Greater clinical understanding of the pivotal role of apoptosis in
spinal cord injury (SCI) has led to new and innovative apoptosis-based
therapies for patients with an SCI.
Tauroursodeoxycholic acid (
TUDCA) is a biliary
acid with antiapoptotic properties. To our knowledge, this is the first study in the English language to evaluate the therapeutic efficacy of
TUDCA in an experimental model of SCI. Thirty rats were randomized into three groups (
sham-operated,
trauma only, and
trauma plus
TUDCA treatment) of 10 each. In groups 2 and 3,
spinal cord trauma was produced at the T8-T10 level via the Allen weight drop technique. Rats in group 3 were treated with
TUDCA (200 mg/kg intraperitoneal) 1 min after
trauma. The rats were killed either 24 h or 5 days after injury. The
neuroprotective effect of
TUDCA on injured spinal cord tissue and the effects of that agent on the recovery of hind-limb function were assessed. The efficacy of treatment was evaluated with histopathologic examination and
terminal deoxynucleotidyl transferase-mediated dUTP-
biotin nick-end labeling (TUNEL) analysis. Histopathologic characteristics were analyzed by comparison of
hematoxylin-and-
eosin stained specimens. Neurologic evaluations were performed 24 h, 3 days, and 5 days after
trauma. Hind-limb function was assessed with the inclined plane technique of Rivlin and Tator and the modified version of Tarlov's grading scale. Twenty-four hours after injury, there was a significantly higher number of apoptotic cells in the lesioned spinal cord group than in the
sham-operated control group. Treatment of the rats with
TUDCA significantly reduced the number of apoptotic cells (4.52+/-0.30 vs. 2.31+/-0.24 in group 2) and the degree of tissue injury. Histopathologic examination showed that group 3 rats had better spinal cord architecture compared with group 2 rats. Five days after injury, the mean inclined plane angles in groups 1, 2, and 3 were 65.50 degrees +/- 2.09, 42.00 degrees +/- 2.74, and 53.50 degrees +/- 1.36. Motor grading of the rats revealed a similar trend. These differences were statistically significant (p<0.05). The mechanism of neuroprotection in the treated rats, although not yet elucidated, may be related to the marked antiapoptotic properties of
TUDCA. A therapeutic strategy using
TUDCA may eventually lead to effective treatment of SCI without toxic effects in humans.