Neural Debris Research Articles

FK506 rescues peripheral nerve allografts in acute rejection.

This study investigated the ability of the immunosuppressant FK506 to reverse nerve allograft rejection in progress. Eighty-four Buffalo rats received posterior tibial nerve grafts from either Lewis or Buffalo donor animals. Allografts were left untreated for either 7, 10, or 14 days before receiving daily subcutaneous FK506 injections (2 mg/kg). Time-matched control animals received either an isograft, an allograft with continuous FK506, or an allograft with no postoperative FK506 therapy. All animals underwent weekly evaluation of nerve function by walking track analysis. Experimental group animals were sacrificed either immediately prior to initiation of FK506 therapy (days 7, 10, or 14), after 2 weeks of immunosuppressive treatment, or 8 weeks postsurgery. Histomorphometric analysis, consisting of measurements of total number of nerve fibers, neural density, and percent of neural debris, demonstrated a statistically significant increase in regeneration in the isograft group relative to the untreated allograft group within 28 days of transplantation. Grafts harvested from animals receiving 2 weeks of FK506 after 7 or 10 days of rejection were histomorphometrically similar to time-matched isografts. By contrast, grafts from animals receiving 2 weeks of FK506 following 14 days without therapy resembled untreated allografts and demonstrated significant histomorphometric differences from isografts at the corresponding time point. Analysis of walking track data confirmed that relative to untreated allografts, functional recovery was hastened in animals receiving an isograft, or allograft treated with FK506. This study demonstrated that when started within 10 days of graft placement, FK506 could reverse nerve allograft rejection in rats evaluated following 2 weeks of treatment.

Immunolocalization of CD44 in the Dystrophic Rat Retina

The distribution of the cell surface adhesion/receptor molecule CD44 was studied in retinas of the Royal College of Surgeons (RCS) rat which exhibits an inherited retinal dystrophy. In this animal model, the retinal pigment epithelium fails to phagocytize shed photoreceptor outer segment material, a membranous debris layer accumulates in the subretinal space and the photoreceptor cells degenerate. Using immunoperoxidase and immunogold labeling, CD44 was localized to Müller cell apical microvilli in normal rat retinas, as noted in other species. For the RCS rat, immunoperoxidase labeling of 18 day and 1 month retinas showed the typical microvillar labeling pattern. At 2 months postnatal, following degeneration of most of the photoreceptors, a more condensed band of microvillar label was observed. At 3 months, when photoreceptor degeneration was virtually complete, only distinct regions of dense label remained between the neural retina and debris zone. Upon ultrastructural and immunogold analysis, these regions were found to contain closely packed Müller cell microvilli. At all ages studied, labeling for CD44 in the inner retina did not increase, as it does in other forms of retinal degeneration which lack a debris zone. However, by 3 months the debris zone was labeled for CD44 indicating that CD44 molecules remain on Müller cell microvilli and processes which have extended into and become part of the debris zone. This may be caused by an altered distribution of still undetermined ligands for CD44 which are present within the interphotoreceptor matrix of the RCS rat retina.

Wallerian degeneration of peripheral nerve. Age-dependent loss of nerve lipids.

The age-dependent loss of the major peripheral nerve lipids (cholesterol, phospholipid, and total galactolipid) was quantitated over a period of 9 weeks of Wallerian degeneration induced by surgical transection of rabbit sciatic nerves in animals of several ages. Proportionate losses of these lipids were determined by calculating the content of each lipid on a per nerve and on a per gram fresh weight basis remaining after a given period of Wallerian degeneration as a percent of original normal values at several time following surgery. The proportionate loss of each lipid from the distal stump was the most prompt and the most complete in nerves transected at 2 weeks of age, and the least in nerves transected at 20 weeks of age. The prompter clearance of these lipids from younger than older degenerating nerve gives convincing evidence that the suggestion from light-microscopic studies of faster clearance of neural debris in younger than in older animals is correct. A possible relationship between these biochemical findings and the phenomenon of greater functional recovery from peripheral nerve injury in younger than in older subjects is discussed.