RESUMO
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.
RESUMO
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.