戊巴比妥钠和水合氯醛对窒息性心跳骤停大鼠心肺复苏后脑损伤的影响

目的 比较戊巴比妥钠和水合氯醛对窒息性心跳骤停大鼠心肺复苏后脑损伤的影响,为心肺复苏后脑保护的实验选择适宜的麻醉药物.方法 成年雄性SD大鼠160只,日龄70～95 d,体重300～400 g,随机分为2组(n=80):水合氯醛麻醉组(CH组)和戊己比妥钠麻醉组(P3组).各组再分为2个亚组(n=40):无心跳骤停对照组(CH-NR组或PB-NR组)和心跳骤停后心肺复苏组(CH-R组或PB-R组).CH组腹腔注射5%水合氯醛0.35 g/kg诱导麻醉,气管插管后行机械通气,每隔1 h腹腔注射5%水合氯醛0.1 g/kg维持麻醉;PB组腹腔注射0.35%戊巴比妥钠35 mg/kg诱导麻醉,气管插管后行机械通气,每隔1 h腹腔注射0.35%戊巴比妥钠10 mg/kg维持麻醉.CH-R组和PB-R组麻醉后建立窒息性心跳骤停后心肺复苏模型.于自主循环恢复后0.5、3、6、9、24 h(T1～5)时各处死8只大鼠,处死前15 min左侧股静脉注射2%伊文氏蓝(EB)2 ml/kg,处死后取脑组织测定脑组织含水量和EB含量.结果 与CH-NR组相比,CH-R组各时点脑组织含水量和EB含量增加(P<0.05);与PB-NR组相比,PB-R组各时点脑组织含水量和EB含量增加(P<0.05);与CH-R组相比,PB-R组T<2～5>时脑组织含水量降低(P<0.05),EB含量差异无统计学意义(P>0.05).结论 心跳骤停后心肺复苏可导致大鼠脑水肿和血脑屏障通透性增加.戊巴比妥钠较水合氯醛抑制脑水肿的程度大,而二者对血脑屏障通透性的影响无差异.     

高原烧伤大鼠脑损伤与丙二醛、超氧化物歧化酶含量变化

目的 观察高原严重烧伤延迟复苏后早期大鼠脑组织中丙二醛及超氧化物歧化酶含量变化及其与脑损伤的关系.方法 130只雄性Wistar大鼠设计高原(海拔3800 m)烧伤实验动物模型(TBSA 30%,Ⅲ度),并随机分4组:A组(高原烧伤即时复苏组)、B组(高原烧伤延迟复苏组)和C组(高原正常对照组),同时设D组(兰州地区正常对照组)(海拔1517 m).采用分光光度比色法检测脑组织中超氧化物歧化酶(SOD)的活性及丙二醛(MDA)的含量,采用干、湿重比重法测定脑组织含水量,运用末端脱氧核苷酸介导的X-dUTP缺口末端标记法(TUNEL)测定脑皮质细胞凋亡阳性细胞数.结果 A组大鼠脑组织中SOD活性于烧伤后24 h降至最低(90.45±14.78),B组大鼠腩组织中SOD活性除烧伤后12h外各时相点均低于A组(P<0.05).高原烧伤后大鼠脑组织中MDA含量即显著升高,于烧伤后12 h达最高峰(10.63±4.98),其后逐步降低至正常水平;B组大鼠脑组织中MDA含量变化趋势同A组,但于伤后7 d仍处于较高水平.脑组织含水量于伤后6 h开始升高,于24 h达高峰(71.70±2.32),于伤后7 d降至正常水平;B组变化趋势同A组.脑皮质TUNEL阳性细胞在伤后1 h即增多,于伤后24 h达高峰(233.33±16.22),于伤后7 d仍高于正常水平.结论 高原严重烧伤及延迟复苏后,脑组织中脂质过氧化物增加及超氧化物歧化酶耗竭,表明其可能参与了高原严重烧伤延迟复苏脑损伤的发生.     

硫酸镁对弥漫性脑损伤脑组织的保护作用及机制

目的 探讨硫酸镁对于弥漫性脑损伤脑组织可能的保护机制.方法 依据Marmarou's弥漫性脑损伤动物模型有改进,采用成年健康SD雄性大鼠,体质量325～375 g,共50只.其中,外伤组25只,干预组25只(两组外伤后12、24、48、72 h,1周,每组各5只).干预组应用微泵给予硫酸镁静脉注射治疗,外伤后大鼠自由进食水,按时间段处死大鼠,提取大鼠皮层脑组织,应用实时逆转录.聚合酶链反应(realtime RT-PCR)检测外伤组与干预组不同时间段ET-1 mRNA、iNOS mRNA表达,另取脑组织应用脑组织干湿重比表示脑组织含水量.结果 ET-1 mRNA表达干预组较外伤组干预组降低,应用成组t检验分析方法检验可得:6、12、24、48 h组组间差异有统计学意义(P<0.01),72 h,1周组间比较差异无统计学意(P>0.05).iNOS mRNA表达干预组较外伤组降低,干预组与外伤组相应时间组组间差异有统计学意义(P<0.01).结论 应用微泵静脉注射硫酸镁早期减少了ET-1 mRNA、iNOS mRNA的表达,从而使ET-1、iNOS、NO合成减少,减轻了脑组织缺血缺氧及对脑细胞的毒性,从而使干预组弥漫性脑损伤大鼠脑组织含水量较单纯外伤组弥漫性脑损伤大鼠脑组织含水量减少的原因.     

6%羟乙基淀粉130/0.4液体复苏对创伤性脑损伤合并失血性休克大鼠的脑保护作用

目的 探讨6%羟乙基淀粉130/0.4(6%HES 130/0.4)液体复苏对创伤性脑损伤合并失血性休克大鼠的脑保护作用.方法 健康成年雄性SD大鼠60只,体重300～350 g,随机分为5组(n=12):假手术组(S组)、模型组(M组)、生理盐水组(NS组)、6%.HES 130/0.4组(HES组)和晶体.胶体高渗透压混合液组(HHS组).分别参照Feeney改良法和Wiggers改良法制备大鼠创伤性脑损伤模型和失血性休克模型.S组仅切开头皮,钻开骨窗,不制备创伤性脑损伤和失血性休克模型;M组制备创伤性脑损伤和失血性休克模型;其余3组均制备创伤性脑损伤和失血性休克模型,并于休克60 min时开始复苏.NS组经股静脉输注3倍于放血量的生理盐水;HES组经股静脉输注等于放血量的6%HES 130/0.4;HHS组经股静脉输注等于放血量的HHS(10%HES 130/0.4与7.5%NaCl按1:1混合),各复苏组均在30 min内将液体输注完毕.实验期间记录平均动脉压(MAP),采用ELISA法测定血清S-100β蛋白浓度;于复苏180 min时取脑组织,计算脑组织含水量,采用EUSA法测定脑组织TNF-α和IL-6的含量.结果 与M组比较,NS组、HES组和HHS组复苏后MAP和脑组织含水量升高,HES组脑组织TNF-α和IL-6的含量降低,HES组和HHS组复苏后血清S-100蛋白浓度降低(P<0.05),NS组血清S-100β蛋白浓度差异无统计学意义(P>0.05);与NS组比较,HES组和HHS组复苏后MAP升高,脑组织含水量和血清S-100β蛋白浓度均降低,HES组脑组织TNF-α和IL-6的含量降低(P<0.05);与HES组比较,HHS组脑组织TNF-α和IL-6的含量升高,血清S-100β蛋白浓度升高(P<0.05),MAP差异无统计学意义(P>0.05).结论 6%HES 130/0.4液体复苏可对创伤性脑损伤合并失血性休克大鼠产生脑保护作用,且该作用强于HHS,其脑保护作用的机制可能与降低脑组织炎性反应有关.     

依达拉奉联合乌司他丁对重症急性胰腺炎大鼠脑损伤的保护作用

目的 研究依达拉奉联合乌司他丁对重症急性胰腺炎(SAP)大鼠脑损伤的保护作用.方法 100只雄性远交系大鼠随机分为10组:正常对照6h组、48 h组,SAP 6 h组、48 h组,依达拉奉处理6h组、48 h组,乌司他丁处理6h组、48 h组,依达拉奉联合乌司他丁处理6h组、48 h组;每组各10只.分别在术后第6h、48 h观察神经功能评分.采集血液、胰腺组织、脑组织标本,观察血清淀粉酶水平、脑组织伊文蓝含量、脑组织含水量、胰腺组织及脑组织镜下病理学变化.应用放射免疫法检测血清肿瘤坏死因子(TNF)-α含量,逆转录-聚合酶链反应(RT-PCR)法检测脑组织TNF-α信使核糖核酸(mRNA)含量,免疫组织化学法检测脑组织核因子(NF)-κB p65活性.结果 依达拉奉联合乌司他丁处理48 h组血清淀粉酶水平、脑组织EB含量、脑组织含水量、胰腺组织及脑组织镜下病理学评分、血清TNF-α含量、脑组织TNF-α mRNA含量及脑组织NF-κB p65活性均较依达拉奉48 h组、乌司他丁48 h组及SAP 48 h组显著降低,而神经功能评分则显著升高(P＜0.01).结论 依达拉奉联合乌司他丁对SAP大鼠脑损伤有较好的保护作用.     

戊乙奎醚预先给药对大鼠内毒素性脑损伤时NF-κB和iNOS表达的影响

目的 评价戊乙奎醚预先给药对大鼠内毒素性脑损伤时NF-κB和诱导型一氧化氮合酶(iNOS)表达的影响.方法 雄性SD大鼠105只,体重200～220 g,随机分为5组(n=21),D1组、D2组或D3组分别腹腔注射戊乙奎醚0.05、0.15、0.45 mg/kg,NS组和L组给予等容量生理盐水,10min后L组、D1组、D2组和D3组经左颈内动脉注射脂多糖150 μg,NS组给予等容量生理盐水.分别于注射戊乙奎醚后4、6和12 h处死7只大鼠,取脑组织,测定脑组织含水量、NF-κB和iNOS表达水平,光镜和电镜下观察脑组织病理学结果.结果 与NS组相比,L组、D1组、D2组和D3组脑组织含水量、NF-κB和iNOS表达增加(P<0.05);与L组相比,D1组脑组织含水量、NF-κB和iNOS表达差异无统计学意义(P0.05),D2组和D3组脑组织含水量、NF-κB和iNOS表达降低(P<0.05).D2组和D3组脑组织病理学损伤轻于L组.结论 戊乙奎醚0.15、0.45 mg/kg预先给药减轻大鼠内毒素性脑损伤的机制与抑制脑组织NF-κB和iNOS表达上调有关.     

犬严重烧伤后早期脑水肿影像学的观察对比

目的　探讨磁共振成像 (MRI)和放射性核素显像 (SPECT)在严重烧伤后早期脑水肿诊断中的价值。　方法　 2 6只犬随机分为对照组 (6只 )和致伤组 (烧伤后 6、12、18h和 2 4h组 ,每组各 5只 )。将致伤组犬制成 5 0 %TBSAⅢ度烧伤模型 ,并于伤后 6h输注质量浓度 5 0g/L葡萄糖液 ,建立严重烧伤后早期脑水肿模型。应用MRI和SPECT对各致伤组犬进行动态观察 ,将观察结果进行比较。　结果　严重烧伤后早期脑水肿模型MRI显示 ,脑形态学改变的最早时间为伤后 12h ,以弥漫性脑肿胀为变化特征 ,并随时间变化而逐渐明显。当T1WI标准化信号强度 (SIR)下降低于 10 %时 ,MRI难以发现 ;伤后 2 4hT2 WISIR增高 8.2 9% ,脑灰、白质分界模糊。SPECT扫描显示伤后 6h双侧脑组织呈弥漫性进行性核素浓集现象 ,12h以后各组脑核素含量摄取比值明显高于伤前 ,以伤后 2 4h组升高最为明显 (P <0 .0 1)。　结论　两种影像学方法联合应用 ,将明显提高烧伤后脑水肿早期诊断的敏感性和准确性     

高渗氯化钠羟乙基淀粉注射液输注对急性颅内高压伴失血性休克犬脑组织病理学及氧自由基的影响

目的 观察高渗氯化钠羟乙基淀粉40注射液(HSH)在犬急性颅内高压伴失血性休克模型中恢复循环血容量、减轻脑组织水肿和降低脑组织氧自由基含量的作用.方法 健康杂种犬20只,采用硬膜外球囊注水和动脉放血的方法复制急性颅内高压伴失血性休克模型.动物随机分为羟乙基淀粉溶液组(HES组),乳酸盐林格液组(RL组),7.5%氯化钠溶液组(HS组)和高渗氯化钠羟乙基淀粉40注射液组(HSH组),在休克后1 h分别输入相应液体.监测平均动脉压(MAP)、中心静脉压(CVP)、心率(HR)、颅内压(ICP),检测脑组织丙二醛(MDA)含量、超氧化物歧化酶(SOD)活力,脑组织标本行病理学检查.结果 复苏后4组液体均能有效地升高MAP(P<0.05),但HES组和RL组的ICP上升明显(P<0.05),复苏后2 h,HS组的MAP开始下降(P<0.05).至复苏后4 h,仅HSH组能维持理想的MAP及较低的ICP,HSH组脑组织氧自由基含量较其他组明显减少(P<0.05).病理学检查显示复苏后4 h,HSH组的脑组织损伤较其他组轻.结论 高渗氯化钠羟乙基淀粉40注射液可有效地复苏失血性休克,降低ICP及氧自由基的生成,减轻脑组织缺血/再灌注的损伤.     

严重烧伤犬早期脑水肿模型的建立

目的　建立一种严重烧伤早期犬的脑水肿模型。　方法　采用凝固汽油体表烧伤制成 5 0 %TBSAⅢ度烧伤犬模型。随机将实验组分为单纯烧伤组 ,乳酸钠液组和葡萄糖液组 ,于伤后 6、12、18、2 4h各时相点观察大体形态及镜下 (光镜 ,电镜 )组织变化 ,计算脑含水量 ,用99锝一半双胱乙酯 (99TCm-ECD)观察血脑屏障的变化。　结果　伤后 6h犬脑即出现早期脑水肿的组织学改变 ,部分毛细血管内皮及血管周围星形细胞肿胀 ,毛细血管内皮细胞、神经细胞及轴突不同程度的缺血坏死。随着伤后时间的延长 ,这种改变逐渐明显。实验各组伤后 6h脑含水量与对照组比较即有增加 ,而以葡萄糖液组伤后 2 4h增高最为显著 (P <0 .0 1)。脑核素显像显示单纯烧伤组及葡萄糖液组伤后 6h开始即出现逐渐明显的脑组织核素浓集。　结论　严重烧伤早期犬脑水肿模型的建立 ,为临床对严重烧伤后脑水肿的防治研究提供了形态学基础 ,是一种具有较好稳定性和可重复性的脑水肿动物模型     

氯胺酮对脑冷冻伤后自由基和脑水肿的影响

目的 探讨N-甲基-D-天门冬氨酸(N—methyl—D-aspartate，NMDA)受体非竞争性拮抗药氯胺酮对鼠脑冷冻伤后脑内超氧化物歧化酶(superoxide dismutase，SOD)、丙二醛(malondialdehyde，MDA)和脑水肿的影响。方法 49只SD大鼠随机分为假手术组、未治疗组和氯胺酮治疗组。采用液氮局部冷冻左侧鼠脑30s制作冷冻伤模型，分别于2、6、24h处死动物后，用分光光度法测10％脑组织匀浆中SOD活性和MDA产量。结果 脑组织含水量在冷冻伤后显著升高，并随时间延长而加重。氯胺酮治疗后脑组织含水量没有明显减少；脑组织SOD活性在2、6h高于未治疗组，但24h后SOD活性无显著差异。MDA含量比未治疗组在相应时段显著减少。结论 自由基是脑水肿形成的重要因素，氯胺酮能减轻冻伤脑组织中SOD活性的抑制，减少MDA生成，但对脑水肿无明显治疗作用。     

Effects of magnesium sulfate on traumatic brain edema in rats

svarietyofneuroprotectiveagentshavebeensynthesized .However ,besidessomeagentspresentlybeingevaluatedinclinicaltrails ,mostofthesecompoundshavelimitedclinicalusebecauseofneurotoxicityandbehavioralsideeffects .Recently ,severalstudiesdemonstratedthattraumaticinjurytothebraincausesadecreaseinmagnesiumconcentrationcorrelatedwithinjuryseverity .1Sincethen ,moreandmoreattentionhasbeen paidtoMgSO4 foritsneuroprotectiveeffects .Magnesiumsulfatehasbeenwidelyusedinclinicalpracticeforalmost 10 0 years.…     

高渗氯化钠羟乙基淀粉40注射液对大鼠全身高温模型血脑屏障通透性的影响

目的 观察高渗氯化钠羟乙基淀粉40注射液对大鼠全身高温模型血脑屏障(blood brain barrier.BBB)通透性的影响并探讨其作用机制.方法 成年雄性sD大鼠60只,随机分为正常对照组(C组),高温组(HT组),高温林格组(RL组),高温羟乙基淀粉林格组(HRL组),高温高渗氯化钠羟乙基淀粉组(HSH组),C组大鼠置:P(25-26)℃的环境中4 h,其余各组大鼠置于36 ℃具备生物氧供给的加温舱中3 h达到肛温(41.42)℃.加温开始30 min内根据实验分组输入相应的液体,3 h后出舱在室温下降温,加温期间监测肛温、平均动脉(mean arterial blood pressure,MAP)和动脉血气.采用伊文思兰(evans blue,EB)法检测大鼠血脑屏障的通透性,干湿法检测大鼠脑组织的百分含水量.结果 与C组相比,其他各组大鼠的脑百分含水量、肛温和EB值均有显著的升高(P<0.01).但HSH组升高值较其余3组为低(P<0.01).各实验组大鼠的MAP、pH、PaO2、Pa-CO2、Hct与C组相比差异有统计学意义(P<0.05).Na+、K+在HT组和HSH组明显升高(P相似文献   

Effects of crystalloid-colloid solutions on traumatic brain injury

The purpose of this study was to compare the effects of crystalloid and crystalloid-colloid solutions administered at different times after isolated traumatic brain injury. Male Sprague-Dawley rats were randomized to receive one of three intravenous treatments (4 mL/kg body weight) at 10 min or 6 h after moderate traumatic brain injury. Treatments included hypertonic saline, hypertonic albumin, and normal albumin. Moderate injuries were produced using the controlled cortical impact injury model set at 2.0 mm, 4.0 m/sec, and 130 msec. Tissue damage and cerebral edema were measured to evaluate the effect of treatments for traumatic brain injury. Blood brain barrier permeability was assessed at different time points after injury to identify a mechanism for treatment effectiveness. Injury volume was the smallest for animals treated with hypertonic albumin at 6 h after injury compared to all other treatments and administration times. Ipsilateral brain water content was significantly attenuated with immediate normal saline-albumin treatment. The presence of colloid in the infusion solutions was associated with an improvement in tissue damage and edema following isolated head injury while hypertonic saline alone, when given immediately after injury, worsened tissue damage and edema. When hypertonic saline was administered at 6 h after injury, tissue damage and edema were not worsened. In conclusion, the presence of colloid in solutions used to treat traumatic brain injury and the timing of treatment have a significant impact on tissue damage and edema.     

Effects of magnesium sulfate on traumatic brain edema in ats

OBJECTIVE: To investigate the effects of magnesium sulfate on traumatic brain edema and explore its possible mechanism. METHODS: Forty-eight Sprague-Dawley (SD) rats were randomly divided into three groups: Control, Trauma and Treatment groups. In Treatment group, magnesium sulfate was intraperitoneally administered immediately after the induction of brain trauma. At 24 h after trauma, total tissue water content and Na(+), K(+), Ca(2+), Mg(2+) contents were measured. Permeability of blood-brain barrier (BBB) was assessed quantitatively by Evans Blue (EB) dye technique. The pathological changes were also studied. RESULTS: Water, Na(+), Ca(2+) and EB contents in Treatment group were significantly lower than those in Trauma group (P<0.05). Results of light microscopy and electron microscopy confirmed that magnesium sulfate can attenuate traumatic brain injury and relieve BBB injury. CONCLUSIONS: Treatment with MgSO4 in the early stage can attenuate traumatic brain edema and prevent BBB injury.     

Combined hemorrhagic shock and head injury: effects of hypertonic saline (7.5%) resuscitation

Hypertonic saline resuscitation was compared to isotonic fluid resuscitation in a large animal model combining hemorrhagic shock with head injury. Sheep were subjected to a freeze injury of one cerebral hemisphere as well as 2 hours of hypotension at a mean arterial pressure (MAP) of 40 mm Hg. Resuscitation was then carried out (MAP = 80 mm Hg) for 1 hour with either lactated Ringer's (LR, n = 6) or 7.5% hypertonic saline (HS, n = 6). Hemodynamic parameters and intracranial pressure (ICP) were followed. At the end of resuscitation brain water content was determined in injured and uninjured hemispheres. No differences were detected in cardiovascular parameters; however, ICPs were lower in animals resuscitated with HS (4.2 +/- 1.5 mm Hg) compared to LR (15.2 +/- 2.2 mm Hg, p less than 0.05). Additionally, brain water content (ml H2O/gm dry weight) in uninjured brain hemispheres was lower after HS resuscitation (HS = 3.3 +/- 0.1; LR = 4.0 +/- 0.1; p less than 0.05). No differences were detected in the injured hemispheres. We conclude that hypertonic saline abolishes increases in ICP seen during resuscitation in a model combining hemorrhagic shock with brain injury by dehydrating areas where the blood-brain barrier is still intact. Hypertonic saline may prove useful in the early management of multiple trauma patients.     

Breakdown of the blood-brain barrier after fluid percussion brain injury in the rat: Part 2: Effect of hypoxia on permeability to plasma proteins.

Clinical studies have demonstrated that hypoxia after severe brain injury is common and significantly worsens neurologic outcome. We have, therefore, developed a rat model of posttraumatic hypoxic injury in order to identify the pathophysiologic responses after head injury that are worsened by this secondary insult. We examined the effect of hypoxia after brain injury on permeability of the blood-brain barrier to plasma proteins. Animals were divided into two experimental groups: group I (impact alone) and group IH (impact plus hypoxia). Rats were subjected to a lateral fluid percussive brain injury (4.8-5.2 atm). Animals in group IH were exposed to hypoxic conditions (10% O2) for 45 min immediately after injury. In each group, vascular permeability to endogenous immunoglobulins (IgG) and to horseradish peroxidase (HRP) was examined at the light microscopic level. IgG was immunolocalized in brain sections at 1-24 h after injury. In other studies, HRP was given i.v. either before impact or 10 min before killing. Permeability to this protein was assessed at 1-72 h after injury. The distribution of extravasated proteins was similar between the experimental groups at 1 h postinjury. Pronounced abnormal permeability to IgG and HRP (given before impact) occurred in discrete regions throughout both the ipsilateral and contralateral hemispheres. By 6 h after injury, a differential response of the blood-brain barrier was noted between groups I and IH. Widespread leakage of proteins was observed in the injured hemisphere in group IH. This finding was in sharp contrast to group I, in which extravasated proteins remained more localized in the injured hemisphere. The time course for reestablishment of the blood-brain barrier to HRP (given before killing) was determined. The impact site remained permeable to HRP up to at least 72 h postinjury within groups I and IH. In group I, the blood-brain barrier was reestablished in the parasagittal cortex and deep cortical layer by 6 h postinjury. In contrast, the blood-brain barrier in group IH was not restored in similar brain regions until 24 h postinjury. These studies demonstrate that (1) hypoxia after brain injury exacerbates the regional breakdown of the blood-brain barrier to circulating proteins, (2) this influence of hypoxia on permeability is not apparent immediately after injury but rather is expressed at 6 h after injury, and (3) hypoxia after traumatic brain injury delays recovery of the blood-brain barrier. These findings suggest that secondary posttraumatic hypoxia contributes to the vascular pathogenesis of brain injury.     

Brain levels of polyethylene glycol-conjugated superoxide dismutase following fluid percussion brain injury in rats.

Polyethylene glycol-conjugated superoxide dismutase (PEG-SOD) is being explored as an agent to reduce oxygen radical-mediated damage following brain injury. Yet little is known concerning the site of action of IV-administered PEG-SOD or the capacity of this conjugated enzyme to enter the brain. The purpose of this study was to determine the brain content of PEG-SOD in normal and fluid percussion injured rats. The fluid percussion device was attached over the right parietal cortex and a moderate (2.0 atm) intensity injury was produced. PEG-SOD was conjugated with 125I and given (2000 U/kg, 5 microCi/kg) to rats either 30 min before or 30 min after brain injury. Another group received [125I]PEG-SOD but was not injured. Plasma and left and right brain hemispheres were counted for [125I]PEG-SOD. Plasma levels of [125I]PEG-SOD declined similarly in all three groups during the 90-min period after IV administration. Brain [125I]PEG-SOD was low in control animals (0.034 U/g wet wt). In animals given PEG-SOD after injury the brain level was elevated sixfold in both the left and right hemispheres, compared to control. In rats given the drug before injury, [125I]PEG-SOD was 10 times control level in the right hemisphere, which is the side on which the injury device is attached, and 6 times control level in the left hemisphere. We conclude that traumatic brain injury produces an increase in brain PEG-SOD. The exact cellular site of the increased brain PEG-SOD remains to be clarified.     

The Effect of the Reduction of Colloid Reduction of Oncotic Pressure, with and without Reduction of Osmolality, on Post-traumatic Cerebral Edema

Background: It has been asserted that reduction of colloid oncotic pressure (COP) can aggravate traumatic brain edema. To explore this issue, the authors measured the effect of COP reduction, with and without a simultaneous decrease in osmolality, on the development of brain edema after fluid percussion injury (FPI).

Methods: Isoflurane-anesthetized Wistar rats received a 2.7-atm right parasagittal FPI followed by isovolemic exchange with (1) normal saline (NS); (2) half-normal saline (0.5 NS); (3) whole blood (WB); or (4) hetastarch (Hespan, Dupont). Shed blood (16 ml) was replaced with donor erythrocytes suspended in the study fluid. The WB group received heparinized fresh donor WB. Central venous pressure was maintained with additional study fluid as required. The specific gravity (SG) of the cortex and subcortex near the impact site was determined 4.5 h after FPI. The water content of the hemispheres was also determined using the wet-dry method. To define the status of the blood-brain barrier in the non-FPI hemisphere, two additional groups (FPI, non-FPI) were studied. Both groups received 30 mg/kg Evans' blue and NS at 4 ml/kg1/h sup -1. Four hours after FPI, the concentration of Evans' blue in the hemispheres was determined.

Results: After exchange, COP (mmHg +/- SD) decreased in the NS (9.6 +/- 2.1) and 0.5 NS (8.5 +/- 0.5) groups and was unchanged in the WB (16.7 +/- 3.3) and hetastarch (18.9 +/- 1.1) groups. Osmolality was unchanged in the WB group (295 +/- 5 mOsm/kg), increased in the NS (304 +/- 3 mOsm/kg) and hetastarch (306 +/- 2 mOsm/kg) groups, and was decreased in the 0.5 NS group (261 +/- 6 mOsm/kg). The Evans' blue data indicated that FPI resulted in blood-brain barrier damage in both hemispheres. In all four exchange groups, the SG of both cortical and subcortical tissue was less (indicating greater water content) in the impact hemisphere than in the nonimpact hemisphere. The SG was less in both hemispheres, although it was less in both hemispheres in the NS and 0.5 NS groups than in the WB and hetastarch groups. The lowest SG values were observed in the 0.5 NS group. The wet-dry water content determinations yielded a similar pattern of edema formation.     

Spatial and temporal profile of apoptosis following lateral fluid percussion brain injuury

OBJECTIVE: To investigate the spatial and temporal profile of neural cell apoptosis following traumatic brain injury (TBI). METHODS: In addition to morphological evidence of apoptosis, TUNEL histochemistry assay was used to identify DNA fragmentation in situ at both light and electron microscopic levels, whereas characteristic internucleosomal DNA fragmentation of apoptosis was demonstrated by DNA gel electrophoresis. RESULTS: Using TUNEL method, we detected massive cells with extensive DNA fragmentation in different regions of the brains of rats subjected to experimental traumatic brain injury. Compared with the sham controls, in the injured cortex, the apoptotic cells were detectable for up to 24 h and reached a peak at 1 week after injury. The number of apoptotic cells in the white matter h ad a significant increase as early as 12 h after injury and peaked at 1 wee k. The number of apoptotic cells increased in the hippocampus at 72 h, whereas i n the thalamus, the peak of apoptotic cells was at 2 weeks after injury. The number of apoptotic cells in most regions returned to sham values 2 months after in jury. Gel electrophoresis of DNA extracted from affected areas of the injured br ain revealed only internucleosomal fragmentation at 185-bp intervals, a feature originally described in apoptotic cell death. And no DNA ladder was detectable in the cortex and hippocampus contralateral to the injured hemisphere. CONCLUSIONS: These data suggest that in addition to the well described necrotic cell death, a temporal course of apoptotic cell death is initiated after brain trauma in selected brain regions.