大面积颅骨缺损对中枢神经系统影响的研究
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摘要
目的:建立中国实验小型猪单纯超大面积颅骨缺损动物模型,并使用此模型对颅骨缺损综合征发病机理及机制进行研究,并研究单纯大面积颅骨缺损会对中枢神经系统的中长期影响,指导临床治疗时机选择。
方法:采用北京农大培育的18月龄中国实验小型猪27头随机分为3个组,正常组3头,单纯颅骨缺损组12头和手术创伤对照组12头。对正常的中国实验小型猪的颅腔及脑的正常颅内压、脑含水量、脑脊液生化成份、脑电图和脑总灌注量进行测量,并对脑的顶叶(缺损区)和额叶(非缺损区)颅骨缺损综合征阳性症状的部分相关神经递质和脑受体分布密度的变化,进行了免疫组织化学染色观测。单纯颅骨缺损组12头实验动物,全麻下进行保留硬脑膜的全穹隆颅骨切除手术。按术后1月、3月、6月、12月对预定指标进行检测,并设立手术创伤对照。
结果:在中国实验小型猪身上,成功获得大面积颅骨缺损实验动物模型,动物模型的颅压下降数据改变符合既往临床病例数据趋势,缺损面积接近脑表面积一半≥40cm~2。发现大面积颅骨缺损不会造成长期的慢性脑水肿,不会造成长期的脑脊液生化成份的改变,大面积颅骨缺损会造成脑电异常,以及脑总灌注量在大面积缺损后的二次上升现象。发现单纯颅骨缺损所造成的颅腔生理改变会在长期造成缺损区及非缺损区的脑神经递质及受体发生变化,从而引起一系列相关症状,损害高峰出现在缺损出现6月左右。
结论:脑血流灌注和脑脊液循环的改变是最有可能造成颅骨缺损综合征众多症状的主要原因。大面积颅骨缺损应在缺损发生的6个月内行修复,以避免对中枢神经系统产生严重影响。
Objective
To explore a method of establishing a huge cranial defect animal model on mini pigs , the mechanisms of "Sinking Skin Flap Syndrome" and the effects of huge cranial defects on CNS.
Method
27 pigs more than 18 months old were randomized sent to 3 groups. Normal values of brain including ICP, ingredients of CSF, W/D ratio, EEG, total blood volume of inbrain were tested and recorded on group 1 within 3 normal pigs. The volume and distribution of GFAP, Serotomin, Serotonin receptor 1A, Glutamate ,Glutamate receptor 1 were stained and analyzed at gray matter of normal pig brain. 9 pigs in group 2 were operated to remove the full cranial bone. And they were tested as above at 1 month, 3 months, 6 months and 12 months post operation. 9 pigs in group 3 were taken as contrast team with the same strike of operation.
Result
The effects of post operation of the removal of full cranial bone were recorded. Some signs of SSFS were duplicated on this animal model. The regularity of ICP, ingredients of CSF, W/D ratio, EEG and total blood volume of inbrain were analyzed. Two climaxes of inbrain blood were found at post operation pigs. And the observed brain receptors and transmitters were found increased or decreased at different area.
Conclusion
The huge cranial defects would do harm to brain on mini pigs for a long duration. And CSF circulation changes and blood supply changes contribute a lot to the affections. All the changes happen at 6 months post operation mostly.
方法:采用北京农大培育的18月龄中国实验小型猪27头随机分为3个组,正常组3头,单纯颅骨缺损组12头和手术创伤对照组12头。对正常的中国实验小型猪的颅腔及脑的正常颅内压、脑含水量、脑脊液生化成份、脑电图和脑总灌注量进行测量,并对脑的顶叶(缺损区)和额叶(非缺损区)颅骨缺损综合征阳性症状的部分相关神经递质和脑受体分布密度的变化,进行了免疫组织化学染色观测。单纯颅骨缺损组12头实验动物,全麻下进行保留硬脑膜的全穹隆颅骨切除手术。按术后1月、3月、6月、12月对预定指标进行检测,并设立手术创伤对照。
结果:在中国实验小型猪身上,成功获得大面积颅骨缺损实验动物模型,动物模型的颅压下降数据改变符合既往临床病例数据趋势,缺损面积接近脑表面积一半≥40cm~2。发现大面积颅骨缺损不会造成长期的慢性脑水肿,不会造成长期的脑脊液生化成份的改变,大面积颅骨缺损会造成脑电异常,以及脑总灌注量在大面积缺损后的二次上升现象。发现单纯颅骨缺损所造成的颅腔生理改变会在长期造成缺损区及非缺损区的脑神经递质及受体发生变化,从而引起一系列相关症状,损害高峰出现在缺损出现6月左右。
结论:脑血流灌注和脑脊液循环的改变是最有可能造成颅骨缺损综合征众多症状的主要原因。大面积颅骨缺损应在缺损发生的6个月内行修复,以避免对中枢神经系统产生严重影响。
Objective
To explore a method of establishing a huge cranial defect animal model on mini pigs , the mechanisms of "Sinking Skin Flap Syndrome" and the effects of huge cranial defects on CNS.
Method
27 pigs more than 18 months old were randomized sent to 3 groups. Normal values of brain including ICP, ingredients of CSF, W/D ratio, EEG, total blood volume of inbrain were tested and recorded on group 1 within 3 normal pigs. The volume and distribution of GFAP, Serotomin, Serotonin receptor 1A, Glutamate ,Glutamate receptor 1 were stained and analyzed at gray matter of normal pig brain. 9 pigs in group 2 were operated to remove the full cranial bone. And they were tested as above at 1 month, 3 months, 6 months and 12 months post operation. 9 pigs in group 3 were taken as contrast team with the same strike of operation.
Result
The effects of post operation of the removal of full cranial bone were recorded. Some signs of SSFS were duplicated on this animal model. The regularity of ICP, ingredients of CSF, W/D ratio, EEG and total blood volume of inbrain were analyzed. Two climaxes of inbrain blood were found at post operation pigs. And the observed brain receptors and transmitters were found increased or decreased at different area.
Conclusion
The huge cranial defects would do harm to brain on mini pigs for a long duration. And CSF circulation changes and blood supply changes contribute a lot to the affections. All the changes happen at 6 months post operation mostly.
引文
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