Cloutier Frank, Kalincik Tomas, Lauschke Jenny, Tuxworth Gervase, Cavanagh Brenton, Meedeniya Adrian, Mackay-Sim Alan, Carrive Pascal, Waite Phil
School of Medical Sciences, University of New South Wales, Sydney, NSW, Australia.
Department of Medicine, University of Melbourne, Melbourne, VIC, Australia; Department of Neurology, Royal Melbourne Hospital, Melbourne, VIC, Australia.
Auton Neurosci. 2016 Dec;201:17-23. doi: 10.1016/j.autneu.2016.08.015. Epub 2016 Aug 24.
Autonomic dysreflexia is a common complication after high level spinal cord injury and can be life-threatening. We have previously shown that the acute transplantation of olfactory ensheathing cells into the lesion site of rats transected at the fourth thoracic spinal cord level reduced autonomic dysreflexia up to 8weeks after spinal cord injury. This beneficial effect was correlated with changes in the morphology of sympathetic preganglionic neurons despite the olfactory cells surviving no longer than 3weeks. Thus the transitory presence of olfactory ensheathing cells at the injury site initiated long-term functional as well as morphological changes in the sympathetic preganglionic neurons. The primary aim of the present study was to evaluate whether olfactory ensheathing cells survive after transplantation within the parenchyma close to sympathetic preganglionic neurons and whether, in this position, they still reduce the duration of autonomic dysreflexia and modulate sympathetic preganglionic neuron morphology. The second aim was to quantify the density of synapses on the somata of sympathetic preganglionic neurons with the hypothesis that the reduction of autonomic dysreflexia requires synaptic changes. As a third aim, we evaluated the cell type-specificity of olfactory ensheathing cells by comparing their effects with a control group transplanted with fibroblasts. Animals transplanted with OECs had a faster recovery from hypertension induced by colorectal distension at 6 and 7weeks but not at 8weeks after T4 spinal cord transection. Olfactory ensheathing cells survived for at least 8weeks and were observed adjacent to sympathetic preganglionic neurons whose overall number of primary dendrites was reduced and the synaptic density on the somata increased, both caudal to the lesion site. Our results showed a long term cell type-specific effects of olfactory ensheathing cells on sympathetic preganglionic neurons morphology and on the synaptic density on their somata, and a transient cell type-specific reduction of autonomic dysreflexia.
自主神经反射异常是高位脊髓损伤后常见的并发症,且可能危及生命。我们之前已经表明,将嗅鞘细胞急性移植到第四胸髓水平横断的大鼠损伤部位,可在脊髓损伤后长达8周减轻自主神经反射异常。尽管嗅鞘细胞存活不超过3周,但这种有益作用与交感神经节前神经元形态的改变相关。因此,损伤部位嗅鞘细胞的短暂存在引发了交感神经节前神经元的长期功能以及形态变化。本研究的主要目的是评估嗅鞘细胞移植到靠近交感神经节前神经元的实质内后是否存活,以及在这个位置它们是否仍然能缩短自主神经反射异常的持续时间并调节交感神经节前神经元形态。第二个目的是量化交感神经节前神经元胞体上突触的密度,假设自主神经反射异常的减轻需要突触改变。作为第三个目的,我们通过将嗅鞘细胞的作用与移植成纤维细胞的对照组进行比较,评估嗅鞘细胞的细胞类型特异性。在T4脊髓横断后6周和7周,但不是8周时,移植嗅鞘细胞的动物从结肠扩张诱导的高血压中恢复得更快。嗅鞘细胞存活至少8周,并在交感神经节前神经元附近被观察到,这些神经元的初级树突总数减少,损伤部位尾侧的胞体上突触密度增加。我们的结果显示,嗅鞘细胞对交感神经节前神经元形态及其胞体上的突触密度具有长期的细胞类型特异性作用,以及对自主神经反射异常有短暂的细胞类型特异性减轻作用。