Neuroprotective effect of preoperatively induced mild hypothermia as determined by biomarkers and histopathological estimation in a rat subdural hematoma decompression model.
Neuroprotective effect of preoperatively induced mild hypothermia as determined by biomarkers and histopathological estimation in a rat subdural hematoma decompression model.
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DOI：
10.3171/2012.10.jns12725
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发表时间：
2013-02
影响因子：
4.1
通讯作者：
Bullock MR
中科院分区：
文献类型：
--
作者：
Yokobori S;Gajavelli S;Mondello S;Mo-Seaney J;Bramlett HM;Dietrich WD;Bullock MR
In traumatic brain injury (TBI) patients, hypothermia therapy has not shown efficacy in multicenter clinical trials. With the post-hoc data from the latest clinical trial (NABIS:H II), we hypothesized that hypothermia may be beneficial in the rat acute subdural hematoma (ASDH) model by blunting the effects of ischemic/ reperfusional (I/R) injury. The major aim of our study was to test the efficacy of temperature management in reducing brain damage after ASDH. Rats were induced with ASDH and placed into (1) Normothermia group (37°C) (2) Early hypothermia group; head and body temperature reduced to 33°C at 30 minutes prior to craniotomy (3) Late hypothermia group; temperature was lowered to 33°C at 30 minutes after decompression (4) Sham group; no ASDH and underwent only craniotomy with normothermia. To assess of neuronal and glial cell damage, we analyzed microdialysate (MD ; using 100kD probe) concentrations of: glial fibrillary acidic protein (GFAP) and ubiquitin carboxyl-terminal hydrolase-L1 (UCH-L1). Fluoro-Jade B (FJB) positive neurons and injury volume with 2,3,5-triphenyltetrazolium chloride (TTC) staining were also measured. In the early phase of reperfusion (30min- 2.5 hrs after decompression), extracellular UCH-L1 in the early hypothermia group was significantly lower than in the normothermia. (Early; 4.9±1.0 ng/dl, Late; 35.2±12.1 ng/dl, Normo; 50.20± 28.3 ng/dl, Sham; 3.1±1.3 ng/dl, Early vs Normo; p < 0.01, Sham vs Normo; p < 0.01, analyzed with ANOVA followed by a post-hoc Bonferroni’s test ). In the late phase of reperfusion (> 2.5hrs after decompression), extracellular GFAP in the early hypothermia group was also lower than in the normothermia and late hypothermia groups (Early; 5.5±2.9 ng/dl, Late; 7.4±3.4 ng/dl, Normo; 15.3±8.4 ng/dl, Sham; 3.3±1.0 ng/dl, Normo vs Sham; p < 0.01). The number of FJB positive cells in early hypothermia group was significantly smaller than in normothermia group (Normo vs Early: 774,588 ± 162,173 vs 180,903 ± 42,212, p<0.05). Also, the injury area and volume were smaller in the early hypothermia group in which hypothermia was induced before craniotomy and cerebral reperfusion (115.2±15.4 mm3 in early hypothermia group, 344.7±29.1 mm3 in late hypothermia group, 311.2±79.2 mm3 in Normothermia group p<0.05). In conclusion, the data suggests early, preoperatively induced hypothermia could mediate the reduction of neuronal and glial damage in reperfusional phase of ischemic/reperfusional brain injury.
