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

Laboratory investigation

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Object

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.

Methods

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.

Results

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.

Conclusions

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.

Abbreviations used in this paper: BBB = Basso-Beattie-Bresnahan; HTS = hypertonic saline; NSS = normal saline solution; SCI = spinal cord injury.

Article Information

Address correspondence to: Jack I. Jallo, M.D., Ph.D., 3401 North Broad Street, Suite C540, Philadelphia, Pennsylvania 19140. email: jack.jallo@temple.edu.

Current affiliation for Dr. Jallo: Department of Neurosurgery, Thomas Jefferson University, Philadelphia, Pennsylvania.

Current affiliation for Dr. Levene: Department of Neurological Surgery, University of Miami, Miller School of Medicine, Miami, Florida.

Please include this information when citing this paper: published online December 3, 2010; DOI: 10.3171/2010.9.SPINE08314.

© AANS, except where prohibited by US copyright law.

Headings

Figures

  • View in gallery

    Photomicrographs of spinal cord sections stained with H & E showing leukocyte infiltration (small, darker stained cells) and green outlined region of interest. There is less infiltration for the HTS group (upper) compared with NSS at 3 hours (lower). Black arrows indicate the region most proximal to the lesion.

  • View in gallery

    Upper: Bladder functional recovery. The percentage of mice recovering bladder function improved with increased tonicity of treatment fluid (HTS vs NSS) as well as in increased time interval to treat (24 vs 3 hours). The mice treated at 24 hours with HTS reached statistical significance compared those receiving no treatment (no tx) (*p < 0.05). Lower: Average day of bladder recovery. Mice that recovered function tended to recover by about the same day regardless of the tonicity of treatment. Note that untreated mice recovered at a later time on average.

  • View in gallery

    Percentage of cellular infiltration as a function of time. Note that all groups treated with HTS have decreased cellularity from 14 to 28 days. The group with the highest cellularity received treatment at 3 hours with NSS. Statistical significance: *p < 0.05 compared with 3-hour NSS and 24-hour HTS. **p < 0.001 compared with 3-hr NSS. ***p < 0.01 compared with 3-hour NSS.

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