Involvement of Apoptosis in 3-nitropropionic Acid-induced Ischemicl Tolerance to Transient Focal Cerebral Ischemia in Rats

Preconditioningofbraintissueswithsub lethalstressesorstimulicanresultinresistancetosubse quentlethalischemiceventsinaresponsecalledis chemictolerance .Recently ,severalstudieshaveshownthatasinglesystemicdoseof 2 0mg/kg 3 NPAcausednohistopathologicalabnorm…     

Regional cerebral blood flow after occlusion of the middle cerebral artery

Occlusions of the middle cerebral artery (MCA) are mostly of embolic origin (appr. 80%) and give rise to about one third of all ischemic strokes, most of these being major strokes. MCA occlusions lasting for less than 1/2 h are tolerated without occurrence of permanent tissue damage. Occlusions lasting between 1/2 h to 4-8 h lead to permanent tissue damage and neurological deficits that are proportional to the duration of occlusion. Maximal tissue damage is obtained after 4-8 h occlusion. A cerebral blood flow of 8-23 ml/100 gr/min is sufficient for cellular viability but insufficient for normal tissue function ("ischemic penumbra"). Cellular function is completely abolished in the interval 8-16 ml/100 gr/min and flow at that level is tolerated only for 1-3 h before neuronal death ensues. In the interval 18-23 ml/100 gr/min there is some functional activity although it is reduced. Experimental and clinical evidence suggests that flow in this interval may be tolerated for several days, months or even longer ("chronic ischemic penumbra"). After MCA occlusion the blood flow falls below 8 ml/100 gr/min in most cases and permanent MCA occlusion always leads to relatively large areas of frank infarction. The ischemic infarcts may be surrounded by collaterally perfused areas where the blood flow is pressure-dependent (impaired autoregulation) and quite commonly insufficient for normal neuronal function (below 23 ml/100 gr/min). Such collaterally perfused areas may include a "chronic ischemic penumbra". Emboli causing MCA occlusions commonly disintegrate and/or migrate more peripherally within the first few weeks post stroke. This leads to reperfusion and changes of ischemic infarcts into hyperemic infarcts where flow is severely increased. The vascular reactivity is completely abolished in hyperemic infarcts and the hyperemic state lasts for about two weeks. Probably, anemic infarcts are equivalent to ischemic infarcts while the hemorrhagic variety is equivalent to hyperemic infarcts. The "partial infarct" with selective neuronal necrosis occurs in experimental animals after MCA occlusions of less than four h but not after permanent MCA occlusion. The significance of partial infarction in human stroke is not clarified. The extent of irreversible tissue damage can be reduced only if therapy sets in within 4-8 h after the occlusion. If a "chronic penumbra" exists the extension of reversible tissue damage can be reduced if therapy aimed at increasing the blood flow in the penumbra sets in within weeks or even months after the stroke.(ABSTRACT TRUNCATED AT 400 WORDS)     

3-硝基丙酸预处理对大鼠局灶性脑缺血Caspase-3表达和活性的影响

目的探讨小剂量线粒体毒素3-硝基丙酸(3-nitropropionic acid,3-NPA)预处理对大鼠局灶性脑缺血半暗带半胱天冬酶-3(Caspase-3)表达和活性的影响。方法大鼠腹腔注射3-NPA20mg/kg或生理盐水3d后制作局灶性脑缺血再灌注模型,采用免疫印迹技术和荧光测定法观察3-NPA预处理对缺血2h再灌注24hCaspase-3的表达和活性的影响。结果缺血2h再灌注24h3-NPA预处理组Caspase-3表达减弱(P<0.05),活性降低(P<0.05),与对照组比较差异有显著性。结论3-NPA预处理诱导脑缺血耐受与降低Caspase-3活性,进而抑制神经细胞凋亡有关。     

磁共振扩散成像和波谱技术对超急性脑梗死缺血半暗带的界定

目的 应用磁共振扩散成像(DWI)和波谱(MRS)技术界定超急性脑梗死缺血半暗带,力求提出量化评定标准.方法 13例发病时间在2～6 h以内的超急性脑梗死患者行MRI检查,包括DWI及MRS技术,并在2～28 d内复查T2 WI确定最终梗死范围.对梗死中心区、缺血半暗带及对侧镜像区,测量其扩散变化及代谢改变.结果 ①梗死中心区与缺血半暗带表观扩散系数(ADC)平均值分别为7.01×10-4 mm2/s及9.36×10-4 mm2/s,相对ADC(rADC)平均值分别为0.63及0.87,梗死中心区ADC及rADC均明显降低,缺血半暗带ADC及rADC轻度下降,二者之间差异有显著性意义(P＜0.05).②超急性脑梗死的典型MRS改变为乳酸(Lac)浓度升高和氮-乙酰天门冬氨酸盐(NAA)水平降低.以肌酸和磷酸肌酸(Cr)为内标准的NAA/Cr比值、Lac/Cr比值及相对NAA(rNAA)在梗死中心区与缺血半暗带之间差异均无显著性意义(P＞0.05).③缺血半暗带区ADC值轻度降低(＜22%)、Lac升高且NAA正常或轻度下降(＜14%);而ADC值明显降低(25%～53%)、Lac升高且NAA明显下降(16%～34%)的区域为不可逆损伤区的可能性大.④1例疑腔隙性脑梗死发病2 h DWI见右丘脑小团异常高信号灶,ADC下降幅度为16%,11d后复查T2 WI见原右丘脑高信号完全消失,提示为缺血半暗带,而非梗死.结论 DWI和MRS的联合应用可发现超急性脑梗死,并预测缺血半暗带.     

The Effect of Dose Grid Resolution on Dose Volume Histograms for Slender Organs at Risk during Pelvic Intensity-modulated Radiotherapy

PurposeThere are enduring uncertainties regarding the optimal dose grid resolution for use with pelvic intensity-modulated radiotherapy (IMRT) plans in which the adjacent organs at risk are slender and transect the field edge. Therefore, this study evaluated the effect of dose grid resolution on bladder wall dose-volume histogram (DVH) calculations for prostate IMRT plans.Materials and MethodsThe planning computed tomography scans and clinical plans from 15 prostate cancer patients were included in this analysis. For each study computed tomography, the entire inner and outer bladder surfaces were delineated. Nine versions of the clinical plan were created, varying interval between the dose grid calculation points uniformly in three dimensions, whereas all other plan parameters were kept constant. The dose grid increments tested were 1–10 mm. The plans were recalculated and the bladder wall DVH compared against the study benchmark (1 mm grid).ResultsAll the dose grid increments evaluated resulted in a systematic overestimation of the bladder wall volume receiving low doses and an underestimation of the volume receiving high doses. Grid increments <2.5 mm all resulted in mean volume differences less than 1 cm³ across the whole DVH. Grid increments >5.0 mm resulted in mean volume differences greater than 2 cm³. Individual patient analysis revealed that only the 1.5 mm increment resulted in maximum volume differences ≤1 cm³ for every patient across the full length of the DVH curve. Bladder wall thickness ranged from 1.7 to 4.4 mm and displayed no correlation with the magnitude of the dose grid effect.ConclusionsFor an accurate DVH calculation for bladder wall during IMRT planning for prostate cancer, a 1.5 mm dose grid increment is recommended. This finding was unaffected by a normal range in bladder wall thickness. It is suggested that the application of any new treatment planning technique or organ delineation method be accompanied with an evaluation of optimal dose grid resolution.     

Evolution of the stroke paradigm: A review of delayed recanalization

While the time window for reperfusion after ischemic stroke continues to increase, many patients are not candidates for reperfusion under current guidelines that allow for reperfusion within 24 h after last known well time; however, many case studies report favorable outcomes beyond 24 h after symptom onset for both spontaneous and medically induced recanalization. Furthermore, modern imaging allows for identification of penumbra at extended time points, and reperfusion risk factors and complications are becoming better understood. Taken together, continued urgency exists to better understand the pathophysiologic mechanisms and ideal setting of delayed recanalization beyond 24 h after onset of ischemia.     

Penumbra around chronic cerebral infarction?

In a series of 13 patients with cerebrovascular occlusive disease regional cerebral blood flow (rCBF) measurements (two-dimensional intravenous ¹³³Xe clearance method) and quantitative EEG analysis (sensorimotor rhythms) as well as electronic measurement of handforce were performed before and during intravenous infusion of 1 μg kg/min of one of the lipophilic dihydropyridine calcium channel blocker nimodipine (Nimotop®). The aim of the study was to test the hypothesis of the existence of hypoperfusion (ischaemic penumbra) in the surroundings of chronic cerebral infarcts. All 3 parameters improved in one patient. Sensorimotor rhythms increased in 5 patients, rCBF in 3. EEG and rCBF improved in 2 patients. In 3 instances, a redistribution of rCBF in favour of the peri-infarct zone was noted (significant increase of rCBF from 35 ± 2 sem to 53 ± 4 ml/100 g/min (p > 0.01), whereas rCBF fell from 61 ± 5 to 46 ±2 ml/100 g/min on a collimator remote from the infarct but in the infarcted hemisphere. The parallel improvement of rCBF and EEG in brain regions surrounding chronic infarcts in 3 patients was interpreted as functional improvement as a consequence of nimodipine-induced normalization of peri-infarct hypoperfusion, i.e. reversal of flow-dependent neuronal silence and/or dysfunction.     

老龄大鼠局灶性脑缺血周围区DNA损伤的研究

目的　探讨老龄大鼠局灶性脑缺血周围DNA损伤特点。方法　应用HE染色、原位末端标记法 (TUNEL)标记、原位分子杂交、免疫组织化学等方法 ,分别对缺血 4、2 4h和 5d组大鼠脑组织中坏死细胞、凋亡细胞、p5 3mR NA、p5 3蛋白阳性细胞密度及空间分布进行观察和比较。结果　不同时间点病灶周围每高倍视野TUNEL、p5 3蛋白、p5 3mRNA的阳性细胞数分别为 4h :8.0± 1.5、2 5 .1± 2 .6、10 .3± 1.9;2 4h :2 0 .5± 2 .4、6 0 .0± 4.8、2 2 .0± 1.8;5d :2 .1± 0 .4、3.6± 1.4、3.5± 0 .8。p5 3基因主要在形态完整和可逆性损伤细胞中表达、分布范围较TUNEL细胞广泛。结论　局灶性脑缺血后 ,缺血周围DNA损伤区大于凋亡区 ,p5 3基因表达范围可能代表病理意义上的半暗带 ;p5 3主要发挥DNA修复作用