异丙酚、咪唑安定和硫喷妥钠对鼠局灶脑缺血/再灌注后氨基酸堆积的影响

目的观察异丙酚、咪唑安定和硫喷妥钠对鼠局灶脑缺血/再灌注后缺血部位氨基酸类神经递质含量的影响.方法采用大脑中动脉(MCA)内线栓法诱发局灶脑缺血.雄性SD大鼠随机分为5组,每组6～7只.缺血组仅经历3 h MCA阻塞;再灌注组经历3 h MCA阻塞和3 h再灌注;三个用药组于再灌注前即刻分别腹腔内注射异丙酚、咪唑安定和硫喷妥钠50 mg@kg-1,再灌注3h后,处死鼠,迅速取脑,用高效液相色谱法测脑组织兴奋性氨基酸类含量.结果异丙酚、咪唑安定明显减少再灌注期缺血部位门冬氨酸、谷氨酸堆积;异丙酚增强,而咪唑安定减小GABA堆积;硫喷妥钠无明显作用.结论异丙酚和咪唑安定可能通过加快再灌注期兴奋性氨基酸的清除而产生脑保护效应.     

异丙酚、硫喷妥钠对大鼠脑局灶性缺血/再灌注损伤对血脑屏障通透性改变的影响

目的 比较异丙酚和硫喷妥钠对大脑局灶性缺血／再灌注损伤中血脑屏障（ＢＢＢ）通 性变化及神经病理学的影响。方法 ６０只成年大鼠随机分为５组,均采用尼龙线栓堵左侧大脑中动脉的方法建立暂时性局灶性脑缺血模型：对照组（ＭＣ组）不用全麻药;异丙酚预防组（ＭＰ１组）及硫喷妥钠预防组（ＭＴ１组）,在制作大脑中动脉闭塞模型前３０ｍｉｎ分别静脉注射异丙酚２０ｍｇ／ｋｇ或２．５％硫喷妥钠溶液４０ｍｇ／ｋｇ,继之以异丙     

脂氧素A4对局灶性脑缺血再灌注大鼠血脑屏障通透性的影响

目的 探讨脂氧素A4对局灶性脑缺血再灌注大鼠血脑屏障通透性的影响.方法 健康成年雄性SD大鼠54只,体重200～250 g,随机分为3组(n=18):假手术组(S组)、局灶性脑缺血再灌注组(I/R组)和脂氧素A4组(L组).采用改良线栓法制备大鼠局灶性脑缺血再灌注损伤模型,阻断右侧大脑中动脉缺血2 h后行再灌注.L组缺血即刻右侧侧脑室注射脂氧素A4 100 ng,S组和I/R组右侧侧脑室注射等容量生理盐水5 μl.于再灌注24 h时行神经功能缺陷评分,静脉注射2%伊文斯蓝4 ml/kg,1 h后处死大鼠取脑,测定右侧脑水含量和伊文斯蓝含量,检测脑皮质基质金属蛋白酶9(MMP-9)的表达.结果 与S组比较,I/R组和L组神经功能缺陷评分、脑水含量和伊文斯蓝含量升高,脑皮质MMP-9表达上凋(P＜0.05或0.01);与I/R组比较,L组神经功能缺陷评分、脑水含量和伊文斯蓝含量降低,脑皮质MMP-9表达下调(P＜0.01).结论 脂氧素A4可降低血脑屏障通透性,减轻脑水肿,促进局灶性脑缺血再灌注损伤大鼠的神经功能恢复,其机制与抑制MMP-9表达上调有关.     

咪唑安定预防全麻知晓的初步观察

咪唑安定具有较好的顺行性遗忘作用，笔者在全麻硫喷妥钠或异丙酚诱导前，给予小剂量咪唑安定。并与单纯硫喷妥钠诱导或异丙酚诱导进行比较，观察面罩吸氧期、手术中及清醒拔管期病人的知晓、回忆情况。今报告如下。     

缬沙坦预先给药对小鼠局灶性脑缺血再灌注损伤的保护作用

目的探讨血管紧张素Ⅱ1型受体(AT1)阻断剂缬沙坦预先给药对小鼠脑缺血再灌注损伤的保护作用。方法36只雄性C57BL/6J小鼠随机分为两组,每组18只,处理组(V组)将缬沙坦溶于2.5%NaHCO3 100μl,以微量注射泵2 mg·kg-1·d-1泵入腹腔至实验结束,对照组(C组)仅予2.5% NaHCO3 100μl在相同时间以相同速率泵注。给药第10天以线栓法建立局灶性脑缺血再灌注损伤模型,缺血1 h后拔出线栓,再灌注23 h。以激光多普勒血流探测仪测定缺血前10 min、缺血即刻、缺血10、30、50 min、再灌注10、30、60 min时的局部脑血流。在应用缬沙坦前即刻、缺血前10 min、再灌注10min用尾袖法测量平均动脉压。再灌注23 h后行神经功能损害评分。处死小鼠后,测定脑梗塞灶面积和脑含水量。结果两组小鼠3个时点的平均动脉压比较差异无统计学意义(P>0.05)。与C 组比较,V组脑梗塞灶面积减小,死亡率降低,神经功能损害评分降低,脑含水量减少,再灌注后V组梗塞灶中央区和半暗区局部脑血流升高(P<0.05)。结论预先应用AT1受体阻断剂缬沙坦可改善局部脑血流,减轻小鼠局灶性脑缺血再灌注损伤。     

异丙酚对大鼠局灶性脑缺血/再灌注后细胞凋亡的影响

目的：观察异丙酚对大鼠局灶性脑缺血／再灌注后细胞凋亡的影响。方法：雄性SD大鼠，采用可逆性大脑中动脉内线栓法建立局灶性脑缺血／再灌注模型。缺血2h，再灌注2h后断头取脑，采用脱氧核昔酸末端转移酶介导的DNA原位末端标记技术检测细胞凋亡变化。HE染色，光镜观察细胞结构的改变。结果：光镜检查发现，异丙酚组细胞肿胀坏死明显减轻，异丙酚可显著减少脑缺血／再灌注后神经细胞的调亡。结论：静脉麻醉药异丙酚具有拮抗大鼠局灶性脑缺血／再灌注损伤作用，对缺血／再灌注的神经细胞有明显的保护作用。     

异丙酚对大鼠脑缺血再灌注损伤的保护作用

目的研究异丙酚对大鼠脑缺血再灌注损伤的保护作用及其机制。方法SD大鼠90 只,体重290-310 g,随机分成3组,异丙酚组(P组,n=42);生理盐水组(NS组,n=42);假手术组(S 组,n=6)。NS、P组采用线栓法(尼龙线栓插入颈外动脉)制备局灶性脑缺血再灌注损伤模型,P组在缺血前10min腹腔注射异丙酚10mg/100 g,NS组给予等量生理盐水;S组只作切口,不作颈总动脉插线。P和NS组分别在再灌注即刻、2 h、5 h、11 h、23 h、71 h、1周,处死6只大鼠,断头取脑,S组于再灌注11 h断头取脑,制作脑片,计算脑梗塞体积比;测定缺血半影区GLUT1 mRNA及蛋白表达水平。结果与S组相比,P、NS组再灌注各时点脑梗塞体积比增大;P组再灌注各时点梗塞体积小于NS组(P<0.05或0.01)。P、NS组缺血半影区GLUT1 mRNA及蛋白表达从再灌注即刻开始升高,23 h达高峰;P组再灌注各时点缺血半影区均高于NS组,P、NS组GLUT1 mRNA及蛋白表达再灌注各时点均高于S组(P<0.05或0.01)。结论异丙酚对大鼠缺血再灌注损伤有一定保护作用,上调缺血半影区GLUT1的表达是其机制之一。     

异丙酚预先给药对大鼠脑缺血再灌注时内质网应激性细胞凋亡的影响

目的 评价异丙酚预先给药对大鼠局灶性脑缺血再灌注损伤时内质网应激性细胞凋亡的影响.方法 健康成年雄性SD大鼠80只,体重240～280 g,采用随机数字表法,将大鼠随机分为4组(n=20):假手术组(S组);局灶性脑缺血再灌注组(FCIR组)采用阻塞大脑中动脉4h恢复灌注的方法制备大鼠局灶性脑缺血再灌注模型;异丙酚预先给药组(P组)于缺血前30 min股静脉泵注异丙酚12mg·kg-1·h-1至缺血15min;脂肪乳预先给药组(Ⅰ组)给予脂肪乳1.2 ml·kg-1·h-1.于再灌注6h时各组随机取10只大鼠采用Longa评分法行神经功能缺陷评分(NDS),处死取左侧大脑,用干湿重法测定脑含水量,余10只大鼠处死后取左侧海马,采用Western blot法检测C/EBP环磷酸腺苷反应元件结合转录因子同源蛋白(CHOP)、Bcl-2和活化型caspase-3蛋白的表达水平.结果 与S组比较,FCIR组再灌注6h时NDS评分和脑含水量升高,CHOP和活化型caspase-3蛋白表达上调,Bcl-2蛋白表达下调,P组NDS评分升高(P＜0.05);与FCIR组比较,P组再灌注6h时NDS评分和脑含水量降低,CHOP和活化型caspase-3蛋白表达下调,Bcl-2蛋白表达上调(P＜0.05),Ⅰ组各指标差异无统计学意义(P＞0.05).结论 异丙酚可通过抑制内质网应激介导的细胞凋亡减轻大鼠局灶性脑缺血再灌注损伤.     

几种不同药物对大鼠全脑缺血再灌注时大脑c－fos基因表达影响的实验研究

新近研究表明，ｃ－ｆｏｓ基因表达在脑缺血再灌注损伤机制中发挥着第三信使的重要作用。应用ＲＮＡ分子杂交方法，研究尼莫地平等药物对全脑缺血再灌注时大脑ｃ－ｆｏｓ基因表达的影响，以期探讨脑缺血再灌注损伤保护的分子基因机制。缺血前３０分钟静注尼莫地平、安定、硫喷妥钠和吸入异氟醚、安氟醚，全脑缺血再灌注各３０分钟，提取大脑总ＲＮＡ，与ｃ－ｆｏｓＣＤＮＡ探针分子杂交，经过自显影，检测该时点ｃ－ｆｏｓ基因ｍＲＮＡ水平。结果显示：尼莫地平、安定、异氟醚能显著抑制缺血３０分钟再灌注３０分钟ｃ－ｆｏｓ基因表达，而硫喷妥钠、安氟醚对该时点该基因表达无影响。实验提示：ｃ－ｆｏｓ基因参与全脑缺血再灌注损伤保护的分子基因机制。本大学第二医院麻醉科     

异丙酚对大鼠局灶性脑缺血再灌注时NF-κB活化和Bcl-2、Caspase-3基因表达的影响

目的观察异丙酚对大鼠局灶性脑缺血再灌注时NF-κB的活化和Bcl-2、Caspase-3基因表达的影响,并探讨其脑保护的机制。方法 90只雄性Wistar大鼠,采用大脑中动脉线栓法建立局灶性脑缺血再灌注模型,随机将大鼠分为假手术组、缺血再灌注组(I／R)和异丙酚组(缺血前10 min腹腔注射异丙酚100 mg·kg-1)。各组根据再灌注时间不同又分为缺血2 h再灌注2、3、6、12、24、72 h亚组, 每亚组各5只大鼠。于再灌注2、6、12、24 h,采用免疫组织化学染色法分析NF-κB的移位,蛋白质印迹法检测NF-κB的表达量。于再灌注3、6、24、72 h,采用原位杂交法法检测脑组织Bcl-2 mRNA、Caspase-3 mRNA的表达。于再灌注24 h作神经功能缺陷评分及苏木精-伊红(HE)染色观察缺血皮层组织形态学变化。结果与假手术组比较,I／R组缺血侧大脑皮层NF-κB于再灌注2-24 h明显从细胞浆移位于细胞核内,NF-κB和Bcl-2 mRNA、Caspase-3 mRNA的表达量增加(P<0．01),大鼠神经功能缺陷评分升高(P<0．01),组织形态学观察可见皮层水肿、淤血,神经元变性坏死。与I／R组比较,异丙酚组NF- κB从细胞浆向细胞核的移位被抑制,NF-κB和Caspase-3 mRNA的表达量减少(P<0．05),Bcl-2 mRNA 的表达量增加(P<0．05),神经功能缺陷评分降低(P<0．05),缺血大脑皮层组织形态学损伤减轻。结论异丙酚的脑保护作用可能与其抑制NF-κB的活化,上调Bcl-2基因和下调Caspase-3基因的表达,从而抑制神经组织细胞凋亡有关。     

异丙酚对大鼠脑缺血再灌注后脑细胞凋亡和Bcl-2、Caspase-3蛋白表达的影响

脑缺血再灌注后脑损伤的发病机制较复杂,其所致病理损伤包括细胞坏死和凋亡。细胞凋亡与脑缺血再灌注损伤关系密切,是神经元迟发性死亡的主要形式。研究提示与凋亡密切相关的Bcl-2、Caspase-3蛋白等参与了这种迟发性死亡,它们表达的量决定了细胞的生存。本实验采用流式细胞仪、     

N-myc下游调节基因2在七氟醚预处理减轻大鼠局灶性脑缺血再灌注损伤中的作用

目的 评价N-myc下游调节基因2(NDRG2)在七氟醚预处理减轻大鼠局灶性脑缺血再灌注损伤中的作用.方法 健康雄性成年SD大鼠48只,体重280～320 g,采用随机数字表,将大鼠随机分为3组(n=16):假手术组(S组)、脑缺血再灌注组(I/R组)和七氟醚预处理组(Sev组).采用大脑中动脉阻断法制备大鼠局灶性脑缺血再灌注模型.大鼠吸入2％七氟醚lh,每天1次,连续5d行七氟醚预处理.Sev组于七氟醚预处理结束后24h制备局灶性脑缺血再灌注模型.再灌注24h时行神经功能评分,随后处死大鼠,取脑组织,测定脑梗死体积百分比,采用Western Blot法测定缺血半暗带区NDRG2和活化的Caspase-3的表达,采用免疫组织荧光测定缺血半暗带区NDRG2的表达及定位.结果 与S组比较,I/R组和Sev组脑梗死体积百分比升高,神经功能评分降低,脑组织缺血区半暗带NDRG2和活化的Caspase-3表达上调(P＜0.05);与I/R组比较,Sev组脑梗死体积百分比降低,神经功能评分升高,脑组织缺血区半暗带NDRG2和活化的Caspase-3表达下调(P＜0.05).Sev组核内NDRG2阳性染色较I/R组减浅.结论 七氟醚预处理可能通过抑制脑组织NDRG2的表达、活性和细胞凋亡,从而减轻大鼠局灶性脑缺血再灌注损伤.     

Isoflurane provides long-term protection against focal cerebral ischemia in the rat

BACKGROUND: Long-term neuroprotection by isoflurane has been questioned. The authors examined factors in experimental models potentially critical to definition of enduring isoflurane neuroprotection. METHODS: Rats were prepared for temporary middle cerebral artery occlusion (MCAO). Pericranial normothermia was maintained. Neurologic deficits (range, 0-48; 0=no deficit) and cerebral infarct volumes were measured. In experiment 1, rats underwent 50 or 80 min MCAO while awake or anesthetized with 1.8% isoflurane. Blood pressure was controlled with phenylephrine. Outcome was evaluated 2 weeks later. In experiment 2, rats underwent 50 min MCAO while awake or anesthetized with isoflurane, with outcome evaluated 8 weeks later. In experiment 3, rats underwent 50 min MCAO while awake or anesthetized with isoflurane and 2 weeks recovery. Effects of phenylephrine and the mitochondrial adenosine triphosphate-sensitive K channel antagonist 5-hydroxydecanoate were studied. In experiment 4, isoflurane-anesthetized rats underwent 50 min MCAO with permanent or temporary common carotid artery occlusion, with outcome evaluated 2 weeks later. RESULTS: In experiment 1, isoflurane reduced neurologic deficit (median+/-interquartile range; awake vs. isoflurane: 11+/-12 vs. 8+/-6 for 80 min and 13+/-4 vs. 3+/-9 for 50 min; P=0.0006) and infarct size (160+/-97 vs. 84+/-62 mm for 80 min and 169+/-78 vs. 68+/-61 mm for 50 min; P<0.0001). In experiment 2, isoflurane protection persisted at 8 weeks after ischemia. In experiment 3, there was no effect of phenylephrine or 5-hydroxydecanoate. In experiment 4, permanent common carotid ligation increased infarct size threefold versus temporary occlusion. CONCLUSIONS: Isoflurane repeatedly improved long-term neurologic and histologic outcome from focal ischemia independent of ischemia duration, perfusion pressure, or pretreatment with 5-hydroxydecanoate.     

Effect of propofol on pathologic time-course and apoptosis after cerebral ischemia-reperfusion injury

Background: Propofol has been demonstrated to ameliorate cerebral ischemic injury and attenuate changes in multiple links of molecular reaction included in the paths to apoptosis. The experiment was aimed to evaluate whether propofol neuroprotection was mediated through the ability to regulate pathologic time-course of apoptosis.
Methods: The effect of propofol given at a series of time points during ischemia–reperfusion period was determined using an intraluminal middle cerebral artery occlusion model in rats. The morphological changes of apoptosis under different duration of ischemia were detected by terminal deoxynucleotidyl transferase (TdT)-mediated dUTP-biotin in situ nick labeling staining, and the effect of propofol on apoptosis was observed. The expression of anti-apoptotic protein bcl-2 in post-ischemia neurons and the influence of propofol was analyzed by immunochemistry staining.
Results: Propofol attenuated neurological deficit, reduced infarct volumes, when given prior the onset of ischemia, during ischemia or 3 h after reperfusion. Apoptosis obviously appeared at 6 h post-reperfusion preceded by 90 min ischemia, rose to the maximum value at 24 h post-reperfusion and gradually diminished after 3 days reperfusion. Propofol inhibited apoptotic morphological changes between 6 h and 3 days post-reperfusion. Propofol enhanced the expression of anti-apoptotic protein bcl-2 in post-reperfusion neurons.
Conclusions: The pathologic outcome of focal cerebral ischemia–reperfusion injury was displayed by co-existence of apoptosis and necrosis. A short duration of ischemia induced apoptosis. The therapeutic window for propofol initiated before the onset of ischemia and lasted until early stage of reperfusion. The neuroprotection of propofol might be attributed to the inhibition of apoptosis.     

异氟醚预处理对大鼠局灶性脑缺血再灌注时TLR4和MyD88表达的影响

目的 评价异氟醚预处理对大鼠局灶性脑缺血再灌注时Toll样受体4(TLR4)和髓样分化因子88(MyD88)表达的影响.方法 雄性成年SD大鼠54只,体重250～300 g,随机分为3组(n=18):假手术组(S组)仅分离血管,不留置线栓;脑缺血再灌注组(IR组)采用线栓法制备大鼠局灶性脑缺血再灌注模型,缺血2 h,再灌注24 h;异氟醚预处理(IP组)吸入2%异氟醚,1h/d,连续5 d,处理结束后24 h时制备大鼠局灶性脑缺血再灌注模型.再灌注24 h时进行神经功能缺陷评分,然后每组处死3只大鼠,测定脑梗死体积.分别于再灌注24、48和72 h时,处死5只大鼠,取右侧大脑缺血部位额叶皮质,采用Western blot法测定TLR4、MyD88和NF-κB的表达水平.结果 与S组比较,IR组和IP组神经功能缺陷评分升高,脑梗死体积增大,IR组TLR4、MyD88和NF-κB的表达均上调,IP组MyD88和NF-κB的表达上调(P＜0.05);与IR组比较,IP组神经功能缺陷评分降低,脑梗死体积减小,TLR4、MyD88和NF-κB的表达均下调(P＜0.05).结论 异氟烷预处理可通过抑制脑组织TLR4和MyD88的表达,减轻炎性反应,从而减轻大鼠局灶性脑缺血再灌注损伤.     

异丙酚对大鼠局灶性脑缺血再灌住损伤时蛋白激酶B活性的影响

目的 评价异丙酚对大鼠局灶性脑缺血再灌住损伤时蛋白激酶B(Akt)活性的影响,以探讨异丙酚脑保护作用的机制.方法 健康SD大鼠90只,体重260～300 g,雌雄不拘,随机分为5组(n=18):假手术组(S组);局灶性脑缺血再灌注组(IR组)、P1-3组阻断大脑中动脉2 h,开放22 h,制备大鼠局灶性脑缺血再灌注模型,分别于再灌注前3 min至再灌注5 min时经股静脉输注生理盐水2.5ml、异丙酚1、2、5 mg/kg(异丙酚采用生理盐水稀释至2.5 ml).于再灌注22 h时行神经行为学评分;测定大鼠脑梗死质量、免疫组化法检测大鼠脑组织caspase-3表达、Western blot法检测Akt活性.结果 与S组比较,再灌注22 h时IR组、P1-3组神经行为学评分、脑梗死质量比升高,脑组织caspase-3表达上调,P1组和P2组Akt活性升高,IR组和P3组Akt活性降低(P<0.05);与IR组比较,P1组和P2组大鼠神经行为学评分,脑梗死质量比降低,腩组织caspase-3表达下调,Akt活性升高(P<0.05).结论 静脉输注异丙酚1、2 mg/kg可通过升高Akt活性,抑制脑组织细胞凋亡,减轻大鼠局灶性脑缺血再灌注损伤.     

Isoflurane Provides Long-term Protection against Focal Cerebral Ischemia in the Rat

Background: Long-term neuroprotection by isoflurane has been questioned. The authors examined factors in experimental models potentially critical to definition of enduring isoflurane neuroprotection.

Methods: Rats were prepared for temporary middle cerebral artery occlusion (MCAO). Pericranial normothermia was maintained. Neurologic deficits (range, 0-48; 0 = no deficit) and cerebral infarct volumes were measured. In experiment 1, rats underwent 50 or 80 min MCAO while awake or anesthetized with 1.8% isoflurane. Blood pressure was controlled with phenylephrine. Outcome was evaluated 2 weeks later. In experiment 2, rats underwent 50 min MCAO while awake or anesthetized with isoflurane, with outcome evaluated 8 weeks later. In experiment 3, rats underwent 50 min MCAO while awake or anesthetized with isoflurane and 2 weeks recovery. Effects of phenylephrine and the mitochondrial adenosine triphosphate-sensitive K+ channel antagonist 5-hydroxydecanoate were studied. In experiment 4, isoflurane-anesthetized rats underwent 50 min MCAO with permanent or temporary common carotid artery occlusion, with outcome evaluated 2 weeks later.

Results: In experiment 1, isoflurane reduced neurologic deficit (median +/- interquartile range; awake vs. isoflurane: 11 +/- 12 vs. 8 +/- 6 for 80 min and 13 +/- 4 vs. 3 +/- 9 for 50 min; P = 0.0006) and infarct size (160 +/- 97 vs. 84 +/- 62 mm3 for 80 min and 169 +/- 78 vs. 68 +/- 61 mm3 for 50 min; P < 0.0001). In experiment 2, isoflurane protection persisted at 8 weeks after ischemia. In experiment 3, there was no effect of phenylephrine or 5-hydroxydecanoate. In experiment 4, permanent common carotid ligation increased infarct size threefold versus temporary occlusion.     

异丙酚对大鼠局灶性脑缺血再灌注后Ca2+诱发神经元线粒体损伤的影响

目的 评价异丙酚对大鼠局灶性脑缺血再灌注后Ca2+诱发神经元线粒体损伤的影响.方法 健康雄性Wistar大鼠84只,体重250～300 g,随机分为4组(n=21),假手术组(S组)仅暴露颈内动脉但不结扎颈总动脉;缺血再灌注组(IR组)、CaCl2组和异丙酚组(P组)采用结扎颈总动脉的方法建立大鼠局灶性脑缺血再灌注模型,缺血2 h,再灌注24 h.缺血2 h时进行神经功能缺陷评分.再灌注24 h时处死大鼠,分离额叶皮质,提取神经元线粒体.CaCl2组加入CaCl2 200μmol/L于37 ℃下孵育5 min;P组加入异丙酚200 μmol/L于37℃下孵育2 min后,再加入CaCl2 200 μmol/L孵育5 min.透射电镜下观察线粒体超微结构.采用紫外分光光度法检测线粒体通透性转换孔(MPTP)的活性.结果 S组神经功能缺陷评分为0分,IR组、CaCl2组和P组神经功能缺陷评分为2～3分.CaCl2组线粒体明显肿胀,基质电子密度低,嵴大部分断裂,线粒体膜崩解;P组较CaCl2组病理学损伤减轻.与S组比较,IR组和CaCl2组MPTP活性升高,P组MPTP活性降低(P＜0.05);与IR组比较,CaCl2组MPTP活性升高,P组MPTP活性降低(P＜0.05);与CaCl2组比较,P组MPTP活性降低(P＜0.05).结论 异丙酚可减轻大鼠局灶性脑缺血再灌注后Ca2+诱发的神经元损伤,与其抑制MPTP的开放有关.     

Comparison of the effects of isoflurane and thiopental on neurologic outcome and neuropathology after temporary focal cerebral ischemia in primates

In an attempt to determine whether one anesthetic might be clearly advantageous over another in clinical situations of temporary focal ischemia, isoflurane or thiopental (in concentrations producing equal suppression of cerebral function as measured by the electroencephalogram) were studied for their effects on neurologic outcome and cerebral infarct size in pigtailed monkeys exposed to temporary focal ischemia produced by 5 h of middle cerebral artery occlusion (MCAo). Burst suppression was produced for 15 min before MCAo and maintained throughout the ischemic period by 2.18 +/- 0.11% (mean +/- SE) end-expired isoflurane or 135 +/- 18 mg.kg-1 thiopental. Mean arterial pressure was supported with phenylephrine and maintained at approximately 90 mmHg in both groups throughout the ischemic period. At the end of the ischemic period, the isoflurane or thiopental was discontinued, allowing the animals to awaken. Intensive care was provided as needed. Neurologic function was scored for 8 days at the end of which surviving animals were killed and the brains were fixed in formalin and then examined for infarct size. There was no significant difference in final neurologic outcome between the animals receiving isoflurane and those receiving thiopental as determined by the Mann-Whitney rank sum test. Neurologic deficit scores ranged from normal (one of eight in the group receiving isoflurane and three of nine in the group receiving thiopental) to death resulting from brain injury (three in the isoflurane group and five in the thiopental-treated group). There also was no significant difference in infarct size between the two groups.(ABSTRACT TRUNCATED AT 250 WORDS)     

Comparison of the Effects of Propofol and Pentobarbital on Neurologic Outcome and Cerebral Infarct Size after Temporary Focal Ischemia in the Rat

Background: Although propofol is known to have effects on cerebral physiology similar to the barbiturates, a direct comparison of the relative effects of these drugs on outcome from cerebral ischemia has not been performed. The authors postulated that pentobarbital or propofol would yield similar effects on neurologic and histologic outcome from temporary focal ischemia in the rat.

Methods: Wistar rats were anesthetized with sufficient doses of pentobarbital (n = 20) or propofol (n = 20) to cause electroencephalographic burst suppression. The middle cerebral artery was then occluded for 75 min. Animals were awakened 4-6 h after onset of reperfusion and allowed to recover for 1 week. Neurologic function and infarct size were then assessed.

Results: Relevant physiologic values were similar between groups during ischemia and early reperfusion. No difference between groups was observed for severity of hemiparesis (P = 0.10). Total cerebral infarct volumes (median +/- quartile deviation) were similar for the two groups (pentobarbital = 190 +/- 36 mm3; propofol = 200 +/- 24 mm3, P = 0.35).