Nanobubble technology to treat spinal cord ischemic injury

Background: Spinal cord ischemic injury is a severe complication of aortic surgery. We hypothesized that cerebrospinal fluid (CSF) oxygenation with nanobubbles after reperfusion could ameliorate spinal cord ischemic injury. Methods: Twenty white Japanese rabbits were categorized into 4 groups of 5 rabbits each: sham group, with balloon catheter insertion into the aorta; ischemia group, with spinal cord ischemic injury by abdominal aortic occlusion; nonoxygenated group, with nonoxygenated artificial CSF irrigation after spinal cord ischemic injury; and oxygenated group, with oxygenated artificial CSF irrigation after spinal cord ischemic injury. At 48 hours after spinal cord ischemic injury, the modified Tarlov score to reflect hind limb movement was evaluated. The spinal cord was histopathologically examined by counting anterior horn cells, and microarray and quantitative reverse-transcription polymerase chain reaction (qRT-PCR) analyses were performed. Results: The oxygenated group showed improved neurologic function compared with the ischemia and nonoxygenated groups (P < .01 and P = .019, respectively). Anterior horn neuron prevention in the sham, nonoxygenated, and oxygenated groups was confirmed (mean modified Tarlov score: sham, 9.2 ± 1.9; nonoxygenated, 10.2 ± 2.2; oxygenated, 10.4 ± 2.2; ischemia, 2.7 ± 2.7). Microarray analysis identified 644 genes with twofold or greater increased signals between the ischemia and sham groups. Thirty-three genes related to inflammatory response were enriched among genes differentially expressed between the oxygenated and ischemia groups. Interleukin (IL)-6 and tumor necrosis factor (TNF) expression levels were significantly lower in the oxygenated group compared with the ischemia group, while qRT-PCR showed lower IL-6 and TNF expression levels in the oxygenated group compared with the ischemia group (P < .05). Conclusions: CSF oxygenation with nanobubbles after reperfusion can ameliorate spinal cord ischemic injury and suppress inflammatory responses in the spinal cord.