缺血再灌注损伤的保护——预处理到后处理的哲学思考

缺血预处理定减轻缺血再灌注损伤的有效措施,是事物矛盾性的具体体现。缺血预处理把矛盾两个对立面统一起来,将损伤（缺血）转化为战胜损伤（减轻缺血再灌注损伤）的有效手段,同时缺血预处理也是外因和内因两者作用的辩证统一。缺血后处理是近年发现的能减轻缺血再灌注损伤的有效措施,在缺血后处理中亦体现了矛盾的对立统一规律及外因和内因两者相互作用的辩证统一规律。     

缺血预处理与细胞凋亡的研究进展

缺血预处理是通过预先短暂缺血来延缓或减轻组织后续缺血再灌注损伤的现象,是机体的一种内源性保护机制.近来发现缺血预处理可以减轻靶器官的细胞凋亡,其机制可能涉及了复杂的信号传导途径和凋亡相关基因的变化.     

缺血预处理与细胞凋亡的研究进展

缺血预处理是通过预先短暂缺血来延缓或减轻组织后续缺血再灌注损伤的现象,是机体的一种内源性保护机制。近来发现缺血预处理可以减轻靶器官的细胞凋亡,其机制可能涉及了复杂的信号传导途径和凋亡相关基因的变化。     

SAFE通路参与缺血后处理心肌保护作用机制的探讨

缺血后处理(ischemic postconditioning,IPost)是在心肌缺血后持续再灌注前给予多次短暂的再灌注/缺血处理的处理方法,对心肌缺血/再灌注损伤有着重要的保护作用.其心肌保护的具体机制十分复杂,尚未完全阐明.生存活化因子增强(survivor activating factor enhancement,SAFE)途径是IPost中新近发现的保护通路,阐明其在IPost心肌保护中的作用,将为寻找新的药物治疗靶点提供新思路.     

肝脏缺血预处理研究中的哲学思考

1　预处理研究与原型启示1 1　预处理发展史1 986年 ,Ｍｕｒｒｙ等首次报道结扎犬冠状动脉 5ｍｉｎ,再灌注 1 0ｍｉｎ ,重复进行 4次 ,不仅未产生累加性缺血损伤 ,反而可以减轻随后 45ｍｉｎ缺血所致的心肌损伤 ,他们将心脏遭受短暂缺血后能耐受随后较长时间缺血损伤的现象称为缺血预处理 (ｉｓ ｃｈｅｍｉｃｐｒｅｃｏｎｄｉｔｉｏｎｉｎｇ ,ＩＰＣ) [1] 。该现象已在不同种属动物与临床病人以及不同的实验模型 (在体心脏、离体心脏、培养的心肌细胞)、心脏以外组织器官(如肝、小肠、大脑、视网膜 )得到证实[2 ] 。整体动物进行肝脏缺血预…     

SAFE通路参与缺血后处理心肌保护作用机制的探讨

缺血后处理(ischemic postconditioning,IPost)是在心肌缺血后持续再灌注前给予多次短暂的再灌注/缺血处理的处理方法,对心肌缺血/再灌注损伤有着重要的保护作用。其心肌保护的具体机制十分复杂,尚未完全阐明。生存活化因子增强(survivor activating factor enhancement,SAFE)途径是IPost中新近发现的保护通路,阐明其在IPost心肌保护中的作用,将为寻找新的药物治疗靶点提供新思路。     

缺血预处理概念是创造性思维的杰作

1　缺血预处理概念是创造性思维的产物1 1　缺血预处理 (ＩＰ)的概念是由Ｍｕｒｒｙ等提出的。 1986年Ｍｕｒｒｙ等[1 ] 直接结扎大的冠状动脉回旋支 4次 ,各 5分钟 ,每次间隔 5分钟再灌注 ,即缺血预处理 ,然后再阻断冠脉血流 40分钟 ,心肌梗塞面积约为 2 3% ,而对照组 (单纯阻断冠脉 40分钟 ) ,心肌梗塞面积约为 2 9 4% ,即经ＩＰ后缩小心梗面积 75 %左右 (Ｐ <0 .0 0 1) ,第一次在犬的心脏证明了ＩＰ能缩小心梗范围。1 2　传统观点认为 ,短暂心肌缺血会造成心肌可逆性损伤 ,并使心肌更难以耐受再次缺血损伤的打击 ,这一观点在相当一段时间…     

血管紧张素转换酶抑制剂与心肌缺血再灌注的细胞凋亡

随着心脏外科手术和介入治疗技术的进展以及心肌缺血患者的增加,心肌缺血再灌注损伤成为临床工作一种常见的病理生理过程.如何采用有效的治疗手段进行心肌保护,防治或降低缺血再灌注所造成的损伤,一直是心脏科学探索的一个重要课题.血管紧张素转化酶抑制剂对很多心脏疾病的治疗特别是拟行心脏手术患者的治疗都取得了良好的效果.随着对其研究的进展,其预处理可为临床预防治疗心肌缺血再灌注损伤提供思路与方法.     

血管紧张素转换酶抑制剂与心肌缺血再灌注的细胞凋亡

随着心脏外科手术和介入治疗技术的进展以及心肌缺血患者的增加,心肌缺血再灌注损伤成为临床工作一种常见的病理生理过程。如何采用有效的治疗手段进行心肌保护,防治或降低缺血再灌注所造成的损伤,一直是心脏科学探索的一个重要课题。血管紧张素转化酶抑制剂对很多心脏疾病的治疗特别是拟行心脏手术患者的治疗都取得了良好的效果。随着对其研究的进展,其预处理可为临床预防治疗心肌缺血再灌注损伤提供思路与方法。     

对适应性细胞保护的辩证思考

细胞遭受非致命的损伤刺激后能对随后更大的损伤产生防御和保护作用,这种现象被称为适应性细胞保护。损伤和抗损伤是疾病发展过程中一对基本矛盾,机体细胞具有内源性抗损伤机制。采用非致命性损伤刺激作为预处理的手段,从而调动细胞的适应性保护能力,将给有关疾病的防治提供新的应用前景。预适应手段和细胞内源性抗损伤机制两者是外因和内因的辩证统一,存在因果关系的多样性。同时,适应性细胞保护也有其相对的一面,表现为种属相对性和保护能力的相对性。     

Stuttering due to ischemic stroke

Acquired stuttering is a disorder of the fluency of speech. The mechanism underlying stuttering is unknown. It may occur after bilateral and unilateral cortical or subcortical brain damage. We report two cases who had stuttering resulting from left parietal infarction.     

Neuroprotection and the ischemic cascade

Brain ischemia is a process of delayed neuronal cell death, not an instantaneous event. The concept of neuroprotection is based on this principle. Diminished cerebral blood flow initiates a series of events (the "ischemic cascade") that lead to cell destruction. This ischemic cascade is akin to a spreading epidemic starting from a hypothesized core of ischemia and radiating outward. If intervention occurs early, the process may be halted. Interventions have been directed toward salvaging the ischemic penumbra. Hypothermia decreases the size of the ischemic insult in both anecdotal clinical and laboratory reports. In addition, a wide variety of agents have been shown to reduce infarct volume in animal models. Pharmacologic interventions that involve thrombolysis, calcium channel blockade, and cell membrane receptor antagonism have been studied and have been found to be beneficial in animal cortical stroke models. Human trials of neuroprotective therapies have been disappointing. Other than thrombolytics, no agents have shown an unequivocal benefit. The future of neuroprotection will require a logical extension of what has been learned in the laboratory and previous human trials. A sensible approach to the use of multiple-agent cocktails used in combination with thrombolytics is likely to offer the highest chance for benefit.     

一氧化氮在新生儿缺氧缺血性脑病中的作用

在围产期窒息引起的新生儿缺氧缺血性脑病（HIE）中,一氧化氮（NO）对脑组织具有神经保护性和神经毒性双重效应,这取决于NO的来源。并且NO与谷氨酸及内皮素（ET）相互作用。应用哲学观点深入研究NO的作用机制对于探讨HIE的防治具有重要意义。     

一氧化氮在新生儿缺氧缺血性脑病中的作用

在围产期窒息引起的新生儿缺氧缺血性脑病(HIE)中,一氧化氮(NO)对脑组织具有神经保护性和神经毒性双重效应,这取决于NO的来源.并且NO与谷氨酸及内皮素(ET)相互作用.应用哲学观点深入研究NO的作用机制对于探讨HIE的防治具有重要意义.     

Risk factors for arterial ischemic stroke in childhood

Stroke affects up to 13 of 100,000 children, is more common in boys and African Americans, and is associated with considerable cognitive and psychiatric morbidity, as well as motor disability. Around half are hemorrhagic and half are ischemic. Underlying conditions include sickle cell disease, cardiac abnormalities, chromosomal abnormalities (eg, Down syndrome), and neurocutaneous conditions (eg, neurofibromatosis), but up to half the patients with ischemic stroke have no previously diagnosed condition. Although there is almost certainly an important genetic component to stroke risk, head trauma, infections, drugs and radiation appear to play an etiological role in some patients. The majority of the patients with infarction in an arterial distribution have associated cerebrovascular disease. Vascular pathologies include carotid or vertebrobasilar dissection, intracranial vasculopathy affecting the middle and anterior cerebral arteries, which is often transient, and moyamoya. Intermediate risk factors may include hypertension, hypoxia, and poor nutrition leading, for example, to iron deficiency and hyperhomocysteinemia. Some chronic conditions may directly influence the child's behavior and stroke recurrence risk, although large cohorts and randomized controlled trials will be needed before strategies for modification can be evidence-based.     

Motor performance improved by exercises in cerebral ischemic rats

Physical exercise may induce neuroprotective effects against brain damage after stroke. The authors aimed to investigate the effects of various exercises on motor function, striatal angiogenesis, and infarct volume in cerebral ischemic rats. Adult male Sprague Dawley rats were subjected to middle cerebral artery occlusion and randomly assigned to 1 of the 4 groups: Rota-rod training, lower speed treadmill training, higher speed treadmill training, or no exercise control. Motor function, striatal angiogenesis, and infarct volume were evaluated before or after motor training. After training, motor function and striatal angiogenesis changed significantly in Rota-rod and higher speed treadmill training groups as compared with the control group. Improvement in motor function significantly correlated with striatal angiogenesis after motor training. Infarct volumes were significantly decreased in lower and higher speed treadmill training groups. The results indicated that both motor training procedures can be used as effective training programs in stroke rehabilitation.     

The neural underpinnings of facial emotion recognition in ischemic stroke patients

Deficits in facial emotion recognition occur frequently after stroke, with adverse social and behavioural consequences. The aim of this study was to investigate the neural underpinnings of the recognition of emotional expressions, in particular of the distinct basic emotions (anger, disgust, fear, happiness, sadness and surprise). A group of 110 ischaemic stroke patients with lesions in (sub)cortical areas of the cerebrum was included. Emotion recognition was assessed with the Ekman 60 Faces Test of the FEEST. Patient data were compared to data of 162 matched healthy controls (HC’s). For the patients, whole brain voxel-based lesion–symptom mapping (VLSM) on 3-Tesla MRI images was performed. Results showed that patients performed significantly worse than HC’s on both overall recognition of emotions, and specifically of disgust, fear, sadness and surprise. VLSM showed significant lesion–symptom associations for FEEST total in the right fronto-temporal region. Additionally, VLSM for the distinct emotions showed, apart from overlapping brain regions (insula, putamen and Rolandic operculum), also regions related to specific emotions. These were: middle and superior temporal gyrus (anger); caudate nucleus (disgust); superior corona radiate white matter tract, superior longitudinal fasciculus and middle frontal gyrus (happiness) and inferior frontal gyrus (sadness). Our findings help in understanding how lesions in specific brain regions can selectively affect the recognition of the basic emotions.     

Global cognitive function before,surrounding, and after ischemic stroke: the role of risk and protective factors varies with time among ischemic stroke survivors

An estimated 65% of individuals demonstrate multidomain cognitive impairment poststroke, although little is known about the varying role of cognitive risk and protective factors in preischemic, peri-ischemic, and postischemic stroke phases. Longitudinal changes in global cognitive function after ischemic stroke are not well characterized, especially in older adults over age 80. We examined global cognitive function trajectories in these three phases across a mean follow-up of 8.12 (2.30) years in 159 female stroke survivors aged 65–79 at baseline using linear mixed models with change points. In separate models controlling for demographic variables, we tested the interaction of baseline risk and protective factors with stroke phase on global cognitive function. None of the prestroke global cognitive function means or trajectories differed significantly. At the time of ischemic stroke, higher body mass index (BMI), the presence of hypertension (HTN), low optimism, and higher physical function were all associated with significantly greater mean decreases in global cognition (all p’s <.0.0001), but were not significantly different from the contrasting level (all p’s >0.05). Higher BMI, the presence of HTN, low optimism, and higher physical function were in turn protective of global cognitive decline postischemic stroke (all contrasting p values <.01). Baseline factors may play either a risk or a protective role in global cognitive function depending on the phase of ischemic stroke.     

Psychological factors and depressive symptoms in ischemic heart disease.

The aim of this study was to determine whether learned helplessness, cognitive distortions, self-efficacy, and dispositional optimism assessed at Time 1 (T1; questionnaires mailed at 1 month postdischarge) would predict depressive symptoms at Time 2 (T2; questionnaires mailed at 1-year follow-up) in a sample of 86 patients hospitalized with ischemic heart disease. Multiple regression results indicated that optimism and cognitive distortions at T1 were significantly associated with T1 depressive symptoms after controlling for confounding variables. When the T1 psychological factors were analyzed with T2 depressive symptoms, only optimism continued to predict depressive symptoms after controlling for confounds and T1 depressive symptoms. The global expectancies that optimism assessed appeared to be more stable over time than the statelike beliefs of cognitive distortions and may have accounted for why optimism predicted T2 depressive symptoms.     

Working memory outcomes following unilateral arterial ischemic stroke in childhood

There is a dearth of research examining working memory (WM) following pediatric arterial ischemic stroke (AIS). This study assesses the WM patterns of 32 children, aged 6 to 14 years, with a history of unilateral AIS and 32 controls using a paradigm based on Baddeley and Hitch’s multi-component WM model. The results indicate compromised WM in children with AIS relative to controls and parent reports confirm higher rates of dysfunction. Supplementary analyses of impairment confirm higher rates in children with AIS, ranging from 31.25% to 38.70% on performance-based measures and 50.00% on parent reports, compared to 0.00% to 21.88% on performance-based measures in controls and 15.63% on parent reports. Continual follow-up is recommended given that a subset of children with stroke appear to be at risk for WM impairment. Moreover, the subtle nature of WM challenges experienced by many children who have experienced a stroke increases the likelihood that WM impairment could go undetected. The long-term trajectories of WM in the pediatric stroke population remains unknown and future studies are needed to track changes in WM functioning over time.