Injury to the CNS leads to formation of scar tissue, which is important in sealing the lesion and inhibiting axon regeneration. The fibrotic scar that comprises a dense extracellular matrix is thought to originate from meningeal cells surrounding the CNS. However, using transgenic mice, we demonstrate that perivascular collagen1␣1 cells are the main source of the cellular composition of the fibrotic scar after contusive spinal cord injury in which the dura remains intact. Using genetic lineage tracing, light sheet fluorescent microscopy, and antigenic profiling, we identify collagen1␣1 cells as perivascular fibroblasts that are distinct from pericytes. Our results identify collagen1␣1 cells as a novel source of the fibrotic scar after spinal cord injury and shift the focus from the meninges to the vasculature during scar formation.

Sixty-two autogenous cephalic vein segments were grafted into the femoral arteries of 31 mongrel dogs, the left side receiving non-distended (control) grafts and the right side distended (experimental) grafts. Distending media were heparinized blood and saline. Veins were distended at 600 mm Hg for 2 minutes. Specimens were taken at intervals from 15 minutes to 3 months, and were studied by gross inspection, surface observations (light scanning stereoscope to X70 scanning electron microscope to X6,000) and routine histologic techniques (light microscope to X 1000). In general, grafting of veins in the arterial system was followed by progressive degenerative changes in all layers of the vein, including endothelial cell involution, desquamation and re-endothelialization. Often a variable degree of subendothelial fibrous and/or myoepithelial proliferation occurred which might compromise even a lumen lined by healthy endothelium. Distention caused these changes to occur earlier (2-4 weeks) and to be more pronounced. Distention with saline caused more damage to the endothelium than did distention with blood. We conclude that preimplant distention of vein grafts (to overcome spasm) should be employed sparingly, as it adversely affects the endothelial covering of the flow surface, accelerates the development of degenerative changes, and may predispose the graft to early thrombotic complications.

(ABSTRACT)Ten polymethylmethacrylate (PMMA) beads containing metronidazole (3 concentrations); gentamicin sulfate; or metronidazole and gentamicin sulfate were immersed in 5 ml of phosphate buffered saline in triplicate. Eluent was replaced at specified time intervals for 1 day (1, 3, 6, 12 and 24 hours), daily, or weekly for 21 days.Antibiotic concentrations were measured by High Performance Liquid Chromatography.Changes in antibiotic bioactivity attributable to polymerization or co-polymerization of the antibiotics with PMMA, ethylene oxide sterilization, and storage of antibioticimpregnated PMMA (AIPMMA) beads containing metronidazole were evaluated.Antibiotic elution patterns were similar for all groups. Day-1 elution for groups containing either metronidazole (3 concentrations) or gentamicin represented a mean 63% to 66% and 79% respectively of the 21-day total elution. Approximately 50% of the day-1 elution occurred during the first hour. The elution of metronidazole was dosedependent. There was no significant difference in the total amount of antibiotic eluted from groups that had the saline changed daily versus weekly. The elution of metronidazole (day 3-21) and gentamicin (all days) was significantly greater when metronidazole and gentamicin were combined (p<0.05). Polymerization of PMMA was delayed in groups containing metronidazole.Neither polymerization nor copolymerization of metronidazole and gentamicin with PMMA, gas-sterilization, or 2-month storage of beads containing metronidazole significantly affected antimicrobial bioactivity.Metronidazole elutes from PMMA. The frequency at which the saline was changed did not affect the rate of antibiotic elution.