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

Abstract

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 (328C), TBI with normothermia (378C), and sham-injured controls. TBI was induced by a fluid percussion TBI device. Mild hypothermia (328C) was achieved by partial immersion in a water bath (08C) under general anesthesia for 4 h. The rats were killed at 4, 6, 12, 24, 48, and 72 h 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 AE 2.30%, 55.83 AE 1.80%, 66.03 AE 2.10%, and 64.51 AE 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 AE 1.50, 52.67 AE 2.20, 60.31 AE 2.50 and 54.76 AE 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.

Therapeutic Hypothermia as a Neuroprotective Strategy in Neonatal Hypoxic-Ischemic Brain Injury and Traumatic Brain Injury

“…Induction of hypothermia at 32 +/− 0.5°C regulates the calpain changes and provides protection against TBI as shown in in vitro cultured rat neurons [65]. Further, 32°C hypothermia decrease the levels of caspase-3 mRNA and immunoreactivity and attenuated the activation of TIMP-3 after fluid percussion injury in Sprague-Dawley rats [66]. Hypothermia at 30°C attenuates calpain-mediated degradation of microtublule-associated protein 2, thus reducing cytoskeletal damage in the hippocampus following TBI [67].…”