Electronic Facilitation of Functional Recovery Following CNS Trauma

博尔根斯9631560脊髓损伤对那些幸存下来的人来说是毁灭性的，会导致重要的身体功能终身丧失。功能丧失的部分原因是从脊髓到大脑的神经纤维断裂，以及从大脑到身体不同部位的神经纤维断裂。恢复这种“双向”脉冲传导的一种可能方法是诱导和引导损伤区域周围或穿过损伤区域的神经纤维再生。这种再生通常不会在哺乳动物中发生，但在其他脊椎动物中会自然发生，通常会导致脊髓损伤后的功能恢复。完成这一任务的一种新方法是在损伤部位施加弱电压。这种方法源于非常明确的证据，即施加电场既可以启动和指导纤维的生长；这一点已经在对培养中生长的神经细胞的研究中得到证明，以及在各种“全动物”研究中(例如，在原始鱼类和豚鼠的脊髓中)。神经突起向负极生长，并远离外加电压的正极而退化。微弱的外加电压也可能导致其他对损伤过程重要的细胞出现可预测的取向，如在脊髓中形成疤痕组织的星形胶质细胞和在急性损伤中也发挥突出作用的巨噬细胞。为了在临床上有用，施加的电压必须影响在脊髓内双向投射的神经过程。由于对负极的生长反应是立即的，而在正极发生的退化反应发生的时间要晚得多，所以可以每15到30分钟颠倒施加电压的方向，以在两个方向上产生神经生长。这称为振荡场刺激(OFS)。在兽医临床试验中，OFS已经在自然受伤的截瘫狗身上产生了显著的功能恢复水平。目前正在开发一种植入型OFS装置，用于人类患者的第一次试验；然而，在人类临床试验开始之前，必须收集更多关于OFS对其他哺乳动物的影响的信息。到目前为止，由于OFS装置的原型尺寸很大，涉及实验室大鼠和豚鼠的实验一直受到限制。在这项研究中，研究人员将使用最近开发的微型OFS设备，结合手持传感器从体外测试该单元的功能，以确定这项新技术的作用机制、靶细胞和关键方面。

Borgens 9631560 Spinal cord injuries are devastating to those that survive them, producing lifelong losses in important bodily functions. The loss of function is in part due to a break in the nerve fibers from the spinal cord to the brain, and those that carry impulses from the brain to various parts of the body. One possible means to restore this "two-way" impulse conduction is to induce and guide the regeneration of nerve fibers around or through the area of injury. Such regeneration does not normally happen in mammals, but occurs naturally in other vertebrates, usually leading to functional recovery after spinal cord injury. A novel means to accomplish this task is to impose a weak voltage across the injury site. This approach arises from very clear evidence that the application of this electrical field can both initiate and direct the growth of fibers; this has been shown in studies of nerve cells grown in culture, as well as in various "whole animal" studies (for example in the spinal cord of primitive fish and guinea pigs). Nerve processes grow towards the negative pole, and degenerate away from the positive pole of the applied voltage. Weak applied voltages may also induce a predictable orientation of other cells important to the injury process such as astrocytes, that form scar tissue in the spinal cord, and macrophages, which also play a prominent role in acute injury. To be clinically useful, an applied voltage must influence nerve processes projecting in both directions within the spinal cord. Since growth response towards the negative pole are immediate, and degenerative responses occurring at the positive pole occur much later, the direction of the applied voltage can be reversed every 15 to 30 minutes to produce nerve growth in both directions. This is called oscillating field stimulation (OFS). OFS has produced significant levels of functional recovery in naturally injured paraplegic dogs in veterinary clinical trials. An implantab le OFS unit is now in development for the first trial in human patients; however, before human clinical trials may begin, more information must be gathered on the effects of OFS in other mammals. Up to this point, experiments involving laboratory rats and guinea pigs have been limited due to the large size of the prototype OFS device. In this study, the investigators will use a recently developed miniaturized OFS device, combined with a hand-held sensor to test the function of the unit from outside the body, to determine the mechanisms of action, target cells and critical aspects of this new technology.