亚低温对完全性脑缺血再灌注后丙二醛含量和超氧化物歧化酶活性的影响

目的：观察完全性脑缺血再灌注后全脑亚低温对脑组织丙二醛（ＭＤＡ）含量和超氧化物歧化酶（ＳＯＤ）活性的影响．方法：将１７只犬随机分为三组：非缺血对照组、缺血对照组和亚低温治疗组，采用谭秀娟等建立的心脏停跳复苏动物模型，于心肺复苏后４小时取脑组织测定ＭＤＡ含量和ＳＯＤ活性．结果：全脑缺血１０分钟后再灌流４小时，脑组织ＭＤＡ含量明显上升（Ｐ＜０．０１），ＳＯＤ活性下降（Ｐ＜０．０１）；而３４℃亚低温治疗组与缺血对照组比较，ＭＤＡ含量明显下降（Ｐ＜０．０１），ＳＯＤ活性上升（Ｐ＜０．０１）．结论：完全性脑缺血再灌注后全脑亚低温可抑制脑内脂质过氧化反应，保护脑组织自身抗氧化能力，有利于脑复苏．     

亚低温对实验犬复苏后血清及脑脊液中血小板活化因子含量的影响

目的 探讨亚低温治疗的脑保护作用机制。方法 采用犬室颤致心跳骤停动物模型,观察复苏过程中亚低温治疗对血清及脑脊液中血小板活化因子（ＰＡＦ）含量的影响。结果 ①复苏后血清及脑脊液中ＰＡＦ含量较心跳骤停前明显升高（Ｐ〈０．０１）;②亚低温治疗组脑脊液中ＰＡＦ含量明显低于常温对照组（Ｐ〈０．０１）,而血清中ＰＡＦ含量两组间无明显差异。结论 ＰＡＦ在缺血及再灌注脑损害中起重要作用,亚低温抑制复苏后脑组织中     

亚低温对脑缺血再灌注损伤后神经功能的保护作用及机制研究

目的：验证亚低温对脑缺血后神经功能的保护作用．方法：将４６只ＳＤ大鼠随机分为对照组、缺血组和亚低温治疗组（肛温维持在３２～３３℃之间），分别在急性和慢性条件下进行．参照Ｐｕｌｓｉｎｅｌｉ和Ｂｒｉｅｒｌｅｙ的方法建立脑缺血动物模型，并观察神经行为学、病理学及Ｎａ＋－Ｋ＋－ＡＴＰ酶活性与脑组织含水量的改变．结果：与对照组和缺血组相比，亚低温能显著缓解Ｎａ＋－Ｋ＋－ＡＴＰ酶活性的降低（Ｐ＜０．０１），改善神经行为学异常并降低脑组织含水量（Ｐ＜０．０５）．结论：亚低温能明显减轻缺血后脑组织病理形态学的损害程度，对神经功能的恢复起促进作用．其机制与恢复能量供给，保护血脑屏障，减轻脑水肿等有关．     

AKT信号通路通过亚低温对大鼠局脑缺血再灌注损伤神经元的保护作用

目的通过检测AKT及Bcl-2蛋白的表达,探讨亚低温对局脑缺血再灌注后神经元存活的影响。方法用线拴法制作大鼠大脑中动脉闭塞（MCAO）局脑缺血再灌注模型,将36只SD大鼠随机分成假手术组、常温缺血再灌注组和亚低温缺血再灌注组,缺血组分别缺血6h再灌注4h、24h、72h、1w（n=4）后处死,亚低温组于缺血后13~14min实施病灶侧亚低温持续4h。免疫组织化学法检测AKT、Bcl-2蛋白的表达,电镜检测自噬小体。结果不同缺血时间再灌注4h,亚低温组比常温组缺血侧半暗带AKT表达水平显著增高（P〈0.05）,Bcl-2表达明显降低（P〈0.01）;亚低温组自噬小体明显减少。结论病灶侧亚低温通过促进缺血半暗带脑组织AKT表达,抑制Bcl-2表达,从而抑制神经元凋亡,抑制自噬的产生,从而对神经元起保护作用,促进脑缺血后神经功能恢复。     

亚低温治疗对重型脑创伤脑组织糖代谢及甘油的影响

目的研究亚低温对重型脑创伤患者脑组织糖代谢及甘油的影响. 方法 33例患者随机分为亚低温组和常温组,将微透析探针分别置入病损周边区、病灶对侧的相应位置及腹部皮下脂肪组织,分析亚低温组及常温组脑细胞间液(extracellular fluid, ECF)的乳酸/丙酮酸 (lactate/pyruvate,L/P)、乳酸/葡萄糖(lactate/glucose,L/G)及甘油(glycerol,Gly)浓度. 结果亚低温组比常温组““““正常区““““脑 ECF的L/P有明显降低;亚低温组比常温组病损周边区甘油、L/G及L/P有明显降低;常温组病损周边区比““““正常区““““的甘油、L/G及L/P明显增高;亚低温组病损周边区L/P比““““正常区““““ 有明显增高. 结论亚低温治疗可能通过降低病损周边区脑ECF中L/P、L/G及甘油的浓度及““““正常区““““ L/P的浓度而发挥脑保护作用;颅脑创伤后病损周边区更易发生能量代谢紊乱及细胞膜降解,亚低温对这一区域有显著保护作用.     

业低温对脑缺血再灌注损伤后神经功能的保护作用及机制研究

目的；验证亚低温对脑缺血后神经功能的保护作用。方法；将４６只ＳＤ大鼠随机分为对照组，缺血组和亚低温治疗组，分别在生和慢性条件下进行。参照Ｐｕｌｓｉｎｅｌｌｌｉ和Ｂｒｉｅｒｌｅｙ的方法建立脑缺血动物模型，并观察神经行为学、１病理学及ＮａＫ－ＡＴＰ酶活性与脑组织含水量的改变。结果；与对照组和缺血级箱比，业低温能显著缓解Ｎａａ－Ｋ－ＡＴＰ酶活性的降低（Ｐ〈０．０１），改善神经行为学异常并降低脑组织含水量     

亚低温治疗对脑创伤后三磷酸腺苷酶的影响

目的 观察亚低温治疗对大鼠脑外伤后脑组织Na^ -K^ -ATP酶、Mg^2 -ATP酶以及Ca^ -ATP酶的影响。方法 75只大鼠随机分为常温对照组（33只）、常温受伤组（22只）和亚低温治疗组（20只）,后两组用自由落体方法致大鼠左侧脑外伤,亚低温治疗组受伤后用冰袋全身降温至脑温30℃后维持1h,然后加热复温至37℃。每组大鼠在伤后3h,1,3,5和7d取大脑组织,测定组织匀浆液中ATP酶的活性。结果 （1）Na^ -K^ -ATP酶;常温受伤组和亚低温治疗组在3h明显高于对照组,而后明显下降。亚代温治疗组在第3天明显高于常温受伤组;（2)Mg^2 -ATP酶;常温受伤组和亚低温治疗组在1d后才开始明显下降,但亚低温治疗组在1d和3d中较常温组睛降速度明显变慢;（3）Ca^2 -ATP酶：常温受伤组第1天就较常温对照组明显下降,而亚低温治疗组3h和第1天保持正常,有3天才明显下降,但仍然显著高于常温受伤组。结论（1）脑外伤大鼠脑细胞Na^2 -K^ -ATP酶早期对脑外伤有应激反应,亚低温治疗对细胞钠通道的作用不明显;（2）亚低温对钙泵有明显的调节作用,较常温受伤组显著提高脑细胞Ca^2 -Mg^2 -ATP酶的活性;（3）亚低温治疗能延缓脑细胞钙通道的损伤时间,且在7d内脑细胞的钠通道和钙通道在低水平保持相对稳定,从而减少Ca^2 的内流,减轻脑水肿。     

亚低温治疗重型颅脑损伤的临床应用及脑氧代谢研究

目的　探讨亚低温疗法对重型颅脑损伤患者的脑保护机理及临床疗效。方法　 112例重型颅脑损伤患者 (GCS≤ 8分 )随机分为亚低温治疗组和常温治疗组。亚低温组 6 5例 ,于伤后 4～ 12小时内行亚低温治疗 ,术中将脑温探头置于硬膜下腔 ,将脑温控制在 32～ 35℃。亚低温治疗 4～ 7天 ,同时检测颈动脉和颈静脉血气及电解质变化、颅内压 (ICP)、血糖及生命体征等指标。常温组除未行亚低温治疗外 ,其余治疗及监测方法同亚低温组。两组病人均于伤后 3个月根据GOS预后评分判定疗效。结果　与常温组比较 ,亚低温治疗组病人脑氧耗明显好转 ,伤后早期高颅压 (ICP)、高血糖情况分别显著下降 ,生命体征及电解质等无明显差异 ,无严重并发症 ,死残率明显降低 ,预后显著改善。结论　亚低温具有显著的脑保护作用 ,临床应用于重型颅脑损伤的救治安全有效 ,无严重并发症     

脑创伤大鼠透析液一氧化氮变化及亚低温治疗的影响

目的　研究脑创伤大鼠致伤后致伤中心、致伤区外侧侧脑室和致伤对侧海马区透析液一氧化氮 (NO)的变化以及亚低温治疗的影响。　方法　选用Wistar大鼠制作大鼠脑创伤模型 ;随机分为正常对照组、常温致伤组和亚低温治疗组 ;透析管插入致伤区中心、致伤区外侧侧脑室和致伤对侧海马区 ,灌流速度为 4 μl min ,透析 5h。亚低温治疗组在脑创伤后用冰袋全身降温至脑温30℃保持 1h ,然后加热复温至 37℃。　结果　 (1)正常对照组致伤区中心、致伤区外侧侧脑室和致伤对侧海马区的NO分别为 (14 .17± 2 .0 3)、(2 5 .4 3± 1.2 7)、(17.10± 1.83) μmol L ;(2 )致伤区中心NO :常温致伤组明显升高 (P <0 .0 5 ) ,伤后 0 .5h最高 ;亚低温治疗组伤后 1hNO较正常对照组明显升高 ,0 .5h明显低于常温致伤组 ;(3)致伤区外侧NO :常温致伤组伤后与正常对照组无区别 ;亚低温治疗组NO较两组明显降低 ,复温后逐渐恢复 ,但仍明显比常温致伤组低 ;(4)对侧海马区NO :常温致伤组和亚低温治疗组NO均下降 ,但两组之间差异无显著性意义。　结论　亚低温治疗对脑创伤后早期致伤区中心组织NO有一定的抑制作用 ,对致伤对侧海马区NO无影响 ,主要是明显降低了致伤区外侧正常脑组织细胞外液NO的水平 ,具有保护脑创伤后正常组织的作用 ,从而     

重型脑伤患者亚低温治疗后脑组织氧分压、二氧化碳分压和pH值的变化

目的 探讨重型颅脑损作患者亚低温（33－35℃）治疗后的脑组织氧分压（PtiO2）、二氧化碳分压（PtiCO2）和pH值的变化及其临床意义。方法 重型脑伤患者（GCS3－8分）41例，随机分为亚低温治疗组21例，常温对照组20例。动态监测伤后急性期脑组织PtiO2、PtiCO2和pH值，观察两组各个指标的变化及其与预后的关系。结果 亚低温治疗24h后，服组织PtiO2和pH值逐渐上升，PtiO2逐渐下降，并趋于正常，与对照组比较，差异有显著性意义（P＜0．05）。持续性PtiO2＜1．33kPa的患者死亡率明显高于PtiO2≥1．33kPa的患者（P＜0．05）。结论 亚低温治疗能减轻脑伤患者的服组织氧代谢紊乱，改善预后，且需尽早进行。脑组织PtiO2、PtiCO2和pH值动态监测技术安全可靠，对临床判断病情、指导治疗具有重要意义。     

PET measurement of FK506 concentration in a monkey model of stroke

INTRODUCTION: The immunosuppressive agent FK506 (tacrolimus) has neuroprotective properties in an experimental model of cerebral ischemia. To improve the accuracy of clinical studies in acute stroke, a clinical dose setting should be based on the brain concentration, but not on the blood concentration of agents in humans. We have already established a measurement method using PET for FK506 concentration in the normal monkey brain, which could be applicable for human study; however, under ischemic conditions, in this study, we aimed to examine the brain concentration of FK506 in a monkey model of stroke. METHODS: Studies were performed on six male cynomolgus monkeys (Macaca fascicularis) and a middle cerebral artery (MCA) occlusion model was used. Regional cerebral blood flow (rCBF) was measured by an intravenous injection of [(15)O]H(2)O 165 min after MCA occlusion. FK506 (0.1 mg/kg) containing [(11)C]FK506 was intravenously injected into the monkeys 180 min after MCA occlusion, and dynamic PET images were acquired for 30 min after administration. FK506 concentrations in the brain were calculated in moles per liter (M) units using the specific activity of injected FK506. RESULTS: MCA occlusion produced ischemia, confirmed by rCBF measurement before the administration of [(11)C]FK506. Fifteen minutes after FK506 (0.1 mg/kg) administration, the concentrations in the contralateral and ipsilateral cortex were 22.4+/-6.4 and 19.7+/-4.0 ng/g, respectively. CONCLUSION: We successfully measured the brain concentration of FK506 in a monkey model of stroke. The difference between the contralateral and ipsilateral concentrations of FK506 was not significant. This characteristic that FK506 readily penetrates ischemic tissue as well as normal tissue might explain the neuroprotective effect of FK506 in the ischemic brain and is suitable for the treatment of stroke patients.     

Neuroprotective effects of an immunosuppressant agent on diffusion/perfusion mismatch in transient focal ischemia.

The immunosuppressant FK506 (tacrolimus) exerts potent neuroprotection following focal ischemia in animals; however, the separate effects of FK506 on the ischemic core and penumbra have not been reported. The ischemic penumbra is clinically defined as the difference between a large abnormal area on perfusion-weighted imaging (PWI) and a smaller lesion on diffusion-weighted imaging (DWI). The goal of this study was to determine the effect of FK506 on DWI/PWI match and mismatch areas in transient focal ischemia in rats. Twelve rats were subjected to 1 hr of transient middle cerebral artery (MCA) occlusion, and given an intravenous injection of a placebo (N = 6) or 1 mg/kg FK506 (N = 6) immediately before reperfusion. Magnetic resonance imaging (MRI) was performed during MCA occlusion, and 0.5, 1, and 24 hr after reperfusion. FK506 significantly protected the ischemic brain only in the mismatch cortex where the initial apparent diffusion coefficient (ADC) was normal and there was a mild reduction of cerebral blood flow (CBF). This is the first report to describe the protective effects of FK506 on ischemic penumbra, as measured by DWI/PWI mismatch. The findings provide direct evidence for the utility of DWI/PWI mismatch as a guideline for therapeutic intervention with FK506.     

FK506 attenuates early ischemic neuronal death in a monkey model of stroke.

FK506 is an immunosuppressive agent that has been reported to have neuroprotective effects in several kinds of rodent models of stroke. The purpose of this study was to evaluate the neuroprotective effects of FK506 in a monkey model of stroke. METHODS: Cynomolgus monkeys underwent 3 h of occlusion followed by 5 h of reperfusion of the right middle cerebral artery (MCA) through a transorbital approach. A single bolus dose of FK506 (0.1 mg/kg) was injected intravenously 5 or 175 min after MCA occlusion. Eight hours after ischemia, a neuropathologic study was performed and the volume of ischemic damage was determined. To measure local cerebral blood flow (CBF), the cerebral metabolic rate of oxygen (CMRO(2)), and the oxygen extraction fraction during the experiments, PET scans were obtained using a steady-state (15)O continuous-inhalation method. Four consecutive PET scans (before and 2 h after ischemia and immediately and 3 h after reperfusion) were obtained on each monkey. RESULTS: Treatment with FK506 (0.1 mg/kg) 5 or 175 min after ischemia significantly reduced cortical damage 8 h after ischemia by 82% (P < 0.05) and 73% (P < 0.05), respectively. In PET studies, FK506 did not affect CBF or physiologic parameters in any treatments. In the FK506-treated group, a volume of >40% CMRO(2) reduction 3 h after reperfusion decreased significantly (P < 0.05). CONCLUSION: This study showed that FK506 showed a powerful neuroprotective effect in a nonhuman primate model of stroke. The therapeutic time window of FK506 was at least 3 h after onset. PET studies detected neuroprotective effects only in areas with >40% CMRO(2) reduction 3 h after reperfusion.     

Hyperglycemia augments ischemic brain injury: in vivo MR imaging/spectroscopic study with nicardipine in cats with occluded middle cerebral arteries

Hyperglycemia is often associated with an increased frequency of cerebrovascular disease and exacerbation of neuronal injury in focal ischemic cerebral infarction. We used a combination of high-field proton MR imaging and 1H and 31P MR spectroscopy to investigate whether hyperglycemia would adversely influence cerebral metabolism and eventual infarct size following unilateral occlusion of the middle cerebral artery (MCA) of cats pretreated with the calcium channel blocker nicardipine. Normoglycemic animals injected with 10 micrograms/kg of nicardipine (8 micrograms.kg-1.hr-1 maintenance dose) manifested only mild disturbances in phosphorus metabolism and cerebral pH regulation compared with untreated controls, and showed a significant reduction in infarct size 7 hr after MCA occlusion. By comparison, hyperglycemic cats (plasma glucose, 200-300 mg/dl) had significantly reduced cerebral high-energy phosphates, elevated lactic acid, and larger ischemic lesions in the occluded MCA territory, irrespective of whether they were treated with nicardipine. These results indicate that moderate hyperglycemia can exaggerate ischemic brain damage by enhancing formation of tissue lactic acid and impairing normal phosphorus metabolism. One implication of this study is that dextrose should not be provided to patients with acute ischemic stroke.     

局部亚低温对脑出血患者临床疗效及脑水肿的影响

目的 :研究观察应用局部亚低温治疗重症脑出血患者临床疗效及对脑水肿的影响。方法 :随机将 74例脑出血患者分为治疗组 36例和对照组 38例 ,治疗组在药物综合治疗基础上加用局部亚低温治疗 ,对照组为单纯药物综合治疗 ,治疗开始前及治疗后 2 1天分别进行神经功能缺损评分和脑血肿、脑水肿体积对比观察。结果 :治疗 2 1天后 ,治疗组的神经功能评分明显低于对照组 (P <0 .0 5 ) ;治疗组脑水肿体积较对照组明显减少 ,两组有显著差异 (P <0 .0 1) ;两组血肿体积无显著性差异 (P >0 .0 5 )。结论 :局部亚低温可促进脑出血患者的神经功能恢复、明显改善预后及减轻脑水肿作用。     

Relationship between vascular enhancement, cerebral hemodynamics, and MR angiography in cases of acute stroke

BACKGROUND AND PURPOSE: The use of MR angiography and contrast-enhanced T1-weighted MR imaging in cases of acute cerebral ischemia may be helpful in the evaluation of middle cerebral artery (MCA) occlusion and leptomeningeal collaterals, respectively. The aim of our work was to investigate the relationship between MCA occlusion, T1-weighted vascular contrast enhancement, hemodynamic alterations, and tissue damage in cases of acute ischemic stroke. METHODS: We studied the MCA territory in 15 patients with acute ischemic stroke within 8 hr of symptom onset. The first MR imaging study (<8 hr after onset) comprised diffusion-weighted imaging, MR angiography, perfusion-weighted imaging, and contrast-enhanced T1-weighted MR imaging sequences. Follow-up MR imaging, performed 1 week later, consisted of MR angiography and T2-weighted fluid-attenuated inversion recovery MR imaging. RESULTS: Early MR angiography showed MCA stem occlusion in nine of 15 patients. Patients with MCA occlusion had significantly larger areas of abnormality on early diffusion-weighted images, significantly larger areas of altered hemodynamics, larger final lesion volumes, and poorer clinical outcome. Among the nine patients with MCA stem occlusion, vascular enhancement was marked in seven and absent in two who had complete MCA infarcts and poor clinical outcome. Among patients with MCA patency, vascular enhancement was marked in only one, mild in four, and absent in one. Patients with marked vascular enhancement had significantly larger regions of altered hemodynamics and significantly higher asymmetries in both regional cerebral blood volume and mean transit time because of increased values in the affected hemisphere. CONCLUSION: Among patients with stroke with MCA occlusion, marked vascular enhancement and increased blood volume indicate efficient leptomeningeal collaterals and compensatory hemodynamic mechanisms.     

亚低温对颅脑损伤后脑血管内皮细胞紧密连接开放的影响

目的　观察颅脑损伤后早期亚低温治疗对脑毛细血管内皮细胞紧密连接开放的影响 ,阐明亚低温降低伤后血脑屏障通透性的可能机制。　方法　Wistar大鼠 90只 ,随机分为常温对照组 (10只 )、常温损伤组 (40只 )和亚低温治疗组 (40只 )。在镧示踪法电镜下分别观察亚低温及常温条件下颅脑损伤后内皮细胞紧密连接的开放及其程度 ;用干 -湿重法测定常温损伤组及亚低温治疗组伤后不同时相脑组织含水量并行统计学分析。　结果　常温损伤组伤后 3h紧密连接初步开放 ,2 4～ 4 8h紧密连接开放达高峰 ,72h紧密连接仍大量开放。亚低温治疗组紧密连接仅轻度开放 ;亚低温治疗组脑组织含水量较常温损伤组明显减少 ,伤后 3,2 4 ,72h差异有显著性意义(P <0 .0 5 ) ,伤后 4 8h差异有非常显著性意义 (P <0 .0 1)。　结论　亚低温有减轻颅脑损伤后血脑屏障毛细血管内皮细胞紧密连接的开放程度及减轻脑水肿的作用 ,亚低温减轻伤后内皮细胞紧密连接开放是降低伤后血脑屏障通透性机制之一。     

Correlation of angiographic and sequential CT findings in patients with evolving cerebral infarction

The usefulness of CT and angiography for predicting the final ischemic brain damage resulting from supratentorial ischemic stroke was evaluated in 36 patients. CT was performed within 4 hr and angiography within 6 hr after the onset of symptoms. CT was used to assess the site and size of parenchymal brain damage and angiography was used to evaluate the cerebral circulation. A 3-month follow-up CT study was used to determine the site and size of final ischemic damage. Angiography was normal in six patients and showed complete occlusion in 30. Angiographic findings in patients with arterial occlusion were classified as either internal carotid artery occlusion or middle cerebral artery (MCA) occlusion. MCA occlusions were subdivided into occlusion before the origin of internal lenticulostriate arteries (type 1), occlusion beyond the origin of these branches (type 2), occlusion at the bifurcation of the main trunk (type 3), and occlusion of the peripheral branches (type 4). Collateral blood supply was also studied. Early CT findings were positive in 25 of 36 patients; the lentiform nucleus alone, the lentiform nucleus and the cortex, or only the cortex were involved. In all patients with positive early CT findings, angiography showed an arterial occlusion, often located in the main trunk of the MCA. Involvement of the lentiform nucleus on early CT was always seen in patients with internal carotid artery or type 1 MCA occlusion.(ABSTRACT TRUNCATED AT 250 WORDS)     

Diffusion/perfusion MR imaging of acute cerebral ischemia

In vivo echo-planar MR imaging was used to measure apparent diffusion coefficients (ADC) of cerebral tissues in a comprehensive noninvasive evaluation of early ischemic brain damage induced by occlusion of the middle cerebral artery (MCA) in a cat model of acute regional stroke. Within 10 min after arterial occlusion, ADC was significantly lower in tissues within the vascular territory of the occluded MCA than in normally perfused tissues in the contralateral hemisphere. Sequential echo-planar imaging was then used in conjunction with bolus injections of the magnetic susceptibility contrast agent, dysprosium DTPA-BMA, to characterize the underlying cerebrovascular perfusion deficits. Normally perfused regions of brain were identified by a dose-dependent 35-70% loss of signal intensity within 6-8 s of contrast administration, whereas ischemic regions appeared relatively hyperintense. These data indicate that sequential diffusion/perfusion imaging may be useful in differentiating permanently damaged from reversibly ischemic brain tissue.