Studies on repairing of hemisected thoracic spinal cord of adult rats by using a chitosan tube filled with alginate fibers

A chitosan tube filled with alginate fibers was implanted into the injured spinal cord of a rat for repairing the damaged tissue. Twelve months after the operation, the morphological observation demonstrated that this chitosan tube could induce regeneration of myelinated and non-myelinated axons and blood vessels. The Basso-Beattie-Bresnahan (BBB) behavioral evaluation confirmed that the implants played a key role in the long-term restoration of rats motor functions. It is a promising start in the treatment of the patients with the injury of the spinal cord.     

Restoration of grasp following paralysis through brain-controlled stimulation of muscles

Patients with spinal cord injury lack the connections between brain and spinal cord circuits that are essential for voluntary movement. Clinical systems that achieve muscle contraction through functional electrical stimulation (FES) have proven to be effective in allowing patients with tetraplegia to regain control of hand movements and to achieve a greater measure of independence in daily activities. In existing clinical systems, the patient uses residual proximal limb movements to trigger pre-programmed stimulation that causes the paralysed muscles to contract, allowing use of one or two basic grasps. Instead, we have developed an FES system in primates that is controlled by recordings made from microelectrodes permanently implanted in the brain. We simulated some of the effects of the paralysis caused by C5 or C6 spinal cord injury by injecting rhesus monkeys with a local anaesthetic to block the median and ulnar nerves at the elbow. Then, using recordings from approximately 100 neurons in the motor cortex, we predicted the intended activity of several of the paralysed muscles, and used these predictions to control the intensity of stimulation of the same muscles. This process essentially bypassed the spinal cord, restoring to the monkeys voluntary control of their paralysed muscles. This achievement is a major advance towards similar restoration of hand function in human patients through brain-controlled FES. We anticipate that in human patients, this neuroprosthesis would allow much more flexible and dexterous use of the hand than is possible with existing FES systems.     

Neuronal ensemble control of prosthetic devices by a human with tetraplegia

Neuromotor prostheses (NMPs) aim to replace or restore lost motor functions in paralysed humans by routeing movement-related signals from the brain, around damaged parts of the nervous system, to external effectors. To translate preclinical results from intact animals to a clinically useful NMP, movement signals must persist in cortex after spinal cord injury and be engaged by movement intent when sensory inputs and limb movement are long absent. Furthermore, NMPs would require that intention-driven neuronal activity be converted into a control signal that enables useful tasks. Here we show initial results for a tetraplegic human (MN) using a pilot NMP. Neuronal ensemble activity recorded through a 96-microelectrode array implanted in primary motor cortex demonstrated that intended hand motion modulates cortical spiking patterns three years after spinal cord injury. Decoders were created, providing a 'neural cursor' with which MN opened simulated e-mail and operated devices such as a television, even while conversing. Furthermore, MN used neural control to open and close a prosthetic hand, and perform rudimentary actions with a multi-jointed robotic arm. These early results suggest that NMPs based upon intracortical neuronal ensemble spiking activity could provide a valuable new neurotechnology to restore independence for humans with paralysis.     

大鼠SNL神经性疼痛模型的建立

摘要:目的　建立大鼠L5和L6脊神经结扎(Spinal nerve ligation,SNL)疼痛模型并进行评价, 方法　根据大鼠痛阈值测定结果,选择90只符合要求的SD雄性大鼠进行手术操作,术后每隔1d测定大鼠后足的机械痛阈值,比较术前和术后大鼠对疼痛刺激的反应变化。 结果　术后大鼠左足的痛阈值逐渐降低,至10d 后趋于稳定,与术前有明显差异(P≤0.01);右足的痛阈值微有升高,保持在稳定的水平内。 结论　本研究建立的大鼠SNL模型机械痛阈变化明显,稳定性好,可靠性高,可以作为大鼠一种神经病理性疼痛的模型。     

Direct control of paralysed muscles by cortical neurons

A potential treatment for paralysis resulting from spinal cord injury is to route control signals from the brain around the injury by artificial connections. Such signals could then control electrical stimulation of muscles, thereby restoring volitional movement to paralysed limbs. In previously separate experiments, activity of motor cortex neurons related to actual or imagined movements has been used to control computer cursors and robotic arms, and paralysed muscles have been activated by functional electrical stimulation. Here we show that Macaca nemestrina monkeys can directly control stimulation of muscles using the activity of neurons in the motor cortex, thereby restoring goal-directed movements to a transiently paralysed arm. Moreover, neurons could control functional stimulation equally well regardless of any previous association to movement, a finding that considerably expands the source of control signals for brain-machine interfaces. Monkeys learned to use these artificial connections from cortical cells to muscles to generate bidirectional wrist torques, and controlled multiple neuron-muscle pairs simultaneously. Such direct transforms from cortical activity to muscle stimulation could be implemented by autonomous electronic circuitry, creating a relatively natural neuroprosthesis. These results are the first demonstration that direct artificial connections between cortical cells and muscles can compensate for interrupted physiological pathways and restore volitional control of movement to paralysed limbs.     

Reach and grasp by people with tetraplegia using a neurally controlled robotic arm

Paralysis following spinal cord injury, brainstem stroke, amyotrophic lateral sclerosis and other disorders can disconnect the brain from the body, eliminating the ability to perform volitional movements. A neural interface system could restore mobility and independence for people with paralysis by translating neuronal activity directly into control signals for assistive devices. We have previously shown that people with long-standing tetraplegia can use a neural interface system to move and click a computer cursor and to control physical devices. Able-bodied monkeys have used a neural interface system to control a robotic arm, but it is unknown whether people with profound upper extremity paralysis or limb loss could use cortical neuronal ensemble signals to direct useful arm actions. Here we demonstrate the ability of two people with long-standing tetraplegia to use neural interface system-based control of a robotic arm to perform three-dimensional reach and grasp movements. Participants controlled the arm and hand over a broad space without explicit training, using signals decoded from a small, local population of motor cortex (MI) neurons recorded from a 96-channel microelectrode array. One of the study participants, implanted with the sensor 5?years earlier, also used a robotic arm to drink coffee from a bottle. Although robotic reach and grasp actions were not as fast or accurate as those of an able-bodied person, our results demonstrate the feasibility for people with tetraplegia, years after injury to the central nervous system, to recreate useful multidimensional control of complex devices directly from a small sample of neural signals.     

大鼠坐骨神经切断后经皮低频高强度电刺激相应脊髓节段中GAP-43表达的变化

目的探讨成年Wister大鼠在坐骨神经切断后GAP-43于相应脊髓节段前角运动神经元内的表达变化.方法选取健康成年雄性Wister大鼠60只,将坐骨神经切断,随机分为实验组和对照组,实验组给予经皮低频高强度电刺激,分别于术后1,2,4,8,12,16周处死,取其L4~L6脊髓,利用免疫组织化学技术检测GAP-43在相应脊髓节段中的表达变化,并利用影像分析系统进行统计学分析.结果对照组:1周时前角细胞胞体内GAP-43有明显表达,4周时达到高峰,5~8周时逐渐下调,9~16周时GAP-43在前角细胞胞体内中仍有少量表达,并呈弱阳性.实验组:1周时前角细胞胞体内GAP-43有明显表达,2周时达到高峰,且在4~16周时在神经元中仍有表达,并呈阳性.结论坐骨神经切断可导致成年大鼠相应脊髓节段中前角运动神经元GAP-43表达明显增加,可证明在周围神经损伤后神经元的再生能力增强,但时效很短.而给予低频高强度电刺激疗法后,GAP-43的表达在时长和量上都有明显增加.     

兔膝关节骨关节炎模型建立的探讨

摘要: 目的 探讨应用前交叉韧带和内外侧半月板切除的方法制作骨关节炎( OA) 动物模型的可行性及可靠性。 方法 成年雄性新西兰大白兔 20 只,于右后肢膝关节切断前交叉韧带和切除内外侧半月板,左后肢仅打开关节 囊,不对关节内部进行操作,观察术后兔子活动情况; 于第 2、6、10 周处死,观察其左、右两侧后肢膝关节软骨病理 改变。实验动物 2、6、10 周后取右后肢膝关节软骨为实验组,左侧肢体膝关节软骨标本为对照组,比较两组软骨病 变情况。结果 2、6、10 周后,从实验动物活动表现和大体标本观察,兔右后肢膝关节均呈典型的 OA 特征。结论 前交叉韧带和内外侧半月板切除是一个制作 OA 动物模型的较为理想的方法。     

大鼠脊髓楔型半切空洞模型的建立及评估

摘要: 目的建立一种新型大鼠脊髓半切模型,为临床脊髓空洞损伤研究提供适宜的动物模型。方法25 只SD 大鼠随机分为脊髓楔型块状半切组( A 组,n = 10) 、假手术组( B 组,n = 10) 和正常对照组( C 组,n = 5) 。术后采用 BBB 运动功能评分、斜板试验、HE 染色和核磁共振( MRI) 检测综合评价脊髓半切模型的稳定性。结果术后A 组 大鼠伤侧后肢BBB 运动功能评分及斜板维持最大角度值显著低于B 组和C 组( P ＜ 0. 05) ,而这些指标在B 组和C 组之间没有明显差异; 术后28 d HE 和MRI 检测显示脊髓损伤区( A 组) 灰质和白质发生明显的形态学改变。结论 通过该方法建立的脊髓半切模型稳定、可靠,适于脊髓空洞性损伤的研究。     

FPGA多通道视皮层刺激器

设计了一款用于视皮层视觉修复的基于FPGA的多通道视皮层刺激器。该刺激器由FPGA和外围电压/电流转换电路两部分组成。FPGA内部包括刺激脉冲发生器和多个多路选择器:刺激脉冲发生器产生各种形式的脉冲序列信号;多路选择器作为控制端实现对信号的选择,每一通道对应一个多路选择器,增加多路选择器即可实现通道的增加。FPGA输出的电压信号通过外围电压/电流转换电路,转换为电流信号后传入电极阵列。采用Altera公司Cyclone系列EP1C6型FPGA制作了四通道实验样机进行动物实验。采用猫作为实验对象,在猫的视皮层硬脑膜外左右两侧植入微电极,左侧接入刺激信号,右侧记录脑电,实验结果显示,视皮层能够响应来自对硬脑膜的电刺激,验证了所设计的刺激器是可行的。     

Relation of neurons in the nonprimary motor cortex to bilateral hand movement

In the primate cerebral cortex there are at least two somatotopically organized, nonprimary motor fields rostral to the primary motor area. To understand the functions of these multiple motor representations we have compared the neuronal activity in each of these fields while monkeys performed a trained motor task, using right, left or both hands. In the nonprimary motor cortex, activity in a number of neurons was related to the movement the animal chose and performed, whereas in the primary motor cortex, changes in the firing of most neurons were simply related to activity in the contralateral muscles. This result indicates that the nonprimary motor cortex is involved in higher-order coding of the laterality of the motor response, implying that it exerts its motor control function at a higher hierarchical level than its counterpart in the primary motor cortex.     

Functional brain laterality for sequential movements： Impact of transient practice

The impact of learning on brain functional laterality has not been systematically investigated. We employed an event-related functional magnetic resonance imaging combined with a delayed sequential movement task to investigate brain activation pattern and laterality during a transient practice in 12 subjects. Both hemispheres, involving motor areas and posterior parietal cortex, were engaged during motor preparation and execution, with larger activation volume in the left hemisphere than in the right. Activation volume in these regions significantly decreased after a transient practice, with more reduction in the right hemisphere resulting increase in left lateralization. The theoretical implications of these findings are discussed in relation to the physiological significance of brain functional laterality.     

基于图论算法的脊髓损伤后大脑皮层运动区神经元网络分析

 脊髓损伤(SCI)后大脑皮层运动区神经元的功能重组对机体功能康复的影响仍然不为人知。脊髓损伤前后,对一只在跑步机上直立行走的恒河猴的大脑皮层运动区神经元信号进行记录,利用不同神经元动作电位序列间的相关系数建立神经元网络图。为了研究神经元活动模式的变化与功能康复之间的联系,利用图论算法计算了神经元网络图的全局效能指标和神经元脆弱性指标。结果显示,不同时期神经元活动模式的显著变化意味着运动区神经元的功能重组(神经可塑性)与脊髓损伤后猴子的功能康复状态紧密相关,且这种神经功能重组对于猴子步行功能的康复起了非常重要的积极作用。     

基于触觉P300的脑控下肢康复机器人

基于P300信号的脑机接口技术在康复医疗领域具有广阔的应用前景,但P300信号的诱发方式多为视听刺激诱发,容易导致患者视听疲劳,同时也限制了视听障碍患者的使用。针对这些不足,设计一种基于触觉P300的脑控下肢康复机器人系统,在被试的左右食指处各放置一个振动器,通过调整左右手振动器的刺激间隔、刺激时长及刺激比例让P300信号更容易诱发和区分;利用共空间模式算法和支持向量机对信号进行特征提取和分类。被试通过选择关注左手或右手的振动刺激输出不同指令,从而控制下肢康复机器人进行相应动作。实验证明,被试通过感受振动刺激可以轻松诱发脑电中的P300信号,在不进行P300信号平均叠加的条件下,分类准确率为86.50%,既保证了较高的分类准确率,又缩短了指令输出时间。每位被试均可通过下肢康复系统顺利完成训练任务,证明了该方法的可行性。     

Spontaneous and evoked activity of fetal primary afferents in vivo

The first movements of the fetus are apparently random and spontaneous. Their onset coincides with the growth of dorsal root afferents into the spinal cord and it is possible that they are not simply a result of spontaneous motoneuron activity but are reflex responses to sensory stimulation. It is not clear what stimuli could normally evoke such reflexes because nothing is known of the properties of primary afferent neurons in the fetus. I have investigated this by making recordings from single dorsal root ganglion cells in fetal rats in vivo. The afferents have small, defined receptive fields and respond to mechanical stimulation of skin or muscle at intensities that might occur in utero. Many of them are also chemosensitive. Unlike postnatal afferents they display background activity which peaks at the same age as fetal movements. Repeated stimulation causes long-lasting increases of both background and evoked activity. Such sensory input is likely to have a considerable influence on fetal movements and on the development of spinal cord connections.     

Functional regeneration of respiratory pathways after spinal cord injury

Spinal cord injuries often occur at the cervical level above the phrenic motor pools, which innervate the diaphragm. The effects of impaired breathing are a leading cause of death from spinal cord injuries, underscoring the importance of developing strategies to restore respiratory activity. Here we show that, after cervical spinal cord injury, the expression of chondroitin sulphate proteoglycans (CSPGs) associated with the perineuronal net (PNN) is upregulated around the phrenic motor neurons. Digestion of these potently inhibitory extracellular matrix molecules with chondroitinase ABC (denoted ChABC) could, by itself, promote the plasticity of tracts that were spared and restore limited activity to the paralysed diaphragm. However, when combined with a peripheral nerve autograft, ChABC treatment resulted in lengthy regeneration of serotonin-containing axons and other bulbospinal fibres and remarkable recovery of diaphragmatic function. After recovery and initial transection of the graft bridge, there was an unusual, overall increase in tonic electromyographic activity of the diaphragm, suggesting that considerable remodelling of the spinal cord circuitry occurs after regeneration. This increase was followed by complete elimination of the restored activity, proving that regeneration is crucial for the return of function. Overall, these experiments present a way to markedly restore the function of a single muscle after debilitating trauma to the central nervous system, through both promoting the plasticity of spared tracts and regenerating essential pathways.     

成人四肢长骨的非对称性

本文测量了乌鲁木齐地区出土的200副成年四肢长骨。在左、右两侧长度相差大于0.1厘米时,四肢六骨(男性腓骨除外)均以非对称性为主。若以肱骨+桡骨、股骨+胫骨长作为上、下肢长,则右上肢与左下肢占优势,上、下肢单侧优势呈交叉关系。 在左右侧重量相差大于1％时,四肢六骨不论男女也均以非对称性为主,其中上肢以右大于左的占先势,而下肢也以右大于左的居多,在重量上看不出上、下肢单侧优势呈交叉关系。     

Development of an invasive brain machine interface with a monkey model

Brain-machine interfaces (BMIs) translate neural activities of the brain into specific instructions that can be carried out by external devices. BMIs have the potential to restore or augment motor functions of paralyzed patients suffering from spinal cord damage. The neural activities have been used to predict the 2D or 3D movement trajectory of monkey’s arm or hand in many studies. However, there are few studies on decoding the wrist movement from neural activities in center-out paradigm. The present study developed an invasive BMI system with a monkey model using a 10×10-microelectrode array in the primary motor cortex. The monkey was trained to perform a two-dimensional forelimb wrist movement paradigm where neural activities and movement signals were simultaneous recorded. Results showed that neuronal firing rates highly correlated with forelimb wrist movement; > 70% (105/149) neurons exhibited specific firing changes during movement and > 36% (54/149) neurons were used to discriminate directional pairs. The neuronal firing rates were also used to predict the wrist moving directions and continuous trajectories of the forelimb wrist. The four directions could be classified with 96% accuracy using a support vector machine, and the correlation coefficients of trajectory prediction using a general regression neural network were above 0.8 for both horizontal and vertical directions. Results showed that this BMI system could predict monkey wrist movements in high accuracy through the use of neuronal firing information.     

Dissociation between hand motion and population vectors from neural activity in motor cortex

The population vector hypothesis was introduced almost twenty years ago to illustrate that a population vector constructed from neural activity in primary motor cortex (MI) of non-human primates could predict the direction of hand movement during reaching. Alternative explanations for this population signal have been suggested but could not be tested experimentally owing to movement complexity in the standard reaching model. We re-examined this issue by recording the activity of neurons in contralateral MI of monkeys while they made reaching movements with their right arms oriented in the horizontal plane-where the mechanics of limb motion are measurable and anisotropic. Here we found systematic biases between the population vector and the direction of hand movement. These errors were attributed to a non-uniform distribution of preferred directions of neurons and the non-uniformity covaried with peak joint power at the shoulder and elbow. These observations contradict the population vector hypothesis and show that non-human primates are capable of generating reaching movements to spatial targets even though population vectors based on MI activity do not point in the direction of hand motion.     

A VIP-containing system concentrated in the lumbosacral region of human spinal cord

Neuropeptides were first localized in the human spinal cord by immunocytochemistry and substance P has been shown, by the same method, to be reduced ipsilaterally in the dorsal horn after limb amputation and bilaterally in the Riley-Day syndrome. Several neuropeptides increasingly fulfil the criteria to establish them as neurotransmitters or neuromodulators, and they may also have trophic actions in the spinal cord. Using radioimmunoassay and immunocytochemistry, we present here for the first time a quantitative regional distribution and localization of vasoactive intestinal polypeptide (VIP), substance P, somatostatin, bombesin and cholecystokinin (CCK-8) in normal postmortem human spinal cord. A comparison of the distribution of these peptides reveals an exceptional pattern for VIP, with relatively much higher levels in the lumbosacral region. Immunocytochemical analysis shows a distinctive distribution of VIP-containing fibres and terminals at the lumbosacral segments. This VIP-containing system may have an important role in the spinal control of urogenital function in man.