ABSTRACT
Objective Mild hypothermia (MHT) can effectively protect the brain in traumatic brain injury (TBI). This study was to investigate the effects of MHT on the calmodulin (CAM) expression and brain edema in the rat model of TBI. Methods Ninety adult SD rats were randomly divided into a sham operation, a normal temperature and an MHT group of equal number. Immediately after TBI, the rats of the MHT group maintained at a rectal temperature of (32 ± 0.5) °C for 6 hours. Modified neurological severity scores (mNSS) were obtained from 6 rats in each group at 1, 3, 5 and 7 days after modeling, and the rest of the animals subjected to brain MRI at 6, 12, 24 and 48 hours and then killed for determination of the CAM gene transcription and protein expression in the brain tissue by real-time PCR, immunohistochemistry and Western blot. Results The mNSSs were significantly higher in the MHT and normal temperature groups than in the sham operation control (P < 0.05) at all time points, neurological severity markedly decreased in the MHT group compared with the normal temperature group (P < 0.05). At 6, 12, 24 and 48 hours, the expression of CAM mRNA was remarkably down-regulated in the MHT group (1.83 ± 0.19, 1.72 ± 0.12, 1.59 ± 0.06 and 1.60 ± 0.07) in comparison with the normal temperature group (2.76 ± 0.25, 2.49 ± 0.18, 2.04 ± 0.14 and 1.65 ± 0.09) (P < 0.05), even lower in the MHT than in the normal temperature group (P < 0.05), but higher in both of the two groups than in the sham operation group (P < 0.05). At 6, 12, 24 and 48 hours, the volume of brain edema was significantly reduced in the MHT group ([32.14 ± 4.52], [36.52 ± 4.10], [42.10 ± 4.38] and [46.25 ± 5.02] mm3) as compared with the normal temperature group ([48.56 ± 5.35], [53.13 ± 6.31], [59.23 ± 6.82] and [62.35 ± 7.25] mm3) (P < 0.05). Conclusion Mild hypothermia can improve the neurological function and reduce the CAM expression and brain edema in the brain tissue of rats with traumatic brain injury, which may be related to the neuroprotective effect of mild hypothermia.
ABSTRACT
Objective Few studies are reported on the protective effect of valproic acid (VPA) against traumatic brain injury (TBI) by down-regulating the protein expressions of matrix metalloproteinase-9 (MMP-9) and aquaporin-4 (AQP-4) in the brain tissue. This study aimed to investigate the neuroprotective effects of different doses of VPA against TBI in experimental rats. Methods We randomly divided 100 adult male rats into five groups of equal number, sham operation, TBI model, and low- (30 mg), medium- (150 mg) and high-dose (300 mg) VPA treatment. At 1, 3, 7 and 14 days after modeling by controlled cortex impact, we obtained the modified Neurological Severity Scores (mNSS), measured the VPA concentration in the venous blood, and then killed the rats and harvested the brain tissue for determination of the water content using the dry-wet method and the expressions of MMP-9 and AQP-4 by Western blot and immunohistochemistry. Results At 1, 3, 7 and 14 days after modeling, the mNSSs in the high-dose VPA group were 4.6 ± 1.3, 3.8 ± 1.3, 3.0 ± 0.7 and 1.8 ± 0.8, respectively, significantly lower than 8.4 ± 0.9, 7.0 ± 0.7, 5.8 ± 1.0 and 4.5 ± 1.3 in the TBI group (P < 0.05), decreasing in a time-dependent manner, with statistically significant difference between any two dose groups (P < 0.05). At 1, 3 and 7 days, the water contents in the brain tissue were (76.2 ± 0.7)%, (76.9 ± 1.7)% and (73.9 ± 1.3)% in the high-dose VPA group, significantly lower than (79.6 ± 0.8)%, (82.6 ± 0.8)% and (78.6 ± 0.7)% in the TBI group (P < 0.05), also decreasing in a time-dependent manner, with statistically significant difference between any two dose groups (P < 0.05). At 1 and 3 days, the expressions of MMP-9 and AQP-4 in the brain tissue were markedly down-regulated in the VPA groups in a dose-dependent manner as compared with those in the TBI group (P < 0.05), with statistically significant difference between any two dose groups (P < 0.05), and meanwhile immunohistochemistry showed large numbers of cells with positive expressions of MMP-9 and AQP-4, which were reduced with the increased dose of VPA. Conclusion VPA has a neuroprotective effect against TBI in rats by inhibiting the expressions of MMP-9 and AQP-4 proteins in the brain tissue and alleviating brain edema. Within the range of the doses studied, higher-dose VPA produces a better effect.
ABSTRACT
Objective The expressions of inflammatory factors and brain edema after traumatic brain injury (TBI) are the main factors for deterioration of the condition.TBI after drunkenness is even more difficult to be managed than simple TBI.This study was to discuss the effects of drunkenness on the inflammatory factors TNF-o and IL-6 and the aquaporin-4 (AQP-4) protein in rats after TBI.Methods Forty-eight male adult SD rats were randomly divided into a TBI and an ethanol (ETH) pretreatment group.TBI was induced using the Feeney's method after intraperitoneal injection of 3％ chloral hydrate at 30 mg/kg (the TBI group) or following gavage of ETH (the ETH group).At 1,3 and 5 days after modeling,modified neurological function scores (mNSS) were obtained,the expressions of TNF-α,IL-6 and AQP-4 protein determined by Western blot,and the levels of TNF-α.IL-6 and AOP-4 mRNA measured by RT-PCR at 6,24 and 72 hours.Results Compared with the TBI group,the ETH group showed significantly decreased mNSS at 1 day (9.00±0.63 vs 7.17±1.72,P＜0.05),3 days (7.00±1.10 vs 4.83±1.47,P＜0.05) and 5 days after modeling (5.50±1.05 vs 3.83± 0.75,P＜ 0.05),but remarkably up-regulated expressions of TNF-α (0.068± 0.008 vs 0.257 ± 0.008,P＜ 0.01),IL-6 (0.102 ±0.013 vs 0.320±0.016,P＜0.01) and APQ4 (0.054±0.007 vs 0.212±0.015,P＜0.01) at 6 hours,as well as at 24 and 72 hours (P＜0.01).Conclusion Drunkenness may increase the expressions of inflammatory factors and brain edema after traumatic brain injury and consequently aggravate secondary brain injury.
ABSTRACT
Objective To study the clinical and imaging features of patients with bone metastases from breast cancer and identify the factors related to the incidence of bone metastases. Methods Three hundred and thirty-four patients with breast cancer were recruited into this study. Whole-body 99Tcm-methylene disphosphonate (MDP) bone scan, clinical staging, pathological, immunohistochemical and serological test results were analyzed retrospectively. χ2 test was used for statistical analysis. Results The incidence rate of bone metastases for patients with and without lymph node metastases was 71% (152/214) and 22. 5% (27/120), respectively (χ2 =72.80, P =0.000). The incidence rate of bone metastases from infiltrated non-specified and specified breast cancer was 69% (203/294) and 41.7% (5/12), respectively (χ2 =3. 97, P=0.046). Alkaline phosphatase (ALP) was elevated in 28.5% (51/179) and 14.9%(11/74) of patients with and without bone metastases, respectively (χ2 = 5. 25, P = 0.022 ). Carcinoembryonic antigen (CEA), carbohydrate antigen (CA) 15-3, CA125, CA19-9 increased in 68.7% ( 123/179) and 27.0% (20/74) of patients with and without bone metastases, respectively (χ2 = 37. 03, P =0. 000). Conclusions The incidence of bone metastases from breast cancer is correlated to pathological types of primary tumor and lymph node metastases. Bone metastases occurs more frequently in patients with infiltrated, non-specified, primary cancer and with lymph node metastases. Serum ALP, CEA, CA15-3,CA125, CA19-9 might be the tumor makers for early diagnosis of bone metastases from breast cancer.