大剂量激素治疗创伤性脑水肿的动物实验研究

本文报道了大剂量激素治疗创伤性脑水肿的动物实验结果。SD 雄性大鼠52只,随机分为4组,按自由落体法致大鼠脑挫裂伤后,分别一次静脉注射甲基强的松龙30mg/kg,地塞米松5mg/kg,地塞米松0.5mg/kg 和等量生理盐水。6小时后取脑测定脑肿胀、创伤侧伊文氏蓝增量和伊文氏蓝表面蓝染直径,脑水肿标本送光镜和电镜检查。结果显示创伤早期应用大剂量激素可减轻脑水肿,减少蛋白渗出,为临床应用提供参考价值。     

创伤性脑水肿研究进展

创伤性脑水肿是重型颅脑创伤后最重要的继发性病理生理反应，其病理改变特点是过多的水分积聚在脑细胞内外间隙，脑体积增大，导致和加重颅内压增高，甚至引起脑移位和脑疝，是致死和致残的主要原因。创伤性脑水肿的发生机制十分复杂，其基础和临床救治的研究一直是神经外科研究最为关注的领域。近年来，对脑水肿发生机制的研究有了更深入的认识，并提出了一些防治脑水肿的新观点和新方法，提高了颅脑创伤的救治水平。     

颅脑创伤后伤侧受损皮层rCBF的变化与脑水肿关系的实验研究

目的 研究家兔颅脑创伤后伤例受损皮层局部脑血流量(rCBF)的变化与脑水肿变化的关系。方法 利用BIM—Ⅱ型生物撞击机造成家兔重型颅脑损伤，测量其伤侧受损皮层不同时相的rCBF和脑组织含水量。结果 颅脑创伤后受损皮层rCBF显降低，脑组织含水量显升高，在各时相点与对照组有非常显差异(P＜0．01)，且二成负相相关系(P＜0．01)。结论 颅脑创伤引起了rCBF和脑组织含水量变化，受损皮层rCBF减少可能是脑水肿形成的重要影响因素。     

大鼠流体冲击致脑损伤后海马循环的变化

目的 :探讨大鼠闭合性脑损伤后 ,脑循环功能的改变规律。方法 :应用流体冲击致大鼠脑损伤模型 ,采用氢清除法和二胺基联苯胺染色及图像分析 ,观察大鼠海马血流量及海马血管密度的变化。结果 :大鼠脑损伤后 1h海马血流量开始下降 ,4h达最低 ,8h后逐渐恢复 ;与此同时海马血管密度在伤后 4h升高达峰值 ,8h后渐下降至伤前水平。结论 :大鼠流体冲击致脑损伤后 ,海马血流量的降低与血管密度破坏性的增加表明脑循环明显受损     

大鼠液压脑损伤后皮层微血管改变与脑水肿的关系

目的探讨大鼠液压脑损伤后皮层微血管损伤情况及其与伤后脑水肿的关系。方法成年SD大鼠30只,随机分为正常组（n=6）、假手术组（n：6）、损伤组（n=18）,其中损伤组分为伤后6h、24h、72h三亚组,每亚组6只。利用液压冲击法建立大鼠颅脑损伤模型,显微镜下观察直接损伤侧和非直接损伤侧皮层微血管损伤隋况,CD34标记血管内皮细胞评价血管密度改变,干湿重法检测脑组织含水量的变化。结果大鼠皮层微血管损伤后6h可见血管支行迂曲、扩张、充血,伤后24h可见少量血栓形成,损伤后72h可见有较多血栓形成。损伤组CD34阳性细胞数明显低于假手术组和对照组（P〈0．05）,而脑组织含水量明显高于假手术组和对照组（P〈0．05）,而后两组无统计学差异（P〉O．05）。损伤组直接损伤侧皮层微血管损伤较非直接损伤组严重,而且伤后24h较伤后6、72h严重。结论颅脑损伤后脑微血管损伤为全脑性血管损伤,这可能是伤后脑水肿形成的机制之一。     

低温治疗大鼠创伤性脑损伤对脑水肿及IL-1β的影响

目的研究低温治疗大鼠创伤性脑损伤后对脑水含量、Na^＋含量及白细胞介素-1β（IL-1β）的影响，以探讨低温的治疗作用及可能机制。方法采用Feeney打击模型，分别进行全身低温、全脑低温或局灶低温治疗，治疗结束后检测伤灶脑组织含水量、Na^＋含量、IL-1β含量、IL-1β蛋白表达及IL-1βmRNA表达。结果局灶低温组及全身低温组在脑水含量、Na^＋含量、IL-1β含量、IL-1β蛋白表达、IL-1βmRNA表达方面低于脑外伤模型组（P〈0．05），且局灶低温组低于全身低温组（P〈0．05）；而全脑低温组在上述方面高于脑外伤模型组（P〈0．05）。结论局灶低温及全身低温治疗能明显减轻脑水肿，且局灶低温效果更佳；全脑低温治疗加重脑水肿；其机制之一可能是通过抑制或促进炎性因子IL-1β表达而起作用。     

冷冻致兔脑水肿模型的建立与改进

目的:建立和改进一种冷冻诱导的兔局限性脑水肿模型。方法:采用液氮冷冻探头单点置于兔一侧大脑半球硬膜外,时间为60s,制作成局灶性脑冷冻伤后脑水肿模型。6h后断头取脑,计算脑含水量和脑组织伊文氏蓝含量,观察伊文氏蓝染色范围及其病理改变。结果:实验组冷冻侧脑含水量比对侧及对照组左、右半球明显增加(P<0.001)。伊文氏蓝含量(mg/g干脑重)也较对侧及对照组左半球和右半球显著增多(P<0.001)。冷冻灶周围有明显的蓝染带,局部脑组织稍膨隆。光镜检查见细胞肿胀明显,透亮度增加,部分细胞空泡样变性,血管周围间隙显著增宽,并可见灶性出血,部分区域液化。电镜检查见部分神经细胞内细胞器(线粒体、内质网)肿胀或消失。部分核碎裂或溶解,血管基底膜肿胀或断裂等表现。对照组无类似改变。结论:本实验模型重复性较强,稳定可靠,条件较易控制。冷冻伤脑水肿是一种典型的血管源性脑水肿,与创伤性脑水肿有极其相似之处,可广泛应用于创伤性脑水肿的各种实验研究。     

依达拉奉预处理对大鼠脑损伤后细胞毒性脑水肿的影响

目的探讨依达拉奉预处理对大鼠创伤性脑损伤的治疗作用及其机制。方法 SD大鼠38只,随机分为生理盐水对照组(Control组)和依达拉奉预处理组(EV组)。采用测干、湿重法检测不同剂量EV预处理对大鼠脑组织含水量的影响和Western-blot检测脑组织中水通道蛋白4(AQP4)及钠-钾-氯共转运体1(NKCC1)等蛋白表达情况。结果与生理盐水对照组比较,EV能明显减轻神经功能障碍,干、湿重法检测结果显示,EV明显减轻大鼠脑组织含水量,Western-blot结果提示EV下调AQP4、NKCC1蛋白的表达,组间差异有统计学意义(P<0.05)。结论 EV预处理能减轻创伤性脑水肿,具有显著的神经保护作用,可能是通过调控AQP4和NKCC1而减轻脑组织水肿。     

白蛋白减轻大鼠液压颅脑损伤伤后脑水肿和神经功能障碍的剂量效应

目的 探讨白蛋白在治疗大鼠液压颅脑损伤后神经功能恢复和脑组织含水量的剂量效应。方法 将96只SD大鼠随机分为4组,液压打击致伤。伤后30min经尾静脉注射2g/kg(n=24,Ⅰ组)、1.2g/kg(n=24,Ⅱ组)、0.8g/kg(n=24,Ⅲ组)、0.4g/kg(n=24,Ⅳ组)20％人血白蛋白。每组取12只伤前、伤后当日、伤后连续7d进行行走、平衡和记忆实验,记录神经功能恢复情况。另每组12只伤后48h取双侧大脑半球测湿重、干重,计算脑组织含水量。结果 实验Ⅰ组动物的行走实验、平衡实验、记忆均优于其他组(P<0.01)。实验Ⅰ组的脑组织含水量为78.09±0.42％,Ⅱ组为79.01～0.66％,Ⅲ组为78.89±0.45％,Ⅳ组为79.03±0.35％,Ⅰ组脑水肿程度明显低于其它组(P<0.01)。结论 伤后早期使用大剂量白蛋白对大鼠液压颅脑损伤有明显促进神经功能恢复和减轻脑水肿的作用。     

实验性大鼠脑梗死后脑水肿规律及行为学改变

目的:探讨实验性脑梗死(cerebralinfarction,CI)后脑水肿规律和大鼠行为学改变,以指导临床脱水降颅压药物的应用。方法:参照Langa等方法制成大脑中动脉梗死模型,于术后6h、24h、48h、72h和7d采用Longa评分法、肢体对称试验评分法、Berderson评分法和平衡木评分法等4种方法进行行为学评分,并动态观察其脑含水量的变化规律。结果:对60只大鼠的研究结果显示,CI后脑组织含水量明显高于对照组,病变侧高于病变对侧,脑水肿以CI后24-72h最明显,高峰时间在CI后48h,第7d基本恢复正常。大鼠行为学改变与脑水肿的变化趋势相一致,也以CI后48h最明显。结论:大鼠CI后脑水肿规律为24-72h最明显,高峰时间在梗死后48h,7d基本恢复正常,CI后脑水肿规律与神经功能缺损的严重程度一致。     

氧化应激在大鼠液压冲击性脑损伤中的时程变化和意义

目的观察大鼠液压冲击脑损伤活性氧族(ROS)、丙二醛(MDA)、超氧化物歧化酶(SOD)以及血红素氧化酶1(HO-1)和磷酸酰胺腺嘌呤二核苷酸醌氧化还原酶1(NQO-1)表达变化,探讨氧化应激在大鼠液压冲击性脑损伤中的时程变化和意义。方法成年雄性SD大鼠56只,制作液压冲击颅脑损伤模型,分别于术后1h、6h、12h、24h、3d、7d采用分光光度法及酶学法检测ROS生成、MDA含量以及SOD活性;用干湿重法、Western blot分别测定水肿脑组织含水量及HO-1和NQO-1蛋白表达。结果与假手术组(SO组)比较,损伤组(TBI组)ROS于1h开始增加,6h急剧增加,12h达到峰值;SOD活性24h下降到最低值,MDA于24h达到峰值;HO-1和NQO-1蛋白表达均于6h开始增高,24h达到高峰,3d后降低(P0.05)。结论氧化应激性脑损伤在大鼠颅脑液压冲击伤中起着重要作用,早期调控氧化应激状态有助于减轻继发性脑损伤。     

The role of opioids in newborn pig fluid percussion brain injury

The present study was designed to characterize the relationship between cerebral opioid concentration, cerebral hemodynamics, and cerebral oxygenation following percussion brain injury in neonatal pigs. Previous research found that opioids represent a significant vasoactive component in the regulation of the neonatal piglet cerebral circulation. Anesthesized newborn (1–5 days old) pigs equipped with a closed cranial window were connected to a percussion device consisting of a saline-filled cylindrical reservoir with a metal pendulum. Brain injury of moderate severity (1.9–2.3 atm.) was produced by allowing the pendulum to strike a piston on the cylinder. Fluid percussion brain injury decreased pial arteriolar diameter (132 ± 5 to 110 ± 5 μm within 10 min). Cerebral blood flow also fell within 10 min of injury and continued to fall progressively for 3 h, resulting in a 46 ± 4% decrease. Within 30 s of brain injury, there was a transient increase in cerebral hemoglobin-O₂ saturation that was reversed to a progressive profound decrease in cerebral hemoglobin-O₂ saturation for the next 3 h, as measured by near infrared spectroscopy. CSF opioid concentrations were increased 10 min after brain injury; dynorphin showed the largest proportional increase (5.8 ± 0.9 fold). The CSF concentration for other opioids continued to increase over 180 min while the dynorphin concentration progressively decreased with time. In naloxone (1 mg/kg i.v.) pretreated piglets, the brain injury induced decrease in arteriolar diameter was attenuated (129 ± 5 to 121 ± 5 μm within 10 min). Similarly, the decrease in regional cerebral blood flow and cerebral hemoglobin-O₂ saturation observed following brain injury were also blunted by naloxone. These data show that CSF opioid concentrations increase following brain injury and that the time course and relative increase in CSF concentration vary from opioid to opioid. These data also indicate that in the immature animal, opioids contribute to arteriolar constriction, decreased cerebral blood flow, decreased cerebral oxygenation, and could play a role in causing ischemia after brain injury.     

Changes in localization of synaptophysin following fluid percussion injury in the rat brain

Traumatic brain injuries damage neurons and cause progressing dysfunctions of the brain. Synaptophysin (SYP), a major integral transmembrane protein of synaptic vesicles, provides a molecular marker for the synapse and serves as a functional marker of the brain. This study examined magnitude-dependent changes of SYP in the rat brain 2 days following low, moderate or high fluid percussion injuries and investigated time-dependent changes of SYP in the rat brain with moderate fluid percussion injury 2, 15 and 30 days after trauma using immunohistochemistry and Western blotting. SYP immunoreactivity increased in the lateral cortex and in the subcortical white matter, with increasing magnitude of injury and time after trauma. Increased SYP immunoreactivity was accompanied with degeneration of neuronal cell bodies, their processes and terminals as well as glial cell proliferations. Amounts of SYP measured by Western blotting remained unchanged in brains with moderate fluid percussion within 30 days after trauma. These findings indicate that trauma accumulates SYP at injured sites of neurons without changing SYP contents and that increased SYP immunoreactivity in the cerebral cortex following traumatic injury reflects an inhibition of synaptic vesicle transportation and dysfunction of synapses, thus providing a histological substrate for brain dysfunctions.     

液压脑损伤大鼠行为学和脑电图的研究

Objective To investigate the electroencephalogram and ethology in the rat with fluid percussion brain injury and approach its research value in the post traumatic epilepsy. Methods The change of ethology and electroencephalogram of rat in the three months after fluid percussion brain injury were observed and recorded. Results Among the survival 31 rats, there were 11 rats that appeared epilepsy. Epileptic seizure manifestation principally appeared as facial spasm, nod motion, and next limbs convulsion and turnover upspring, et al. The highest epileptic incidence rate appeared in 2 months after lateral fluid percussion brain injury. There were obvious epileptic discharges on the electroencephalogram of epileptic rats and higher wave amplitude and quicker frequency on the lead of 1～5 on the electroencephalogram of some no epileptic rats. Conclusions Post traumatic epilepsy after lateral fluid percussion brain injury in rat is similar with clinical post traumatic epilepsy. It has more research value than the other pest traumatic epileptic animal model.     

液压脑损伤大鼠行为学和脑电图的研究

Objective To investigate the electroencephalogram and ethology in the rat with fluid percussion brain injury and approach its research value in the post traumatic epilepsy. Methods The change of ethology and electroencephalogram of rat in the three months after fluid percussion brain injury were observed and recorded. Results Among the survival 31 rats, there were 11 rats that appeared epilepsy. Epileptic seizure manifestation principally appeared as facial spasm, nod motion, and next limbs convulsion and turnover upspring, et al. The highest epileptic incidence rate appeared in 2 months after lateral fluid percussion brain injury. There were obvious epileptic discharges on the electroencephalogram of epileptic rats and higher wave amplitude and quicker frequency on the lead of 1～5 on the electroencephalogram of some no epileptic rats. Conclusions Post traumatic epilepsy after lateral fluid percussion brain injury in rat is similar with clinical post traumatic epilepsy. It has more research value than the other pest traumatic epileptic animal model.     

液压脑损伤大鼠行为学和脑电图的研究

Objective To investigate the electroencephalogram and ethology in the rat with fluid percussion brain injury and approach its research value in the post traumatic epilepsy. Methods The change of ethology and electroencephalogram of rat in the three months after fluid percussion brain injury were observed and recorded. Results Among the survival 31 rats, there were 11 rats that appeared epilepsy. Epileptic seizure manifestation principally appeared as facial spasm, nod motion, and next limbs convulsion and turnover upspring, et al. The highest epileptic incidence rate appeared in 2 months after lateral fluid percussion brain injury. There were obvious epileptic discharges on the electroencephalogram of epileptic rats and higher wave amplitude and quicker frequency on the lead of 1～5 on the electroencephalogram of some no epileptic rats. Conclusions Post traumatic epilepsy after lateral fluid percussion brain injury in rat is similar with clinical post traumatic epilepsy. It has more research value than the other pest traumatic epileptic animal model.     

液压脑损伤大鼠行为学和脑电图的研究

Objective To investigate the electroencephalogram and ethology in the rat with fluid percussion brain injury and approach its research value in the post traumatic epilepsy. Methods The change of ethology and electroencephalogram of rat in the three months after fluid percussion brain injury were observed and recorded. Results Among the survival 31 rats, there were 11 rats that appeared epilepsy. Epileptic seizure manifestation principally appeared as facial spasm, nod motion, and next limbs convulsion and turnover upspring, et al. The highest epileptic incidence rate appeared in 2 months after lateral fluid percussion brain injury. There were obvious epileptic discharges on the electroencephalogram of epileptic rats and higher wave amplitude and quicker frequency on the lead of 1～5 on the electroencephalogram of some no epileptic rats. Conclusions Post traumatic epilepsy after lateral fluid percussion brain injury in rat is similar with clinical post traumatic epilepsy. It has more research value than the other pest traumatic epileptic animal model.