扩布性阻抑与脑缺血

研究表明,扩布性阻抑（ＳＤ）不仅与脑缺血,偏头痛,癫痫,颅脑创伤等疾患有关,而且可影响睡眠类型,觉醒等生理过程。本文重点对ＳＤ与脑缺血的关系进行了综述,订 叙述了以下几个问题：（１）ＳＤ的发现及研究简史;（２）完整脑内的ＳＤ;（３）局灶性脑梗塞周围的ＳＤ。     

Effect of myocardial infarction and ischemia on induction of cardiac reentries and ventricular fibrillation

The present work is aimed at investigating the effects of myocardial infarction and ischemia on induction of ventricular fibrillation. Electrophysiologic effects of global and local ischemia (variation of the dispersion of refractory periods as well as conduction velocity) on initiation of reentry mechanisms was studied by means of computer simulations based on a cellular automata model of propagation of activation wave through a ventricular surface element. A local area of ischemia where effects of the dispersion of refractory periods are investigated is then simulated. This is made using a Gaussian distribution characterized by its mean and standard deviation. These simulations show that ischemia is capable of initiating reentry phenomena which propagate through the whole ventricle; they are responsible for ventricular fibrillation which causes sudden cardiac death, even when ischemia only involves limited parts of the myocardium. Statistical study of the probability of reentries as a function of both of the size of ischemic zones and the rate of dispersion of refractory periods shows that the latter parameter is of primary importance in triggering cardiac reentries.     

Activation of c-Jun N-terminal kinase during ischemia and reperfusion in mouse liver

We have generated a mouse model for hepatic ischemia in which surgical subcutaneous transposition of the spleen allows hepatic ischemia to be applied without affecting other tissues. Using this mouse model we investigated the relationship between the length of ischemic periods in the liver and subsequent liver function; furthermore, we assayed the activation of c-Jun N-terminal kinase (JNK) during ischemia and reperfusion. Although prior to this study only the activated form of JNK was known to be translocated to the nucleus, we found that JNK translocates to the nucleus during ischemia without activation and is then activated during reperfusion. These results suggest a novel mechanism of JNK activation.     

脑缺血大鼠海马信号转导与转录激活子-3的激活及其调控

以往的研究表明,在脑缺血/再灌注的皮层和纹状体组织中信号转导与转录激活子-3(STAT3)被激活。本实验旨在研究SD大鼠四动脉结扎诱导的全脑缺血是否引起海马组织STAT3的快速激活及其调控机制。结果表明,脑缺血导致STAT3快速磷酸化激活及DNA结合活性增加。胞浆STAT3的磷酸化水平从缺血5min起就显著增高,10min达高峰(增加约1．7倍),然后开始下降。核内STAT3的磷酸化水平则逐渐增加,缺血30min时达高峰(增加约2．3倍)。电泳迁移率改变分析法显示,STAT3的DNA结合活性从缺血5min起就显著增加,30min达高峰(增加约3．2倍)。进一步的研究表明,缺血前20min腹腔注射给药,然后缺血30min,发现蛋白酪氨酸激酶抑制剂染料木黄酮和抗氧化剂N-乙酞半胱氨酸能显著地抑制核内STAT3的磷酸化水平及DNA结合活性的增加(磷酸化水平从2．3和2．5倍分别降为1．2和1．4倍,DNA结合活性则从2．8和3．7倍分别降为1．1和1．5倍),而蛋白酪氨酸磷酸酶抑制剂矾酸钠则能明显地促进他们的增高(磷酸化水平从2．0倍增到3．4倍,DNA结合活性从3．1倍增为5．1倍)。这些结果提示,蛋白酪氨酸激酶和蛋白酪氨酸磷酸酶可能共同参与了缺血诱导STAT3的激活调控,STAT3的激活可能有助于海马神经元适应氧化应激。     

Endothelin-1-induced spreading depression in rats is associated with a microarea of selective neuronal necrosis

Two different theories of migraine aura exist: In the vascular theory of Wolff, intracerebral vasoconstriction causes migraine aura via energy deficiency, whereas in the neuronal theory of Le?o and Morison, spreading depression (SD) initiates the aura. Recently, it has been shown that the cerebrovascular constrictor endothelin-1 (ET-1) elicits SD when applied to the cortical surface, a finding that could provide a bridge between the vascular and the neuronal theories of migraine aura. Several arguments support the notion that ET-1-induced SD results from local vasoconstriction, but definite proof is missing. If ET-1 induces SD via vasoconstriction/ischemia, then neuronal damage is likely to occur, contrasting with the fact that SD in the otherwise normal cortex is not associated with any lesion. To test this hypothesis, we have performed a comprehensive histologic study of the effects of ET-1 when applied topically to the cerebral cortex of halothane-anesthetized rats. Our assessment included histologic stainings and immunohistochemistry for glial fibrillary acidic protein, heat shock protein 70, and transferase dUTP nick-end labeling assay. During ET-1 application, we recorded (i) subarachnoid direct current (DC) electroencephalogram, (ii) local cerebral blood flow by laser-Doppler flowmetry, and (iii) changes of oxyhemoglobin and deoxyhemoglobin by spectroscopy. At an ET-1 concentration of 1 muM, at which only 6 of 12 animals generated SD, a microarea with selective neuronal death was found only in those animals demonstrating SD. In another five selected animals, which had not shown SD in response to ET-1, SD was triggered at a second cranial window by KCl and propagated from there to the window exposed to ET-1. This treatment also resulted in a microarea of neuronal damage. In contrast, SD invading from outside did not induce neuronal damage in the absence of ET-1 (n = 4) or in the presence of ET-1 if ET-1 was coapplied with BQ-123, an ET(A) receptor antagonist (n = 4). In conclusion, SD in presence of ET-1 induced a microarea of selective neuronal necrosis no matter where the SD originated. This effect of ET-1 appears to be mediated by the ET(A) receptor.     

Contributions of Ca2+ and Zn2+ to spreading depression-like events and neuronal injury

The phenomenon of spreading depression (SD) involves waves of profound neuronal and glial depolarization that spread throughout brain tissue. Under many conditions, tissue recovers full function after SD has occurred, but SD-like events are also associated with spread of injury following ischemia or trauma. Initial large cytosolic Ca²⁺ increases accompany all forms of SD, but persistently elevated Ca²⁺ loading is likely responsible for neuronal injury following SD in tissues where metabolic capacity is insufficient to restore ionic gradients. Ca²⁺ channels are also involved in the propagation of SD, but the channel subtypes and cation fluxes differ significantly when SD is triggered by different types of stimuli. Ca²⁺ influx via P/Q type channels is important for SD generated by localized application of high K⁺ solutions. In contrast, SD-like events recorded in in vitro ischemia models are not usually prevented by Ca²⁺ removal, but under some conditions, Zn²⁺ influx via L-type channels contributes to SD initiation. This review addresses different roles of Ca²⁺ in the initiation and consequences of SD, and discusses recent evidence that selective chelation of Zn²⁺ can be sufficient to prevent SD under circumstances that may have relevance for ischemic injury.     

基于单个细胞动作电位计算心电:若干异常仿真心电图

根据构造的心脏电生理模型及提出的基于单细胞动作电位计算心电图的算法,介绍异常心电活动的描述方式及对若干异常心电图的仿真结果,包括心肌缺血、心肌梗死、房室传导阻滞、束支传导阻滞、以及房室旁路,并对这些心电图的 产生机制进行说明,算法及仿真结果表明,细胞间的跨缝隙连结电位差是产生场点电热进而产生各种心电图波形的原因。     

Targeted tissue oxidation in the cerebral cortex induces local prolonged depolarization and cortical spreading depression in the rat brain

Spreading depression (SD) has been linked to several neurological disorders as epilepsy, migraine aura, trauma, and cerebral ischemia, which were also influenced by disorderliness of the brain redox homeostasis. To investigate whether local tissue oxidation directly induces SD, we oxidized a restricted local area of the rat cerebral cortex using photo-dynamic tissue oxidation (PDTO) technique and examined the cerebral blood flow (CBF) and direct current (DC) potential in and around the oxidized area. Intensive PDTO induced prolonged depolarization only in the photo-oxidized area, which led to global changes of CBF and DC potential: synchronous negative shifts of DC potential (with an amplitude of approximately 20 mV) and hyperperfusion of CBF occurred. The changes in DC potential and CBF spread at a rate of around 3mm/min beyond the oxidized area to the whole hemisphere of the cerebral cortex, indicating that intensive local oxidation induces SD in the rat brain.     

The Rate-Size Trade-Off Structures Intraspecific Variation in Daphnia ambigua Life History Parameters

The identification of trade-offs is necessary for understanding the evolution and maintenance of diversity. Here we employ the supply-demand (SD) body size optimization model to predict a trade-off between asymptotic body size and growth rate. We use the SD model to quantitatively predict the slope of the relationship between asymptotic body size and growth rate under high and low food regimes and then test the predictions against observations for Daphnia ambigua. Close quantitative agreement between observed and predicted slopes at both food levels lends support to the model and confirms that a ‘rate-size’ trade-off structures life history variation in this population. In contrast to classic life history expectations, growth and reproduction were positively correlated after controlling for the rate-size trade-off. We included 12 Daphnia clones in our study, but clone identity explained only some of the variation in life history traits. We also tested the hypothesis that growth rate would be positively related to intergenic spacer length (i.e. the growth rate hypothesis) across clones, but we found that clones with intermediate intergenic spacer lengths had larger asymptotic sizes and slower growth rates. Our results strongly support a resource-based optimization of body size following the SD model. Furthermore, because some resource allocation decisions necessarily precede others, understanding interdependent life history traits may require a more nested approach.     

A combined steepest descent and genetic algorithm (SD/GA) approach for the optimization of solvation parameters

An accurate solvation model is essential for computer modeling of protein folding and other biomolecular self-assembly processes. Compared to explicit solvent models, implicit solvent models, such as the Poisson-Boltzmann (PB) with solvent accessible surface area model (PB/SA), offer a much faster speed—the most compelling reason for the popularity of these implicit solvent models. Since these implicit solvent models typically use empirical parameters, such as atomic radii and the surface tensions, an optimal fit of these parameters is crucial for the final accuracy of properties such as solvation free energy and folding free energy. In this paper, we proposed a combined approach, namely SD/GA, which takes the advantage of both local optimization with the steepest descent (SD), and global optimization with the genetic algorithm (GA), for parameters optimization in multi-dimensional space. The SD/GA method is then applied to the optimization of solvation parameters in the non-polar cavity term of the PB/SA model. The results show that the newly optimized parameters from SD/GA not only increase the accuracy in the solvation free energies for ～200 organic molecules, but also significantly improve the free energy landscape of a β-hairpin folding. The current SD/GA method can be readily applied to other multi-dimensional parameter space optimization as well.     

The asymptotic behavior of solutions of the buffered bistable system

In this paper, we study a model for calcium buffering with bistable nonlinearity. We present some results on the stability of equilibrium states and show that there exists a threshold phenomenon in our model. In comparing with the model without buffers, we see that stationary buffers cannot destroy the asymptotic stability of the associated equilibrium states and the threshold phenomenon. Moreover, we also investigate the propagation property of solutions with initial data being a disturbance of one of the stable states which is confined to a half-line. We show that the more stable state will eventually dominate the whole dynamics and that the speed of this propagation (or invading process) is positive.     

Forearm ischemia decreases endothelial colony-forming cell angiogenic potential

Background aimsCirculating endothelial progenitor cells and especially endothelial colony-forming cells (ECFCs) are promising candidate cells for endothelial regenerative medicine of ischemic diseases, but the conditions for an optimal collection from adult blood must be improved.MethodsOn the basis of a recently reported vascular niche of ECFCs, we hypothesized that a local ischemia could trigger ECFC mobilization from the vascular wall into peripheral blood to optimize their collection for autologous implantation in critical leg ischemia. Because the target population with critical leg ischemia is composed of elderly patients in whom a vascular impairment has been documented, we also analyzed the impact of aging on ECFC mobilization and vascular integrity.ResultsAfter having defined optimized ECFC culture conditions, we studied the effect of forearm ischemia on ECFC numbers and functions in 26 healthy volunteers (13 volunteers ages 20–30-years old versus 13 volunteers ages 60–70 years old). The results show that forearm ischemia induced an efficient local ischemia and a normal endothelial response but did not mobilize ECFCs regardless of the age group. Moreover, we report an alteration of angiogenic properties of ECFCs obtained after forearm ischemia, in vitro as well as in vivo in a hindlimb ischemia murine model. This impaired ECFC angiogenic potential was not associated with a quantitative modification of the circulating endothelial compartment.ConclusionsThe procedure of local ischemia, although reulting in a preserved endothelial reactivity, did not mobilize ECFCs but altered their angiogenic potential.     

Arterial baroreflex function is an important determinant of acute cerebral ischemia in rats with middle cerebral artery occlusion

AIMS: To clarify whether arterial baroreflex function is an important determinant of acute cerebral ischemia in rats. MAIN METHODS: Three animal models were used in this study. In the first, saponin conjugated with substance P (SP-SAP) was injected into the nucleus tractus solitarii (NTS) of Sprague-Dawley (SD) rats to block the central baroreflex arc. In the second model, sinoaortic denervation (SAD) was performed to destroy the peripheral baroreflex arc in SD rats. In the third model, SD rats were divided into two groups according to their naturally occurring BRS values. After determining hemodynamic indexes and baroreflex sensitivity (BRS), we subjected the animals to middle cerebral artery (MCA) occlusion. Levels of interleukin (IL)-1beta and IL-6 were detected both in SAD/sham operation groups and low/high BRS groups. KEY FINDINGS: In all three animal models, baroreflex dysfunction significantly increased the infarct volume and weight. The levels of inflammatory factors were markedly elevated in SAD and low BRS groups. SIGNIFICANCE: These results demonstrate that the function of arterial baroreflex is an important determinant of acute cerebral ischemia in rats with MCA occlusion. Inflammation might be an important mechanism for the arterial baroreflex dysfunction-induced increase in brain damage in rats with MCA occlusion.     

Interaction between left ventricular wall motion and intraventricular flow propagation in acute and chronic ischemia

Myocardial ischemia has been associated with left ventricular (LV) postsystolic shortening. The combination of tissue Doppler imaging and high frame-rate acquisition of two-dimensional color flow makes it possible to study the interaction between LV wall motion and intraventricular flow propagation. The aim of this study was to examine in a clinical model the impact that acute myocardial ischemia and prior myocardial infarct might have on LV flow patterns and to explain the underlying mechanisms from the tissue Doppler data. LV flow propagation and tissue velocities during early diastole were studied in 18 healthy individuals, 17 patients with prior anterior myocardial infarct, and 16 patients before and during percutaneous coronary intervention (PCI) of the left anterior descending artery. Normal individuals had intraventricular flow propagation toward the apex during isovolumic relaxation. During this early diastolic time phase, myocardial velocities measured at mid- and apical septal segment were directed away from the apex. Before PCI, patients without myocardial infarction had similar findings as in normal individuals. In contrast, each patient with either prior myocardial infarction or PCI-induced acute ischemia had flow propagation opposite to normal individuals, and tissue velocities reversed toward the apex during early diastole. Reversal of early diastolic LV flow propagation in acute and chronic anterior myocardial ischemia reflects postsystolic shortening in the dyskinetic apical and septal myocardial segments.     

Cross-Language Opinion Lexicon Extraction Using Mutual-Reinforcement Label Propagation

There is a growing interest in automatically building opinion lexicon from sources such as product reviews. Most of these methods depend on abundant external resources such as WordNet, which limits the applicability of these methods. Unsupervised or semi-supervised learning provides an optional solution to multilingual opinion lexicon extraction. However, the datasets are imbalanced in different languages. For some languages, the high-quality corpora are scarce or hard to obtain, which limits the research progress. To solve the above problems, we explore a mutual-reinforcement label propagation framework. First, for each language, a label propagation algorithm is applied to a word relation graph, and then a bilingual dictionary is used as a bridge to transfer information between two languages. A key advantage of this model is its ability to make two languages learn from each other and boost each other. The experimental results show that the proposed approach outperforms baseline significantly.     

Finite element prediction of fatigue damage growth in cancellous bone

Cyclic stresses applied to bones generate fatigue damage that affects the bone stiffness and its elastic modulus. This paper proposes a finite element model for the prediction of fatigue damage accumulation and failure in cancellous bone at continuum scale. The model is based on continuum damage mechanics and incorporates crack closure effects in compression. The propagation of the cracks is completely simulated throughout the damaged area. In this case, the stiffness of the broken element is reduced by 98% to ensure no stress-carrying capacities of completely damaged elements. Once a crack is initiated, the propagation direction is simulated by the propagation of the broken elements of the mesh. The proposed model suggests that damage evolves over a real physical time variable (cycles). In order to reduce the computation time, the integration of the damage growth rate is based on the cycle blocks approach. In this approach, the real number of cycles is reduced (divided) into equivalent blocks of cycles. Damage accumulation is computed over the cycle blocks and then extrapolated over the corresponding real cycles. The results show a clear difference between local tensile and compressive stresses on damage accumulation. Incorporating stiffness reduction also produces a redistribution of the peak stresses in the damaged region, which results in a delay in damage fracture.     

Stability analysis of the partial selfing selection model

We undertake a detailed study of the one-locus two-allele partial selfing selection model. We show that a polymorphic equilibrium can exist only in the cases of overdominance and underdominance and only for a certain range of selfing rates. Furthermore, when it exists, we show that the polymorphic equilibrium is unique. The local stability of the polymorphic equilibrium is investigated and exact analytical conditions are presented. We also carry out an analysis of local stability of the fixation states and then conclude that only overdominance can maintain polymorphism in the population. When the linear local analysis is inconclusive, a quadratic analysis is performed. For some sets of selective values, we demonstrate global convergence. Finally, we compare and discuss results under the partial selfing model and the random mating model.     

全心缺血早期阶段室性心律失常仿真研究

为了分析全心缺血早期阶段对心脏电生理活动的影响,以及探讨诱发的室性心律失常机制,本研究考虑了缺血情况下高钾、酸液过多、局部缺氧的情况,结合详细的人类心室细胞生物物理上的动力学特征,开发了一个人体心室细胞和组织全心缺血模型.实验结果表明,全心缺血缩短了动作电位时程(action potential duration,APD),且减缓了兴奋的传导速率(conduction velocity,CV).同时,由于全心缺血降低了动作电位时程曲线(action potential duration restitution,APDR)斜率,且增大了有效不应期(effective refractory period,ERP),因此有利于维持折返波的稳定传导,使得室速不易转化为室颤.另一方面,尽管全心缺血导致了组织易感性的增加,但是由于其需要更长的异位刺激长度来保证折返波的形成,因此也在一定程度上降低了心律失常的发生概率.     

大鼠局灶性脑缺血后扩布性阻抑的发作及电针对其影响

目的：观察Wistar大鼠局灶性脑缺血后扩布性阻抑（SD）的发作情况及缺血后电针的影响。方法：线检法闭塞大鼠大脑中动脉,制备局灶性脑缺血模型。用神经电生理、神经病理等方法检测局灶性脑缺血后3h内SD发作情况及电针“合谷”穴（LI4）对SD的影响。结果：电针可减少局灶性脑缺血时SD的发作。结论：电针减少局灶性脑缺血时SD的发作,可能与电针缩小局灶性脑梗塞体积有关。