The effect of hypothermia on the expression of TIMP-3 after traumatic brain injury in rats.

Abstract

To investigate the effect of hypothermia on the expression of apoptosis-regulating protein TIMP-3 after fluid percussion traumatic brain injury (TBI) in rats. 210 adult male Sprague Dawley rats were randomly assigned to the groups of TBI with hypothermia treatment (32 degrees C), TBI with normothermia (37 degrees C), and sham injured control. TBI model was induced by 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 4 hours. All the rats were killed at 4, 6, 12, 24, 48, 72h and 1w after TBI. The mRNA and protein level of TIMP-3 in both injured and uninjured hemispheres of each group were measured using RT-PCR and western blot techniques. In the normothermic group, TIMP-3 levels in both 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 such an increase. According to the RT-PCR and western blot analysis, 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 of the corresponding values in the normothermic group in injured and uninjured hemispheres (cortex and hippocampus) by hypothermia treatment, respectively (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%+/-2.50and 54.76%+/-1.40 (p < 0.01). Our data suggests that moderate F-P brain injury would significantly upregulate TIMP-3 expression, while such an increase could be efficiently suppressed by hypothermia treatment.