Convective delivery of macromolecules into the naive and traumatized spinal cords of rats

Object. Many macromolecules have the potential to enhance recovery after in jury and other lesions of the spinal cord, but because of the limited penet ration of these compounds across the blood-spinal cord barrier, they cannot be used effectively. To determine if convective delivery could be used in a common animal model to investigate potential therapeutic macromolecules a nd to examine the effects of trauma on convective delivery in that model, t he authors examined the distribution of a macromolecule in naive and trauma tized rat spinal cords. Methods. Using convection, various infusion volumes ([Vi]; 1, 2, and 4 mu l ) of C-14-albumin were infused into the dorsal columns of 13 naive and five traumatized rat spinal cords. Volume of distribution (Vd), homogeneity, pe rcent age of recovery, and anatomical location were determined using quanti tative autoradiography, scintillation analysis, calculation of kurtosis (K) value, and histological analysis. In the nontraumatized group, Vd was line arly proportional (R-2 = 0.98) to Vi (Vd/Vi, 4.3 +/- 0.6; mean +/-. standar d deviation), with increases in Vd resulting from linear expansion (R-2 = 0 .94) primarily in the craniocaudal dimension. In the traumatized spinal cor ds, the Vd/Vi ratio (3.7 +/- 0.5) was smaller (p < 0.02) and distributions were less confined to the craniocaudal dimension, with significantly larger cross-sectional distributions in the region of injury (p < 0.02) compared to the noninjured spinal cords. Histological analysis revealed that after i nfusion into the dorsal columns, albumin distribution in naive cords was li mited to the dorsal white matter, but in the traumatized cords there was pe netration into the central gray matter. The distribution of the infusate wa s homogeneous in the nontraumatized (K = -1.1) and traumatized (K = -1.1) s pinal cords. Recovery of radioactivity was not significantly different (p > 0.05) between the nontraumatized (84.8 +/- 6.8%) and traumatized (79.7 +/- 12.1%) groups. Conclusions. Direct convective delivery of infusate can be used to distribu te macromolecules in a predictable, homogeneous manner over significant vol umes of naive and traumatized rat spinal cord. These characteristics make i t a valuable tool to investigate the therapeutic potential of various compo unds for the treatment of injury and spinal cord disease.