Goldsmith H S, de la Torre J C
Boston University School of Medicine, Department of Surgery, MA 02118.
Brain Res. 1992 Sep 4;589(2):217-24. doi: 10.1016/0006-8993(92)91280-r.
Following complete transection of the spinal cord, cats were separated into 2 groups to undergo: (i) surgical reconstruction of the disconnected cord using a neuroactive agent mixed into a collagen matrix bridge and omental transposition and (ii) cord transection-only. After 90 days, animals were killed and the brain and spinal cord were removed for immunohistochemistry. Two weeks prior to sacrifice, spinal cord blood flows were measured and the retrograde axonal tracer Fluoro-Gold was injected below the transection site. Gross inspection of the spinal cords at autopsy showed excellent integration and continuity of the collagen matrix bridge with the proximal-distal stumps in the surgical reconstruction group. In the transection-only group, the proximal-distal stumps were connected by a fibrotic, often tapered in the middle, tissue bridge. Results show that omental transposition in the surgical reconstruction group increased spinal cord blood flow by 58% when compared to transection-only animals. Fluoro-Gold was found in mesencephalic and brainstem catecholaminergic and cholinergic neurons known to send axons to the spinal cord. Immunohistochemical staining with antibodies against catecholamine synthesizing enzymes tyrosine hydroxylase (TH) and dopamine-beta-hydroxylase (DBH) showed that surgical reconstruction treated cat cords but not transection-only, developed dense bundles of dopaminergic and noradrenergic fibers which were present in the collagen matrix bridge and in the distal spinal cord. Extension of these catecholaminergic fibers in surgical reconstruction treated cats showed maximal outgrowth of 90 mm below the transection site when the neuroactive agent 4-aminopyridine was mixed into the collagen matrix. In addition, the synaptogenic marker synaptophysin (SYN) was observed on preganglionic sympathetic neurons in association with dopaminergic- and noradrenergic-containing varicosities distal to the collagen matrix bridge, an indication that neo-synaptic contacts may have been made on these previously denervated neurons. No TH, DBH or SYN was observed below the transection site in transection-only cats. These findings indicate that surgical reconstruction treated cords can develop dense supraspinal fiber outgrowth across a treated collagen matrix bridge fed by an omental blood supply and that these fibers may have made neo-synaptic contacts with appropriate distal spinal cord target tissue.
在脊髓完全横断后，将猫分为两组进行如下处理：(i) 使用混入神经活性剂的胶原基质桥和网膜移位术对离断的脊髓进行手术重建；(ii) 仅进行脊髓横断。90天后，处死动物并取出脑和脊髓进行免疫组织化学分析。在处死前两周，测量脊髓血流并在横断部位下方注射逆行轴突示踪剂荧光金。尸检时对脊髓的大体检查显示，手术重建组中胶原基质桥与近端 - 远端残端的整合和连续性良好。在仅横断组中，近端 - 远端残端由一个纤维化的、通常在中间变细的组织桥连接。结果显示，与仅横断的动物相比，手术重建组中的网膜移位使脊髓血流增加了58%。在已知向脊髓发送轴突的中脑和脑干儿茶酚胺能及胆碱能神经元中发现了荧光金。用针对儿茶酚胺合成酶酪氨酸羟化酶 (TH) 和多巴胺 - β - 羟化酶 (DBH) 的抗体进行免疫组织化学染色显示，手术重建处理的猫脊髓而非仅横断的脊髓，形成了密集的多巴胺能和去甲肾上腺素能纤维束，这些纤维束存在于胶原基质桥和远端脊髓中。当将神经活性剂4 - 氨基吡啶混入胶原基质时，手术重建处理的猫中这些儿茶酚胺能纤维在横断部位下方的最大生长长度为90毫米。此外，在胶原基质桥远端含有多巴胺能和去甲肾上腺素能的曲张体的节前交感神经元上观察到了突触形成标记物突触素 (SYN)，这表明在这些先前失神经支配的神经元上可能已经形成了新的突触联系。在仅横断的猫的横断部位下方未观察到TH、DBH或SYN。这些发现表明，手术重建处理的脊髓可以在由网膜血液供应的处理过的胶原基质桥上形成密集的脊髓上纤维生长，并且这些纤维可能已经与适当的远端脊髓靶组织形成了新的突触联系。
