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Prospective in vivo experimental animal model.To determine the effect of intra-arterial injection of the steroids commonly used for transforaminal epidurals on the central nervous system. And to determine if all of the steroids have the same effect.Transforaminal epidural steroid injection is commonly employed to treat radicular pain. This approach is associated with complications, including stroke and death. While the mechanism is unknown, the leading hypothesis is that intravascular injection of particulate steroids leads to microembolization.To characterize the nature of steroid induced injury, a rodent model was employed. The internal carotid artery was dissected and its branches ligated. The external carotid artery was ligated, mobilized, cannulated, and injectate administered. Five solutions were tested: Depo-Medrol (N = 11), Depo-Medrol carrier (N = 6), Solu-Medrol (N = 6), Decadron (N = 8), and normal saline (N = 7). Drugs, in volume of 50 μL, were injected into the ICA via the ECA cannula at 25 μL/min. The extent of central nervous system injury was evaluated by analysis of coronal sections of the brain.Cerebral hemorrhage occurred in test subjects with the following frequency: 8 of 11 in the Depo-Medrol group, 7 of 8 in the Solu-Medrol group, and 3 of 6 in the Depo-Medrol carrier group; no lesions were identified in the Decadron or saline groups (P < 0.01). Evan’s blue dye leakage was detected in the Depo-Medrol and Solu-Medrol groups, but not the Decadron or saline groups.This study presents the first in vivo evaluation of intra-arterial steroid injection. Data demonstrate Depo-Medrol, as well as its nonparticulate carrier, and Solu-Medrol can produce significant injury to the blood-brain barrier when injected intra-arterially. These results demonstrate that injury is produced not only by particulate obstruction of the cerebral microvasculature, but also by toxicity of the carrier or steroid (methylprednisolone).