End Organ Effects of High-Dose Human Equivalent Methylprednisolone in a Spinal Cord Injury Rat Model

Abstract

Interventional study. To analyze the histologic effects of high-dose human equivalent methylprednisolone on the pulmonary, cardiac, intestinal, renal, hepatic, and splenic tissues in a spinal cord injury rat model. There are numerous investigations of various medical interventions for the treatment of acute spinal cord trauma. Currently, the only generally accepted medical intervention in an acute spinal cord trauma is the intravenous administration of high doses of methylprednisolone. Although it has been nearly 2 decades since the first National Acute Spinal Cord Injury Study investigated the role high-dose steroids might play in the treatment of acute spinal cord trauma, controversy still exists regarding the efficacy of this treatment. To our knowledge, no study has examined the role of high-dose methylprednisolone in organ systems other than the spinal cord in an acute spinal cord injury model at the histologic level. This study attempts to characterize end organ histologic response to human dose equivalent (HDE) intravenous methylprednisolone administration in a rodent model of acute spinal cord injury. A total of 48 Sprague-Dawley rats were divided equally into control and experimental groups. Each group was subdivided into 6 sets of 4 animals each, according to intervals after injury. Groups 1-6 consisted of animals euthanized at 0, 4, 8, 16, 24, and 48 hours after spinal cord injury. Paraplegia after lower thoracic laminectomy was achieved using a standardized Allen weight drop technique. Within 1 hour of injury, experimental animals were treated with HDE methylprednisolone, infused for 23 hours continuously. Liver, kidney, lung, intestine, spleen, and heart were harvested at variable intervals after injury and prepared for histologic examination. These slides were analyzed with microscopic staining techniques and compared in a blinded manner by a qualified pathologist. Of all the end organs analyzed, the spleens were most affected. Lymphocytic depletion was seen in as little as 4 hours after methylprednisolone infusion and continued until 48 hours. Pulmonary tissues variably showed interstitial congestion and eosinophilic alveolar collections. Intestinal mucosal tissues showed edema and autolyzed mucosa from 16 hours onwards. Cardiac, kidney, and hepatic tissue did not differ significantly from controls. Histologically, HDE methylprednisolone caused significant splenic lymphocytic depletion changes in as little as 4 hours. This trend of end organ lymphocytopenia continued to progress until 48 hours. Pulmonary eosinophilic infiltrates were seen from 8 until 24 hours. Intestinal mucosal edema and necrosis were seen in samples at 16 hours throughout 48 hours. This study was designed to evaluate end organ changes seen in an animal model of an acute spinal cord injury treated with HDE methylprednisolone. Study animals were infused with HDE methylprednisolone given according to the National Acute Spinal Cord Injury Study II protocol. The kidney, lung, cardiac, intestinal, splenic, and hepatic tissues from the aforementioned animals were then sectioned and analyzed using histologic staining techniques by a qualified pathologist.