A re-assessment of the effects of treatment with an epidermal growth factor receptor (EGFR) inhibitor on recovery of bladder and locomotor function following thoracic spinal cord injury in rats

This study was undertaken as part of the NIH “Facilities of Research Excellence-Spinal Cord Injury” project to support independent replication of published studies. Here, we repeat an experiment in which rats that received an inhibitor of the epidermal growth factor receptor (EGFR) exhibited greater sparing/recovery of bladder and motor function and enhanced sparing at the lesion site after contusion injuries at the thoracic level. Young adult female Sprague-Dawley rats received moderate contusions with the NYU impactor (10 g from 12.5 mm, 2 mm rod diameter), and then were implanted with catheters attached to osmotic minipumps for intra-spinal delivery of either PD168393 dissolved in 5% DMSO and HBSS or vehicle alone. Motor function was assessed with the Basso, Beattie, and Bresnahan Locomotor Rating Scale (BBB) and with a grid walk task. Bladder function was assessed by measuring the amount of urine retained in the bladder. Tactile sensitivity was assessed using von Frey hairs and heat and cold sensitivity were assessed by testing hindlimb sensitivity to ethylchloride spray and a hotplate respectively. Rats that received PD168393 were more impaired on motor assessments and also showed greater bladder impairment (larger amounts of retained urine) than rats that received vehicle. These results thus fail to confirm previous studies reporting enhanced recovery following treatment with PD168393.

Research highlights► A previous report of a potential therapy for SCI is not confirmed. ► Treatment with an EGFR inhibitor can lead to larger lesions and greater impairment of function. ► There are major differences in the physicochemical properties of commercially available EGFR inhibitors.