Trehalose protects against spinal cord ischemia in rabbits

ObjectiveThis study tested to see if trehalose, a cytoprotective disaccharide, protects against spinal cord ischemia in a rabbit model.MethodsThe infrarenal aorta was mobilized in four groups of 10 rabbits. In groups I, II, and III, it was clamped proximally and distally for 20 minutes. In group I, the clamped aorta was infused at 2.5 L/min for 2 hours with lactated Ringer's (LR) solution. In group II, the clamped aorta was infused with 5% trehalose in LR. LR was administered intravenously (2.0 mL/min) in groups I and II starting 30 minutes before clamping. In group III, 5% trehalose in LR was infused intravenously only. Group IV was a sham-operated control group without aortic clamping. At 8, 24, and 48 hours after reperfusion, hind limb function was scored using the Tarlov score (paralysis = 0, perceptible joint movement = 1, good joint movement but unable to stand = 2, able to walk = 3, normal = 4). Histologic analysis and electron microscopy were performed on anterior horn cells.ResultsThe Tarlov scores in groups I, II, and III were, respectively, 1.1 ± 1.4, 3.5 ± 0.5, and 2.9 ± 0.9 at 8 hours; 0.8 ± 1.2, 3.9 ± 0.3, and 2.9 ± 0.9 at 24 hours; and 0.6 ± 0.7, 3.9 ± 0.3, and 2.7 ± 0.9 at 48 hours after reperfusion. Group IV scores were normal (4 ± 0) at all assessments. These scores were higher in groups II and III than in group I (P < .01) at all assessments. Scores at 24 and 48 hours were higher in group II than in group III (P < .05). In group III, delayed paraparesis developed in one rabbit at 24 hours and in two more at 48 hours. Histopathologic analysis showed the number of normal neurons was higher in groups II (P < .0001), III (P = .006), and IV (P < .0001) vs group I. Electron microscopy confirmed preserved neuronal cell ultrastructure in rabbits with normal limb function.ConclusionsTransaortic trehalose infusion was protective against paraplegia, whereas intravenous trehalose reduced spinal cord ischemia. This study was preliminary and further studies are needed.

Clinical RelevanceSpinal cord injury after surgical repair of the thoracic or thoracoabdominal aorta is a disastrous complication. Recently, many kinds of adjunctive therapy have been reported to be successful, including our previous reports of cold saline and free-radical scavengers in a rabbit model of spinal cord ischemia; however, some rabbits still became paraplegic. The total prevention of paraplegia due to spinal cord ischemia may require the development of a more effective adjunct. Trehalose, a unique nonreducing disaccharide, stabilizes cell membranes under various stressful conditions such as heat, freezing, osmotic shock, and dehydration. Trehalose has been used clinically as a solution for lung preservation in transplantation. This study demonstrated the protective effect of a trehalose infusion into the clamped segment of the aorta or transvenously to prevent spinal cord damage after spinal cord ischemia in an animal model. Further research is needed, but the results of this study may be applicable not only to open surgery but also to thoracoabdominal endovascular repair.