Abstract

OBJECTIVE: This laboratory has demonstrated that lipid-coated microbubbles (LCM) effectively aggregate and deliver chemotherapeutic drugs into rat brain tumor cells, and antigliosis agents into maturing rat brain injury sites. In this study, we report the affinity of tail-vein-injected LCM to the injured rat spinal cord by a compressive lesion to the upper thoracic region.
METHODS: The accumulation of LCM into the injured spinal cord was analyzed by labeling it with a lipid-soluble fluorescent dye, diO. Indices of glial fibrillary acidic protein (GFAP) were measured concomitantly with diO-labeled LCM using confocal microscopy.
RESULTS: There was no aggregation of LCM at 1 and 6 hours post-injury; however, by 2, 4, and 7 days post-injury, there was a clear affinity of LCM for the injured region. LCM aggregation shifted from the central necrotic area of the injury on post-injury day (PID) 2 and 4, to the peripheral white matter among GFAP-positive astrocytes by PID 7.
CONCLUSION: LCM's affinity for spinal cord injury sites may be mediated in the early stages by proliferating macrophages in the necrotic center, then in later stages by GFAP-positive astrocytes in the peripheral white matter. These findings suggest a potential for using LCM as a delivery vehicle to concentrate lipid-soluble antigliosis agents, steroids, or NMDA antagonists into spinal cord injury sites.