title: 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 (32°C), TBI with normothermia (37°C), and sham-injured controls. TBI was induced by a fluid percussion TBI device. Mild hypothermia (32°C) was achieved by partial immersion in a water bath (0°C) 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 ± 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.
authors.affiliation: 1 Department of Neurosurgery, Shanghai Renji Hospital, Shanghai JiaoTong University , School of Medicine, Shanghai, China .
authors.forename: Feng
authors.initials: F
authors.lastname: Jia
authors.forename: Qing
authors.initials: Q
authors.lastname: Mao
authors.forename: Yu-Min
authors.initials: YM
authors.lastname: Liang
authors.forename: Ji-Yao
authors.initials: JY
authors.lastname: Jiang
mesh_terms: D000818:Animals; D015153:Blotting, Western; D001831:Body Temperature / Q000502:physiology; D001930:Brain Injuries / Q000378:metabolism* / Q000473:pathology; D002540:Cerebral Cortex / Q000378:metabolism / Q000473:pathology; D007839:Functional Laterality / Q000502:physiology; D006624:Hippocampus / Q000378:metabolism / Q000473:pathology; D007036:Hypothermia, Induced; D008297:Male; D012333:RNA, Messenger / Q000096:biosynthesis / Q000235:genetics; D051381:Rats; D017207:Rats, Sprague-Dawley; D060888:Real-Time Polymerase Chain Reaction; D019717:Tissue Inhibitor of Metalloproteinase-3 / Q000096:biosynthesis* / Q000235:genetics
chemical_list: D012333:RNA, Messenger; D019717:Tissue Inhibitor of Metalloproteinase-3