title: Extensive scarring induced by chronic intrathecal tubing augmented cord tissue damage and worsened functional recovery after rat spinal cord injury.
abstract: Intrathecal infusion has been widely used to directly deliver drugs or neurotrophins to a lesion site following spinal cord injury. Evidence shows that intrathecal infusion is efficient for 7 days but is markedly reduced after 14 days, due to time dependent occlusion. In addition, extensive fibrotic scarring is commonly observed with intrathecal infusion. These anomalies need to be clearly elucidated in histology. In the present study, all adult Long-Evans rats received a 25 mm contusion injury on spinal cord T10 produced using the NYU impactor device. Immediately after injury, catheter tubing with an outer diameter of 0.38 mm was inserted through a small dural opening at L3 into the subdural space with the tubing tip positioned near the injury site. The tubing was connected to an Alzet mini pump, which was filled with saline solution and was placed subcutaneously. Injured rats without tubing served as control. Rats were behaviorally tested for 6 weeks using the BBB locomotor rating scale and histologically assessed for tissue scarring. Six weeks later, we found that the intrathecal tubing caused extensive scarring and inflammation, related to neutrophils, macrophages and plasma cells. The tubing's tip was occluded by scar tissue and inflammatory cells. The scar tissue surrounding the tubing consists of 20-70 layers of fibroblasts and densely compacted collagen fibers, seriously compressing and damaging the cord tissue. BBB scores of rats with intrathecal tubing were significantly lower than control rats (p<0.01) from 2 weeks after injury, implying serious impairment of functional recovery caused by the scarring.
authors.affiliation: Spinal Cord Society Research Center, Fort Collins, CO 80526, USA. szhang@qwestoffice.net
authors.forename: Shu-xin
authors.initials: SX
authors.lastname: Zhang
authors.forename: Fengfa
authors.initials: F
authors.lastname: Huang
authors.forename: Mary
authors.initials: M
authors.lastname: Gates
authors.forename: Jason
authors.initials: J
authors.lastname: White
authors.forename: Eric G
authors.initials: EG
authors.lastname: Holmberg
mesh_terms: D000818:Animals; D002408:Catheters, Indwelling / Q000009:adverse effects; D002921:Cicatrix / Q000209:etiology* / Q000473:pathology* / Q000503:physiopathology; D000075202:Contraindications; D004185:Disability Evaluation; D004195:Disease Models, Animal; D015918:Infusion Pumps, Implantable / Q000009:adverse effects*; D007278:Injections, Spinal / Q000009:adverse effects / Q000295:instrumentation; D009043:Motor Activity / Q000502:physiology; D051381:Rats; D020318:Rats, Long-Evans; D020127:Recovery of Function / Q000502:physiology; D013117:Spinal Cord Compression / Q000209:etiology* / Q000473:pathology* / Q000503:physiopathology