BDNF or neurotrophin-3 to the injury site via cellular transplant or via implantable mini-pump to the lumbar cisterna has been shown to promote recovery of locomotor behavior in the absence of locomotor training. The results from this study suggest that BDNF treatment sets the overall population in a state of high excitability, which along with higher synchrony and ensemble-dependent behavior, allows for the proper integration of cutaneous and proprioceptive input resulting in treadmill locomotor recovery after SCI.
在本研究中，我们在脊髓损伤（SCI）猫模型中，研究了经鞘内注射脑源性神经营养因子（BDNF）至腰脊髓所获得的踏步恢复与腰脊髓中间神经元放电之间的相关性。使用两个64通道微电极阵列对脊髓神经元进行细胞外记录，这些阵列插入在T11 - T12水平脊髓横断的猫的L3 - L7节段的中间带，通过植入的微型泵将生理盐水或BDNF经鞘内注射至腰大池。从平均神经元放电特性以及放电序列相互作用方面探究中间神经元的活动。关于平均神经元放电特性，我们观察到BDNF治疗组动物的放电频率显著增加，且两组之间单位放电的偏好相位相对于步周期的分布相似。关于放电序列相互作用，我们观察到BDNF治疗组动物的放电同步性更高，且对单位过去放电的依赖性更小。在完全性SCI猫模型中进行的研究表明，经过强化跑步机训练后后肢踏步逐渐恢复。同样，通过细胞移植或经植入微型泵将BDNF或神经营养因子-3等神经营养素输送至损伤部位，已显示在无运动训练的情况下可促进运动行为的恢复。本研究结果表明，BDNF治疗使总体神经元处于高兴奋性状态，这与更高的同步性和群体依赖性行为一起，使得皮肤和本体感觉输入得以适当整合，从而导致SCI后跑步机运动恢复。
