A murine model of hypertonic saline as a treatment for acute spinal cord injury: effects on autonomic outcome Laboratory investigation


Howard B. Levene, Melanie B. Elliott, John P. Gaughan, Christopher M. Loftus, Ronald F. Tuma, and Jack I. Jallo


Spinal cord injury (SCI) continues to be a problem without a definitive cure. Research based on improved understanding of the immunological aspects of SCI has revealed targets for treating and ameliorating the extent of secondary injury. Hypertonic saline (HTS), a substance both easy to create and to transport, has been investigated as an immunologically active material that can be used in a clinically relevant interval after injury. In this pilot study, HTS was investigated in a murine model for its abilities to ameliorate secondary injury after a severe spinal cord contusion. Female C57Bl/6 mice with severe T8–10 contusion injuries were used as the model subjects. A group of 41 mice were studied in a blinded fashion. Mice received treatments with HTS (HTS, 7.5%) or normal saline solution (NSS, 0.9%) at 2 discreet time points (3 and 24 hours after injury.) A separate group of 9 untreated animals were also used as controls. Animals were assessed for autonomic outcome (bladder function). In a group of 33 mice, histological assessment (cellular infiltration) was also measured. Bladder function was found to be improved significantly in those treated with HTS compared with those who received NSS and also at later treatment times (24 hours) than at earlier treatment times (3 hours). Decreased cellular infiltration in each group correlated with bladder recovery. The increased effectiveness of later administration time of the more osmotically active and immunomodulatory substance (HTS) suggests that interaction with events occurring around 24 hours after injury is critical. These events may be related to the invasion of leukocytes peaking at 8–24 hours postinjury and/or the peak benefit time of subject rehydration.