Effect of postinjury intravenous or intrathecal methylprednisolone on spinal cord excitatory amino-acid release, nitric oxide generation, PGE2 synthesis, and myeloperoxidase content in a pig model of acute spinal cord injury

Abstract

Objectives: To determine whether postinjury methylprednisolone could reduce the generation of known mediators of secondary neurological injury. Methods: Intrathecal microdialysis probes were used to sample cerebrospinal fluid (CSF) for measurement of PGE 2 , glutamate, and citrulline (a byproduct of nitric oxide generation), before and after spinal cord injury in anesthetized pigs. The spinal cord was removed at the end of the study for measurement of myeloperoxidase and methylprednisolone concentrations. Animals were randomly allocated to receive intravenous methylprednisolone (30 mg/kg bolus then 3.4 mg/kg/h), intrathecal methylprednisolone (5 mg bolus then 5 mg/h), or saline, beginning 30 min after the spinal cord was injured by using a modification of the Allen weight drop technique. Results: Spinal cord injury significantly increased the amount of glutamate, PGE 2 , myeloperoxidase, and citrulline, recovered from the CSF dialysates. However, neither intravenous nor intrathecal methylprednisolone administered after injury had any effect on the magnitude of the increase in any of the measured biochemicals. Intrathecal methylprednisolone administration produced a spinal cord methylprednisolone concentration that was eight times greater, and a plasma concentration that was 32 times less, than that achieved with intravenous administration. Conclusions: Contrary to earlier animal studies in which methylprednisolone was administered either before or immediately after spinal cord injury, we found no effect of intravenous or intrathecal methylprednisolone on any of the parameters measured when administered 30 min postinjury.

Neuroprotective Effects of Direct Intrathecal Administration of Granulocyte Colony‐Stimulating Factor in Rats with Spinal Cord Injury

“…Compared to systemic administration, i.t. MP administration resulted in a 30‐fold increase in MP concentration in the spinal cord and a greater than 300‐fold increase in the therapeutic index of MP . The present results clearly indicate that central administration of MP and G‐CSF improved the SCI‐induced neurological dysfunctions in rats.…”

Development of a large-animal model to measure dynamic cerebrospinal fluid pressure during spinal cord injury

“…Pigs are well established as pediatric and adult models of traumatic brain injury, 28 chronic spinal cord pathology, 12,21,78 and ischemic SCI. 66 Traumatic SCI pig models have used weightdrop, 9 pneumatic impactor, 52 and clip compression 79,92 techniques. In our opinion, pigs are a suitable SCI model because their CNS is similar to that of humans in several respects, including blood supply and flow characteristics, 30,80 white and gray matter distribution, brain and spinal cord growth and development, 22 and spinal skeletal similarities.…”

Bioavailability Effect of Methylprednisolone by Polymeric Micelles

“…In addition, recent reports have indicated that Pglycoprotein (MDR1)-mediated exclusion of MP from the spinal cord (14,15) and that MDR1 is capable of interfering with the absorption of MP in the rat small intestine (16). Poor response to the MP therapy was therefore, proposed to be possibly due to incomplete absorption of the MP by overexpression of MDR1 in the GI tract.…”