Early functional outcomes and histological analysis after spinal cord compression injury in rats

Abstract

Object: Neuroprotective and repair strategies in spinal cord injuries (SCIs) have been so far largely unsuccessful. One of the prerequisites is the use of appropriate preclinical models to decipher pathophysiological mechanisms; another is the identification of optimal time windows for therapeutic interventions. The authors undertook this study to characterize early motor, sensory, autonomic, and histological outcomes after balloon compression of the spinal cord at the T8-9 level in adult rats.

Methods: A total of 91 rats were used in this study. Spinal cord balloon compression was performed at T8-9 in adult rats by inflation of a 2 Fr Fogarty catheter into the epidural space. The authors first characterized early motor, sensory, and autonomic outcomes of 2 volumes of compression (10 and 15 microl) using behavioral tests and then examined histological outcomes in the spinal cord using Luxol fast blue staining. To further substantiate the characterization of the epidural balloon-compression model, they used a noncompetitive N-methyl-D-aspartate antagonist, GK11, and demonstrated the involvement of excitotoxicity in this model.

Results: Proportional and reproducible functional impairment resulted from compression caused by balloon inflation with either 10 or 15 microl of water and corresponded to the extent of the lesion. Indeed, during the early phase following SCI (1 week postinjury), recovery of locomotor function and bladder control correlated with the volume of inflation, whereas outcomes with respect to sensory function and reflexes were independent of compression severity. Treatment with GK11 significantly improved motor function in all groups of rats 1 week after injury and bladder voiding in the 10-microl injured rats compared to the 15-microl injured rats.

Conclusions: The results of this study demonstrate that spinal balloon-compression injury in the rat is a well-characterized, reproducible, and predictable model to analyze early events following SCI.