A combination of drugs, electrical stimulation and treadmill exercises was used to reawaken 'walking circuits' in the spinal cords of paralysed rats

People who are left wheelchair-bound by spinal cord injuries could regain some of their mobility through a rehabilitation programme being developed by scientists. Guardian neuroscience stories have found that a combination of drugs, muscle stimulation and treadmill exercises helps paralysed rats to recover the ability to walk normally.

The animal tests pave the way for clinical trials in humans, which scientists hope to begin in the US and Switzerland within five years.

The treatment, developed by neurologists at the University of Zurich and the University of California in Los Angeles, taps into neural circuits in the spinal cord that control the muscles used for walking.

In able-bodied people, these "walking circuits" spring into action when they receive a signal from the brain, but if the spinal cord is damaged, the message from the brain never arrives. When contact with the brain is lost, the circuits shut down.

"We've known for more than a century that there are networks of neurons in the spinal cord that generate the rhythmic activity needed for walking," said Grégoire Courtine at the Experimental Neurorehabilitation laboratory in Zurich. "Our study suggests that the brain mostly sends a go or no-go signal."

A team led by Courtine used drugs known as serotonin agonists to awaken the walking circuits in paralysed rats whose spines had been severed. The researchers then used tiny electrodes to stimulate the animals' spinal circuitry, according to a report in the journal Nature Neuroscience.

During the eight-week study, the rats spent 20 minutes a day walking on a treadmill. At first they were unable to move their hind legs at all, but by the end of the study they could support their weight and walk almost perfectly. Although the rats had regained the ability to walk, they were still reliant on an electrical wire to switch their movements on and off.

Courtine said the group is eager to begin human trials, but first needs to develop implantable electrodes to stimulate the walking circuits in patients' spines.

"With a neuroprosthesis, we could get some improvement in function in patients with severe spinal cord injuries," he said. "The majority of patients have some intact spinal nerves that give them a limited ability to move their muscles. For these patients, our intervention could be extremely beneficial."

以老鼠为实验对象的研究发现，药物、电刺激与锻炼相结合的组合疗法，有助于唤醒瘫痪老鼠脊髓中受损的行走神经回路；这为瘫痪病人带来了新希望。

因脊髓损伤而坐轮椅的瘫痪病人可以通过科学家开发的一种康复方案重新获得一定程度的行动能力。《卫报》神经学栏目的报道新闻发现，联合使用药物、肌肉刺激及跑步机练习可以帮助瘫痪的老鼠重新恢复正常行走的能力。

动物实验的成功为相应的人类临床试验铺平了道路，科学家希望在五年内从美国和瑞士开始这种临床试验。

由苏黎世大学和加州大学洛杉矶分校的神经学专家开发的这种疗法所利用的就是脊髓中控制步行所用肌肉的神经回路。

对于健康的人来说，这些"行走回路"一旦收到大脑发出的信号之后，便迅速行动。但如果脊髓受到破坏，它们便无法获得大脑发出的讯息。当与大脑失去了联系，这些神经回路便会关闭。

"脊髓中含有产生行走所需节奏性活动的神经元网络，这一点早在一个多世纪前就为人所知了，"苏黎世实验神经康复实验室（Experimental Neurorehabilitation laboratory）的格雷瓜尔·库尔蒂纳（Grégoire Courtine）说，"我们的研究表明，大脑主要发送的是一个走或不走的信号。"

据刊登在《自然-神经学》（Nature Neuroscience）杂志上的一份报告所述，由库尔蒂纳带领的研究小组对脊髓完全受损的瘫痪老鼠进行了实验，实验中采用叫做血清素致效剂（serotonin agonist）的药物，来唤醒瘫痪老鼠的步行回路。接着，研究人员利用微型电极来刺激老鼠的脊髓回路。

在为期8周的研究中，老鼠每天在跑步机上行走20分钟。起初，它们根本无法移动后腿，但在研究结束时，这些老鼠可以承担全身的重量，而且可以近乎完美地步行。虽然这些老鼠已恢复了行走能力，但是，它们仍需依靠一根电线来带动自己行走及停止。

库尔蒂纳表示，该研究小组迫切希望开始人体试验，但首先需要开发便于刺激患者脊椎中步行回路的植入式电极。

"通过神经假体（neuroprosthesis）,我们可以使脊髓严重损伤的患者获得一些功能性改善，"他说，"大部分患者还有一些完好的脊髓神经，可以让他们能在有限范围内运用肌肉。对于这些患者来说，我们的疗法可能极有裨益。"