Weaver Lynne C, Marsh Daniel R, Gris Denis, Brown Arthur, Dekaban Gregory A
Spinal Cord Injury Team, BioTherapeutics Research Group, Robarts Research Institute, 100 Perth Drive, P.O. Box 5015, London, ON N6A 5K8, Canada.
Prog Brain Res. 2006;152:245-63. doi: 10.1016/S0079-6123(05)52016-8.
Spinal reflexes dominate cardiovascular control after spinal cord injury (SCI). These reflexes are no longer restrained by descending control and they can be impacted by degenerative and plastic changes within the injured cord. Autonomic dysreflexia is a condition of episodic hypertension that stems from spinal reflexes initiated by sensory input entering the spinal cord caudal to the site of injury. This hypertension greatly detracts from the quality of life for people with cord injury and can be life-threatening. Changes in the spinal cord contribute substantially to the development of this condition. Rodent models are ideal for investigating these changes. Within the spinal cord, injury-induced plasticity leads to nerve growth factor (NGF)-dependent enlargement of the central arbor of a sub-population of sensory neurons. This enlarged arbor can provide increased afferent input to the spinal reflex, intensifying autonomic dysreflexia. Treatments such as antibodies against NGF can limit this afferent sprouting, and diminish the magnitude of dysreflexia. To assess treatments, a compression model of SCI that leads to progressive secondary damage, and also to some white matter sparing, is very useful. The types of spinal reflexes that likely mediate autonomic dysreflexia are highly susceptible to inhibitory influences of bulbospinal pathways traversing the white matter. Compression models of cord injury reveal that treatments that spare white matter axons also markedly reduce autonomic dysreflexia. One such treatment is an antibody to the integrin CD11d expressed by inflammatory leukocytes that enter the cord acutely after injury and cause significant secondary damage. This antibody blocks integrin-mediated leukocyte entry, resulting in greatly reduced white-matter damage and decreased autonomic dysreflexia after cord injury. Understanding the mechanisms for autonomic dysreflexia will provide us with strategies for treatments that, if given early after cord injury, can prevent this serious disorder from developing.
脊髓损伤（SCI）后，脊髓反射在心血管控制中起主导作用。这些反射不再受下行控制的约束，并且会受到受损脊髓内退行性和可塑性变化的影响。自主神经反射异常是一种发作性高血压病症，源于损伤部位尾侧的脊髓传入感觉输入引发的脊髓反射。这种高血压严重影响脊髓损伤患者的生活质量，甚至可能危及生命。脊髓的变化在很大程度上促成了这种病症的发展。啮齿动物模型是研究这些变化的理想选择。在脊髓内，损伤诱导的可塑性导致感觉神经元亚群的中枢树突在神经生长因子（NGF）的作用下增大。这种增大的树突可增加对脊髓反射的传入输入，加剧自主神经反射异常。诸如抗NGF抗体之类的治疗方法可限制这种传入性芽生，并减轻反射异常的程度。为了评估治疗效果，一种导致进行性继发性损伤且能保留部分白质的脊髓损伤压迫模型非常有用。可能介导自主神经反射异常的脊髓反射类型极易受到穿过白质的延髓脊髓通路的抑制性影响。脊髓损伤压迫模型表明，保留白质轴突的治疗方法也能显著减轻自主神经反射异常。其中一种治疗方法是针对炎症白细胞表达的整合素CD11d的抗体，这些白细胞在损伤后急性进入脊髓并造成严重的继发性损伤。这种抗体可阻断整合素介导的白细胞进入，从而大大减少脊髓损伤后的白质损伤并减轻自主神经反射异常。了解自主神经反射异常的机制将为我们提供治疗策略，如果在脊髓损伤后早期给予这些治疗，可预防这种严重病症的发生。
