The Mechanisms Of Second Brain Injury And Cerebral Protection Of Basic Fibroblast Growth Factor After Diffuse Brain Injury In Rats

Objective To discuss the regularity and significance of histopathological change, water content, cortical apoptosis in brain tissues of rats following diffuse brain injuries. Methods To create Marmarou's diffuse brain injury model in rats. The cortical apoptosis were determined by Flow cytometry. Dry-wet method, histological techniques and electron microscope were used to determine water content in brain tissue and inflammatory reaction and ultrastructural blood capillary and neurons at different time phases. Results The cortical apoptosis rate and water content were upgraded after diffuse brain injury. The cortical apoptosis and water content increased at the 6h, peaked at the 72th h and the 24th h respectively, and then decreased. Traumatic groups contrast to sham-operated groups, the difference of interclass was statistical significance (P<0.05). Inflammatory reactions and ultra structures of blood capillary and neurons paralleled to the regularities of the cortical apoptosis and water content. Conclusions Ischemic and anoxemia were appeared and led to microcirculation disturbance after diffuse brain injuries. The structures of blood brain barrier were disorganized at last. The disorder of metabolic activity of neurocyte led to second brain injury. Brain edema influenced to the apoptosis and the expression tendency of them indicated the regularities of pathology in second brain injuries. Objective To investigate the different expression of intercellular adhesion molecule-1 after diffuse brain injury in rats and discuss its effect in second brain injury. Methods To create Marmarou's diffuse brain injury model in rats. Dry-wet method, Real-time quantitative PCR, immunohistochemistry, histological techniques and electron microscopic were used to determine water content of brain tissue, expression of ICAM-1 and its mRNA and neuronal damage at different time phases after diffuse brain injury in rats. Results Water content was upgraded after diffuse brain injury. Contrast to sham-operations group water content increased at the 6h (P<0.05), peaked the 24th h then decreased. Traumatic groups contrast to sham-operated groups, the difference of interclass was statistical significance (P<0.05). The expression of ICAM-1 started increase at the 6th h evidently (positive microvesseles count 4.8±0.8), peaked at the 72nd h (17.2±2.4) respectively (P<0.05). Its mRNA increased at the third h (ΔCt: 13.48±3.93) evidently, peaked at the 72nd h (20.59±0.97) and the level at 7d (15.60±0.01) were higher than sham-operated group (4.66±1.11) (P<0.01). Neurons were denaturalization, edema and necrosis diffusely, distinctly at the 72nd h under light microscopic and electron microscopic. Conclusions The expression of ICAM-1 was induced after diffuse brain injury in rats. This indicates that ICAM-1 is closely involved in patho-process of vascular brain edema and neuronal damage by interposing inflammatory reaction. Objective To observe effect of bFGF on expressions of intercellular adhesion molecule-1 after diffuse brain injury in rats and discuss its mechanism of cerebral protection. Methods To create traumatic and traumatic after pretreatment diffuse brain injury model by deforming Marmarou's diffuse brain injury model in rats. Dry-wet methods, Real-time quantitative PCR were used to determine water content of brain tissue, expression of ICAM-1mRNA in the two models. Results Contrast to traumatic groups, water content was similar and decreased at the same time in traumatic after pretreatment groups and the peak delayed to the 48th h. Water content had the statistical significance between the two groups(P<0.05) at the 6th h, the 12th h, the 24th h, the 48th h and the 72nd h respectively. The tendency in expressions of ICAM-1mRNA was similar in the two models in rats. The diversity of expressions of ICAM-lmRNA had the statistical significance at the 6th h (P<0.05), the 12th h(P<0.05), the 24th h(P<0.05), the 48th h(P<0.05), the 72nd h(P<0.001) and the day 7(P<0.001) respectively in the two traumatic brain injuries. Conclusions Expression of ICAM-lmRNA was been down-regulated by bFGF after diffuse brain injury. These indicated that the inhibitive effect of bFGF on expressions of ICAM-lmRNA would be one of mechanisms of bFGF cerebral protection. Objective To observe expressions of matrix metalloproteinase-9 mRNA and disscuss its effect in second brain injury. Methods To create Marmarou's diffuse brain injury model in rats. Dry-wet method, Real-time quantitative PCR, immunohistochemistry, histological techniques and electron microscopic were used to determine water content of brain tissue, expression of MMP-9 and its mRNA and microvessels and neuronal damage at different time phases after diffuse brain injury in rats. Results Water content was upgraded after diffuse brain injury. Contrast to sham-operations group water content increased at the 6h (P<0.05), peaked the 24th h then decreased. Expression of MMP-9 was mainly in neurons and endothelial cells and increased at 6th h, peaked at the 72nd h and decreased at the 7th day. Except the third hour and the 14th day group, positive cell counts had the statistical significance between the other groups (P<0.05). The expressions of MMP-9mRNA started increase at the first h, peaked at the 12th h respectively (P<0.01). Increased MMP-9mRNA levels persisted up to one week contrast to sham-operated groups. Ultra structures of blood capillaries and neurons were disorganized correspondingly. Conclusions The expressions of MMP-9mRNA were induced to increase after diffuse brain injury in rats. These finding suggested strongly that MMP-9 would involve in the cerebral edema of vascular origin and neuronal damage. To oppose to MMP-9 should be one of the target of clinical therapy. Objective To discuss the significance of expressions of tissue inhibitor of metalloproteinase-1mRNA and effect of bFGF on the expressions of MMP-9 and TIMP-1 after diffuse brain injury. Methods To create traumatic and traumatic after pretreatment diffuse brain injury model by deforming Marmarou's diffuse brain injury model in rats. Dry-wet methods, Real-time quantitative PCR were used to determine water content of brain tissue, expression of MMP-9mRNA and TIMP-1mRNA at different time phases. The cortical apoptosis were determined by Flow Cytometry. Results Contrast to traumatic groups, water content was similar and decreased at the same time in traumatic after pretreatment groups and the peak delayed to the 48th h. Water content had the statistical significance between the two groups(P<0.05) at the 6th h, the 12th h, the 24th h and the 72nd h respectively. Expressions of TIMP-1mRNA peaked at the 24th h and persist to the 7th day and increased one time contrast to sham-operated group. The diversity were the statistical significance (P<0.05) or highly significant (P<0.01) between the traumatic groups and traumatic after pretreatment groups except the 6th h groups. The diversity of MMP-9mRNA was the statistical significance at the 24th h and 72nd h between the two models. The cortical apoptosis increased, peaked at the 24th h then decreased. Conclusions The expressions of TIMP-1mRNA were induced to increase after diffuse brain injury in rats. TIMP-1 was involved in neuronal apoptosis independently. The imbalance between MMP-9 and TIMP-1 was involved in the cerebral edema of vascular origin and neuronal damage. The effect of bFGF on expressions of MMP-9mRNA and TIMP-1mRNA would be one of mechanisms of bFGF cerebral protection.