Acute cerebral infarction: pathophysiology and modern treatment concepts

Summary This review focuses on the pathophysiological changes in acute cerebral ischemia, with special emphasis on disturbances of the cerebral blood flow (CBF) and the associated penumbra concept. Alternatively, the model of peri-infarct depolarization is demonstrated. Metabolic and molecular changes caused by cerebral ischemia and reperfusion are discussed, namely energy failure, release of glutamate with an excitatoric burst, calcium influx in neurons, generation of free radicals, activation of different proteases, disturbances of protein synthesis, induction of gene expression and apoptosis, loss of membrane integrity, edema formation and microvascular disturbances. In summary, the pathophysiological changes after focal cerebral ischemia and reperfusion are most adequately described by a network of interacting different mechanisms of tissue alterations. The simple concept of a cascade of ischemic effects which would be easy to block seems to be less applicable. A time window of approximately 6 h for the acute stroke therapy is postulated on the base of the above mentioned pathophysiological changes. The recently introduced treatment regimen with optimized basic treatment, recanalization using thrombolysis and neuroprotection by different agents is presented. Different modes of a possible intervention are discussed. Modern concepts of stroke therapy including stroke-unit care and thrombolysis with add-on neuroprotection seem to have potential for improving the outcome of acute stroke patients.      

电针心经对心肌缺血性家兔心力环面积的影响

以心力环面积为指标，静脉滴注垂体后叶素造成家兔心肌缺血动物模型，结果表明，电针心经地心脏功能的调节作用比电针肺经显著，有相对特异性，说明心经作为一条经脉，与心脏机能活动有密切关系。     

Early Stroke Recognition: Developing an Out-of-hospital NIH Stroke Scale

Objective : To develop an abbreviated and practical neurologic scale that could assist emergency medical services or triage personnel in identifying patients with stroke.
Methods : A prospective, observational, cohort study was performed at university-based EDs. Participants were 74 patients treated in a thrombolytic stroke trial and 225 consecutive non-stroke patients evaluated during 4 random 12-hour shifts in the ED. Scores on the NIH Stroke Scale were obtained for all patients by physicians. Items of this scale were modified and recoded to a binomial (normal or abnormal) scale. Serial univariate analyses using χ² were performed to rank items. Recursive partitioning was then performed to develop the decision rule for predicting the presence of stroke.
Results : Three items identified 100% of patients with stroke: facial palsy, motor arm, and dysarthria. An Abbreviated NIH Stroke Scale based on these items had a sensitivity of 100% and a specificity of 92%. A proposed Out-of-hospital NIH Stroke Scale consisting of facial palsy, motor arm, and a combination of dysarthria and best language items (abnormal speech) had a sensitivity of 100% and a specificity of 88%.
Conclusion : Using the derivation data set, a proposed Out-of-hospital NIH Stroke Scale had a high sensitivity and specificity for identifying patients with stroke when performed by physicians in this group of 299 ED patients. Prospective studies of other health care professionals using the scale in the out-of-hospital arena are needed.     

不同脑缺血和再灌流过程中大鼠脑组织NO含量的动态变化

采用线栓法制成大鼠大脑中动脉梗塞 ( MCAO)模型 ,依 Hb O2 - NO法测定持续性脑缺血和缺血 /再灌流脑组织内 NO含量的变化 ,以探讨不同脑缺血和再灌流过程中 NO的变化规律及其意义。结果 :缺血 3小时受损脑组织 NO水平即增高 ,再灌流后 NO逐步升高 ,而持续性缺血状态下 NO则表现降低后再升高的变化。虽然两组 NO在 7天时均有明显降低 ,但仍高于缺血前水平。认为持续性脑缺血和缺血 /再灌流情况下 NO的变化规律有所不同 ,与缺血脑组织的缺氧及产生 NO所需底物供应缺乏有关 ,且可能与脑组织的损害密切相关     

Protein kinase C in focal ischemic rat brain: dual autoradiographic analysis of [C]iodoantipyrine (IAP) and [H]phorbol-12,13-dibutyrate (PDBu)

Protein kinase C (PKC) activity was measured in rat brain with 2 h of middle cerebral artery (MCA) and common carotid artery (CCA) occlusion, using dual autoradiography of [¹⁴C]iodoantipyrine (IAP) and [³H]phorbol-12,13-dibutyrate (PDBu). In the ischemic brain, it required more than 120 min of incubation to obtain a plateau in PDBu binding. In contrast, the binding of PDBu in non-ischemic brain reached a plateau with incubation for 60 min. This delay of PDBu binding in the ischemic brain suggests that the affinity of this ligand is reduced due to a change in structure of the cell membrane caused by ischemia. PDBu binding in the ischemic brain increased significantly compared to the non-ischemic brain. This finding provides further evidence that excessive activation of PKC in the ischemic brain may play an important role in ischemic neuronal damage. ©1997 Elsevier Science B.V. All rights reserved.     

Semipermeable Hollow Fiber Membranes in Hepatocyte Bioreactors: A Prerequisite for a Successful Bioartificial Liver?

Abstract: Recent studies have shown that liver support systems based on viable hepatocytes can prolong life in animal models of acute liver failure. Now the time has come to elucidate the design characteristics that are essential to construct an efficient bioreactor. The gold standard remains the intact liver. Despite the very high cell density in this organ, individual cell perfusion is guaranteed resulting in low diffusional gradients which are essential for optimal mass transfer. These conditions are not met in bioreactors based on hollow fiber membranes. Moreover, the semipermeable membranes can foul and act as a diffusional barrier between the hepatocytes and the blood or plasma of the recipient. We devised a novel bioreactor for use as a bioartificial liver that does not include hollow fiber membranes for blood or plasma perfusion. The device is based on an integral oxygenator and a nonwoven polyester matrix material for hepatocyte culture as small aggregates. The efficacy of this original design was tested in rats with liver ischemia. Preliminary results show statistically significantly improved survival; life was prolonged 100% compared to the control experiments.     

易卒中型肾血管性高血压大鼠的脑血流自动调节下限与最低耐受压

目的　研究易卒中型肾血管性高血压大鼠 (RHRSP)的脑血流 (CBF)自动调节下限及其最低耐受压。　　方法　用氢清除法测定RHRSP和正常SD大鼠在不同低血压水平时 ,一侧顶枕交界区皮质和海马的局部CBF(rCBF) ;72小时后计算RHRSP和SD大鼠海马CA1 区神经细胞 (CA1 NC)线粒体的体密度 (Vv)、比表面 (δ)、平均体积 ( V)和数密度 (Nv) ,　　 结果　正常SD大鼠在平均动脉压 (MABP)为 1 0 67kPa、9 3 3kPa和 8kPa时 ,rCBF值无显著减少。在MABP为 1 0 67kPa时 ,RHRSP的rCBF值显著减少 ;超微结构观察发现CA1 NC无明显缺血改变 ,当MABP为 9 3 3kPa时 ,CA1 NC缺血明显 ;细胞形态分析发现 9 3 3kPa组与 1 0 67kPa组比较 ,前者线粒体的Vv和 V显著增大 ,δ和Nv显著减小。　　结论　RHRSP的CBF自动调节下限上移至 1 0 67kPa,并与其最低耐受压十分接近 ,表明RHRSP是一种研究高血压脑血管损害较理想的动物模型     

电针对沙鼠急性脑缺血再灌注后神经原损伤的保护作用

本实验利用沙鼠急性脑缺血再灌注模型，研究电针对脑缺血及再灌注各期脑电活动的影响及组织病理学的改变。结果表明：缺血１０ｍｌｎ，脑电幅度受到严重抑制，甚至变平坦，总功率大大下降，再灌注后总功率难以恢复，在１２０ｍｉｎ时仅恢复到缺血前的２７．３９±１１．３１％，以后即不再进一步恢复，电针组动物缺血１０ｍｉｎ再灌注后，脑电的恢复明显比对照组快，１２０ｍｉｎ时恢复至缺血前的７１．４５±１６．４６％（Ｐ＜０．０１），２４０ｍｉｎ时继续恢复至缺血前的７５．２７±１８．４３％。同时电针能明显减轻缺血１０ｍｉｎ后再灌注２４小时的神经原缺血性损伤。结果提示：电针对急性脑缺血引起的神经原损伤具有保护作用，并能促进脑功能的恢复。     

Effect of temperature in focal ischemia of rat brain studied by 31P and 1H spectroscopic imaging

³¹P, ¹H and lactate spectroscopic imaging was used to evaluate the effects of hypothermia on focal cerebral ischemia produced by middle cerebral artery occlusion. The effects on high energy phosphate metabolism, pH, lactate and NAA were investigated in 24 spontaneously hypertensive rats subjected to either permanent or transient ischemia. Under either normothermic (37.5°C) or hypothermic (32°C) conditions, with permanent 6-h occlusion, there was little difference between groups in either the NMR measurements or the volume of infarction. In animals that underwent 3 h of ischemia followed by 12 h of reperfusion, the ischemic changes in lactate, pH, NAA, and high-energy phosphate returned toward control values, and there was a protective effect of hypothermia (infarct volume of 211 ± 26 and 40 ± 14 mm³ in normothermic and hypothermic groups, respectively). Thus, hypothermia did not ameliorate the changes in lactate, pH, NAA, or high energy phosphate levels occurring during ischemia, however, during reperfusion there was an improvement in both the recovery of these metabolites and pathological outcome in hypothermic compared with normothermic animals.