SPINAL CORD TRANSECTION: A QUANTITATIVE ANALYSIS OF ELEMENTS OF THE CONNECTIVE TISSUE MATRIX FORMED WITHIN THE SITE OF LESION FOLLOWING ADMINISTRATION OF PIROMEN, CYTOXAN OR TRYPSIN

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Abstract
Long-Evans hooded rats were cordotomized at the T[thoracic]-5 level and given either cyclophosphamide (cytoxan), an immunosuppressive, piromen, a bacterial polysaccharide-nucleic acid complex, topical and systemic trypsin or no further specific treatment. Because of past and present controversy surrounding the proposed ability of these agents to promote spinal cord regeneration, a systematic study, employing light [microscopy] and EM, and quantitative methods in a single animal model, was done to re-evaluate the effects of each treatment on the connective tissue matrix which forms in the defect left by transection. After an initial inflammatory reaction during the 1st wk after surgery, the lesion zone is characterized either by areas of dense collagenous connective tissue with occasional fibroblasts and macrophages, or a loose areolar tissue with numerous sheets and cords of mesodermal cellular elements but minimal collagen. By 45 days postoperatively (dpo), axons supported by Schwann cells invade and become entangled in the loose connective tissue matrix. With longer postoperative survival, cysts appear cranial and caudad to the lesion and erode much of the scar together with viable neural tissue. Giving cytoxan or piromen did not result in any qualitative alteration of the scar matrix as evidenced by EM. Quantitative analysis revealed a slight reduction in the fibrous connective tissue component of the scar at 45-90 dpo, but this was transient when longer postoperative periods were studied. Trypsin caused a significant reduction in the amount of fibrous connective tissue with a concomitant increase in loose connective tissue and the appearance of a few distinctive, compact bundles of unmyelinated axons lacking Schwann cells.