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

Introduction: There are numerous investigations into 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 two decades since the first NASCIS investigated the role high dose steroids might play in the treatment of acute spinal cord trauma, controversy still exists with regards to 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. This study attempts to characterize end organ histologic response to human dose equivalent (HDE) intravenous methyprednisolone (MP) administration in a rodent model of acute spinal cord injury.

Materials and Methods: Forty-eight Sprague-Dawley rats were divided equally into control and experimental groups. Each group was subdivided into eight sets of three animals each, according to post-injury intervals. Groups 1-8 consisted of animals sacrificed at T= 0,4,8,12,16,24,48 and 72 hours after spinal cord injury. Paraplegia after lower thoracic laminectomy was achieved using a standardized Allen weight drop technique.

Within one hour of injury, experimental animals were treated with HDE MP, infused for 23 hours continuously. Liver, kidney and spleen were harvested at variable intervals postinjury and prepared for histologic examination.

Edema, hemorrhagic necrosis, lymphocytosis/lymphopenia (for spleen sections) and fatty degeneration (for liver sections) in specimens from treated and control groups were graded by microscopic staining techniques and compared in a blinded manner by a qualified pathologist.

Results: Minimal differences were observed between control and treated groups at zero and twenty four hours. At twenty-four hours there was a noted increase in cellular necrosis in all specimens treated with HDE MP, this continued for both 48 and 72 hours. The liver specimens showed marked fatty degenerative changes in 24 hours and this progressed in both 48 and 72 hour specimens. The spleen specimens showed a marked lymphocytopenia at twenty four hours and this progressed in both 48 and 72 hour specimens.

Conclusions: Histologically MDE MP caused significant end organ degenerative changes in as little as twenty four hours. This trend of end organ degenerative change continued to progress for 48 and 72 hours.