Correlation Of The Expression Of Vascular Regeneration Adjustment Factor And Microvascular Dynamic Changes In Traumatic Brain Edema

Objective:We produce the rat model of traumatic brain injury by the improved Feeney’s freefall combating method in this study. Detecting the expression levels of ES, VEGF and FLK-1in rats after traumatic brain injury, we explore the relationship among the dynamic changes of microvascular surface density, moisture content of brain tissue and them.Not only to help to elucidate the pathophysiological mechanisms of traumatic brain edema, but it also can provide new ideas and methods for inducing angiogenesis in ischemic area effectively, improving supply of local blood and promoting remodeling and functional repair of neurovascular structures.Methods:Part1:60Wistar rats were randomly divided into a control group and trauma group.According to the processing time after traumatic brain edema each group was further divided into six subgroups(N=5).The rats were respectively killed at6h,12h,1d,3d,7d and14d different time points. We produce animal models of traumatic brain injury reference to the improved Feeney’s freefall combating method. Based on the balancing, emancipating, head branching, walking, escaping and the reaction of limbs of the rat after injury, we make neurological score of their behavior by the Modified neurological severity score system.Using wet and dry weighing method, we detect changes of moisture content of brain tissue timely to monitor the process of the development of cerebral edema.Part2:On the basis of experiment Part1, we use immunohistochemistry to assay the expression of ES, VEGF and FLK-1in the brain tissue of injury peri cortex and hippocampus of rats. We mark injury peri vascular endothelial cells with the CD34to count MVD, calculate microvascular surface density using the Media Cyberretics Image ProPlus6.0image analysis system and explore the relationship of the expression of ES, VEGF, FLK-land CD34in traumatic brain injury through the results processed statistically.Result:1. Successfully producing animal model of traumatic brain injuryThe behavior of animal models of traumatic brain injury by the improved Feeney’s freefall combating method change, just as deep breathing, movement disorder of contralateral limb in brain trauma, reducing of proprioceptive and reflective ability, decreasing of balance significantly. The animals in group6h can not stay on the beam stably, at least one claw falling off. Neither they can walk straight or the escaping and reaction of limbs to pain significantly slow. Comparing with the corresponding subgroup of the control group, overall score increased statistically significant (P<0.01) using the modified neurological severity score system.The neurological deficit of animals in group12h continues to grow, so the overall score was higher compared to group6h in a statistically significant differ ence.The overall of group1d rates peak. The animals of this group try to balance in balance beam test and drop in the20-40s. The pain reaction of animals in group3-7d improve gradually over the previous, but there are still motor dysfunction. Every indicator of group14d returned to normal, but the difference of the overall ratings is still statistically significant compared with the control group(P<0.01).Moisture content of traumatic brain tissue begin to rise statistically significant after injury6h (P<0.05) compared with the control group. The edema gets peak in1-3d, begins to decline continued3d, decrease back to normal in7d. The difference was not significant in14d compared with the control igroup statistically(P>0.05).2. The relationship between the neurological severity score of rats and the changes of microvascularAccording to the mNSS scoring system, the neurological severity score after traumatic brain injury in rats is higher than in the control group and got top in3d. The microvascular surface density of trauma group immediately and statistically significant decreased after injury compared with the control group(P＜0.01) and the differences gradually reduce later. The MVD of trauma group growth quickly in1d. There is no significant differences compared with the control group to14d.The neurological severity score and MVD in damaged brain tissue of rats in trauma group was positively correlated by statistical analysis, so the regeneration and reconstruction of the micro vascular of damaged brain tissue can improve the blood supply of the ischemic area, restore the function of damaged neurons and control the damage of traumatic brain injury on central neurons fundamentally.3. The discipline of the expression of angiogenesis regulatory factors after traumatic brain injuryVascular is jointly regenerated by endogenous vascular regeneration regulatory factor-vascular regeneration factor and vascular regeneration inhibitor which involved in the regulation. The expression changes of ES in the brain tissue surrounding damage foci cortex and hippocampus of rat can not be detected obviously6-12h after traumatic brain injury. The content of ES increased rapidly after injury Id and reached its peak in3d. The expression levels of ES gradually decline in7-14d, but it is still higher than normal (P＜0.01).The number of VEGF-positive cells after injury are more than the control group in each period. The positive expression of VEGF is the strongest in Id and continued to3d. It goes down in14d but still be higher than that in the control group (P＜0.05).FLK-1that VEGF receptor showed no significant change6-12h after traumatic brain injury. The expression of FLK-1significantly increases after injury, reaches a peak in3d, rapidly declines in7d. It was higher than normal levels in14d, but there is no significant differences compared to the normal group(P>0.05).4. The relationship of the expression of ES, VEGFand FLK-1and the dynamic changes of microvascularIn the early period of traumatic brain injury, FLK-1has not expressed accompanied by the increasing expression of VEGF resulting in the interruption of VEGF signaling pathway, the drastically reduction of MVD and the significant increasing of moisture content of brain tissue. This state don not improved until the expression of FLK-1increase after trauma Id. After this period, the leading role of the dynamic equilibrium state of VEGF and ES controls the change of the MVD. ES’s crest slightly lags the Flk-1’s.Conclusion:1. The animal models of traumatic brain injury produced by the improved Feeney’s freefall combating method can be successfully simulate the pathological process of clinical traumatic brain edema caused by accelerate violence.2. The dynamic changes of microvascular caused by multiple factors after traumatic brain injury affect neurological status directly.3. The changes of expression of the Multiple vascular regeneration regulatory factors after traumatic brain injury regulating the changes of the microcirculation together and affecting the development of secondary brain injury are important part of the traumatic brain injury.