The Effect of Hypothermia on the Expression of TIMP-3 after Traumatic Brain Injury in Rats

Here we investigate the effect of hypothermia on the expression of apoptosis-regulating protein TIMP-3 after fluid percussion traumatic brain injury (TBI) in rats. We began with 210 adult male Sprague-Dawley rats and randomly assigned them to three groups: TBI with hypothermia treatment (32 degrees C), TBI with normothermia (37 degrees C), and sham-injured controls. TBI was induced by a fluid percussion TBI device. Mild hypothermia (32 degrees C) was achieved by partial immersion in a water bath (0 degrees C) under general anesthesia for 4h. The rats were killed at 4, 6, 12, 24, 48, and 72h and 1 week after TBI. The mRNA and protein level of TIMP-3 in both the injured and uninjured hemispheres of the brains from each group were measured using RT-PCR and Western blotting. In the normothermic group, TIMP-3 levels in both the injured and uninjured hemispheres were significantly increased after TBI compared with those of sham-injured animals (p<0.01). In contrast, post-traumatic hypothermia significantly attenuated this increase. According to the RT-PCR and Western blot analyses, the maximum mRNA levels of TIMP-3 were reduced to 60.60 +/- 2.30%, 55.83 +/- 1.80%, 66.03 +/- 2.10%, and 64.51 +/- 1.50%, respectively, of the corresponding values in the normothermic group in the injured and uninjured hemispheres (cortex and hippocampus) of the hypothermia group (p<0.01), while the respective maximum protein levels of TIMP-3 were reduced to 57.50 +/- 1.50, 52.67 +/- 2.20, 60.31 +/- 2.50 and 54.76 +/- 1.40 (p<0.01). Our data suggest that moderate fluid percussion brain injury significantly upregulates TIMP-3 expression, and that this increase may be suppressed by hypothermia treatment.