BEHAVIORAL AND ANATOMICAL STUDIES OF SPINAL CORD DAMAGE

脊髓损伤的行为和解剖学研究

• 批准号: 3414560
• 负责人: MICHAEL E GOLDBERGER
• 金额: $ 12.45万
• 依托单位: ALLEGHENY UNIVERSITY OF HEALTH SCIENCES
• 依托单位国家: 美国
• 财政年份: 1990
• 资助国家: 美国
• 起止时间: 1990-08-01 至 1993-07-31
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/3414560
• 关键词: biomarker; cats; chordate locomotion; cytochrome oxidase; gene expression; histochemistry /cytochemistry; immunocytochemistry; interneurons; limb movement; neural inhibition; neuroanatomy; neuronal transport; posture; protooncogene; spinal cord injury; spinal cord mapping; spinal cord surgery; spinal nerves; spinal reflex; spinal shock

The proposed research is concerned with mechanisms underlying the recovery of motor behavior after damage to spinal cord pathways in the adult cat. Quantitative kinematic analysis will be carried out to determine the rate and extent of recovery of locomotion and postural reflexes after damage to descending pathways or to dorsal root afferents. The first hypothesis is that the extent of recovery of motor behavior will be enhanced by reducing the initial degree of depression (spinal shock) that occurs after spinal transection. One side of the cord will be protected from spinal shock by making a chronic unilateral lesion prior to transection. Greater recovery on the side with prior hemisection than on the "acute" side (intra-animal comparison) would support the hypothesis. Greater recovery in this preparation than after transection alone (inter-animal comparison) would also provide support for the hypothesis. The second hypothesis concerns recovery of motor behavior after deafferentation. Preliminary results indicate that after unilateral hindlimb deafferentation, although overground and quadrupedal locomotion recover, bipedal locomotion does not recover. This failure is hypothesized to be due to descending inhibitory influences. Therefore, enhanced recovery of bipedal locomotion in the deafferented limb after subsequent destruction of descending pathways or pharmacological blockade of inhibitory systems would support the hypothesis. The third hypothesis concerns the relationship of metabolic activity in spinal neurons to recovery of motor behavior. Three activity-dependent markers will be examined quantitatively in the acute period and after recovery in the same preparations in which motor behavior is studied: 1) the transneuronal transport method of Jankowska in which WGA-HRP is transported retrogradely from motorneurons to interneurons; 2) cytochrome oxidase (CO) histochemistry; 3) induction of c-fos expression using c-fos protein immunoreactivity. An increase in metabolic activity or transport, or in the number of neurons exhibiting the markers in chronic preparations, compared to acute, would support the hypothesis that metabolic changes contribute to recovery. The fourth hypothesis is that different intraspinal pathways mediate recovery after different lesions. The localization of altered activity may be affected by the specific systems which mediate recovery. This hypothesis will be tested by mapping of WGA-HRP (transneuronal), CO, and c-fos in two different lesion models: hemisection and deafferentation, in which the recovered behavior and the pathways that mediate recovery are considerably different. Differential changes in localization of metabolic activity as a function of lesion type would support the hypothesis.

拟议的研究涉及恢复的机制 成年猫损伤脊髓途径后的运动行为。 定量运动学分析将进行确定速率 损害后的运动和姿势反射的恢复程度 下降的途径或背根部传入。第一个假设是 通过减少运动行为的恢复程度将增强 脊柱后发生的抑郁（脊柱冲击）的初始程度 横向。绳索的一侧将受到脊柱冲击的保护 在横断前进行慢性单侧病变。更大的恢复 在前面的侧面，而不是在“急性”侧（动物内部 比较）将支持该假设。在这方面有更大的恢复 制备比单独的横断后（动物间比较）将 还为假设提供支持。第二个假设问题 停用后运动行为的恢复。初步结果 表明单方面后肢脱落后，尽管 地上和四足运动恢复，双皮运动没有 恢复。假设这种故障是由于抑制作用而引起的 影响。因此，增强了双皮亚运动的恢复 随后破坏降落途径或 药理学阻断抑制系统将支持 假设。第三个假设涉及代谢的关系 脊柱神经元的活性对运动行为的恢复。三 活动依赖性标记将在急性中进行定量检查 在运动行为的相同准备工作中恢复的时期和恢复后 研究：1）Jankowska的跨神经元传输方法 WGA-HRP从运动神经元逆转到中间神经元； 2） 细胞色素氧化酶（CO）组织化学； 3）诱导C-FOS表达 使用C-FOS蛋白免疫反应性。代谢活动的增加或 运输，或在慢性中表现出标记的神经元数量 与急性相比，准备工作将支持以下假设 代谢变化有助于恢复。第四个假设是 不同的载体途径介导不同病变后的恢复。 改变活动的定位可能会受到特定的影响 介导恢复的系统。该假设将通过映射测试 在两个不同的病变模型中的WGA-HRP（跨神经元），CO和C-FOS： 恢复行为和恢复的行为和脱落 介导恢复的途径大不相同。微分 代谢活动的定位随病变类型的函数的变化 将支持假设。