Responses of CDKs and p53 in Delayed Ischemic Neuronal Death

Stroke is a debilitating disease that affects millions each year.While in many cases cerebral ischemic in jury can be limited by effectivw resuscitation or thrombolytic treatment,the injured neurons wither in a process known as delayed neuronal death(DND).Mounting evidence indicates that DND is not simply necrosis played out in slow motion but apoptosis is triggered.Of particular interest are two groups of signal proteins that participate in apoptosis-cyclin dependent kinases(CDKs) and p53-among a myriad of signaling events after an ischemic insult.Recent investigations have shown that CDKs,a family of enzymes initially known for their role in cell cycle regulation,are activated in injured neurons in DND.As for p53,new reports suggest that its up-regulation may represent a failed attempt to rescue in jured neurons,although its up-regulation was previously considered an indication of apoptosis.These observations thus rekindle an old quest to identify new neuroprotective targets to minimize the stroke damage.In this review,the author will examine the evidence that indicates the participation of CDKs and p53 in DND and then introduce pre-clinical data to explore CDK inhibition as a potential neuroprotective target.Finally,using CDK inhibition as an example,this paper will discuss the pertinent criteria for a viable neuroprotective strategy for ischemic in jury.     

缺血性卒中复发与幽门螺杆菌感染的相关性

目的 探讨缺血性卒中复发与幽门螺杆菌（HP）感染的关系。方法 随机将77例首次卒中发作时HP阳性患者分为抗HP治疗组和对照组，观察其复发情况。同时观察139例首次卒中HP阴性患者复发时HP感染情况。结果 39例HP阳性患者经抗HP治疗后复发率为15．4％，38例HP阳性虱未抗感染治疗复发率为39．4％，139例首次卒中时HP阴性患者卒中复发率为24．5％（P＜0．05）；在33例首次卒中发作HP阴性者在复发时，其HP检测阳性者21例，阳性率为63．4％（P＜0．05）。结论 HP感染是缺血性卒中复发的独立危险因素，积极防治HP感染可以减少卒中发作。     

小剂量白蛋白治疗进展型脑梗死临床研究

目的：观察小剂量白蛋白治疗进展型脑梗死疗效及治疗前后血液流变学变化，方法：70例病人随机分为两组：治疗组35例和对照组35例，均应用脱水剂，脑细胞保护剂，保持水电酸碱平衡等常规治疗，治疗组35例脑梗死患者应用白蛋白5g静脉滴注，2次／d，连续10d为1疗程，治疗后15d复查血流变，结果：治疗组控制脑梗死进展的疗效明显高于对照组（P＜0．01），结论：小剂量白蛋白治疗进展型脑梗死有效。     

C-反应蛋白水平对急性缺血性脑卒中预后影响的系统评价

目的 应用Meta分析,评价C-反应蛋白(C-reactive protein,CRP)水平对急性缺血性脑卒中预后的影响.方法 计算机检索PubMed、MEDLINE(1991-2006)、中国学术期刊全文数据库(1979-2006)等.搜集CRP水平对急性缺血性脑卒中预后影响非随机对照研究,逐篇评价纳入文献的质量,采用RevMan4.2版软件进行Meta分析.结果 共纳入7篇文献(外文4篇,中文3篇),涉及841例患者.在急性缺血性脑卒中患者中,3个月以上随访截尾时间的死亡率和再发血管事件与CRP水平相关,CRP增高组发生率比CRP正常组分别高2.71和1.81倍[OR合并分别为3.71和2.81,95%CI分别为(2.40,5.73)和(1.42,5.53)]均有统计学意义(P＜0.05);CRP测量值与缺血性脑卒中复发和死亡亦相关,在复发患者中,CRP测量值平均高于未复发者为3.52 mg/L[WMD=3.52,95%CI(-0.01,7.05)],具有一定的临床意义;在死亡患者中,CRP测量值平均高于生存者为8.02 mg/L[WMD=8.02,95%CI(5.68,10.37)],具有统计学意义(P＜0.05).结论 发病时CRP的水平可以初步评价急性缺血性脑卒中患者的预后.     

Ischemia independent lesion evolution during focal stroke in rats

Lesion evolution during focal cerebral ischemia may depend on flow restrictions or on accumulation of toxic mediators within the infarct and expansion of these factors to the periinfarct region. So far, the precise contribution of flow dependent versus spreading-mediated impairment of viable periinfarct tissue has not been determined. Therefore, we measured lesion expansion, flow restrictions and glutamate distribution on serial brain sections at different time points after experimental focal ischemia.Permanent focal ischemia was induced by occlusion of the right middle cerebral artery in male rats and the flow reduction was subsequently measured at 1, 12 and 24 h using iodo[¹⁴C]antipyrine autoradiography. Additionally, the necrotic volume was determined on serial brain sections and the glutamate content was measured in tissue samples from adjacent microdissections.Twelve hours after focal ischemia no noteworthy viable areas with blood flow restrictions of 20-40 ml 100 g^− 1 min^− 1 existed but at 24 h the necrotic tissue exceeded the hemodynamically compromised region by 40 ± 21 mm³ (24%). Furthermore, at 12 and 24 h the glutamate content was elevated in areas surrounding the infarct.Relevant flow restrictions are detectable only during early stages of infarct maturation, whereas the propagation of secondary factors may be the predominant mechanism for delayed infarct evolution.     

The association of post-stroke neurological improvement with risk of subsequent deterioration due to stroke events

We sought to simultaneously confirm that substantial recovery at day 1 and day 7 after acute ischaemic stroke onset is associated with subsequent neurological deterioration in patients of the Acute Stroke Therapy by Inhibition of Neutrophils randomized clinical trial. Substantial recovery was assessed by improvement in the National Institutes of Health Stroke Score (NIHSS). Neurological deterioration was defined as any stroke event or NIHSS worsening from recovery assessment to day 90. After adjusting for age, t-PA and day 1 NIHSS, there was a non-significant tendency of substantial (pre-specified as 75%) recovery at day 1 to be associated with later deterioration [odds ratio (OR) 2.47; 95% CI, 0.95–6.50]. The corresponding OR for substantial (pre-defined as 65%) recovery at day 7 was 1.84 (0.85–3.96). Other thresholds for recovery were significantly associated with later deterioration: >50%, 80%, 90% and 100% for day 1 and >50%, 60%, 70%, 90% and 100% for day 7. The effect of recovery at day 1 was more important than that of later recovery. This study confirms the association between recovery and subsequent neurological deterioration and is the first to indicate the greater importance of acute recovery at day 1 in comparison with later recovery.     

Alberta早期CT评分的临床应用

超早期溶栓被公认为脑血栓形成最有效的治疗手段，但是，什么样的患者最适合溶栓治疗，目前还没有一种公认的标准。有学者提出用一种基于CT早期缺血性改变的半定量方法——Alberta早期CT评分（ASPECTS）来选择适合溶栓治疗的患者。ASPECTS是一种仅适用于评价大脑中动脉（MCA）供血区缺血改变的量表，其总分为10分。ASPECTS=10分提示MCA供血区无早期缺血征象，ASPECTS=0分表示MCA供血区广泛缺血，提示MCA主干闭塞。多数学者认为，ASPECTS〉7分的患者是溶栓治疗的最佳候选者，而当ASPECTS≤7分时，溶栓治疗不但不能改善症状，反而会增高颅内出血的风险。然而，对ASPECTS的溶栓治疗选择标准仍然存在一些不同的看法，文章就ASPECTS的具体操作及其在临床实践中的应用进行了综述。     

Pathophysiological aspects of brain edema

Summary Two mayor types of brain edema, related to two different pathomechanisms, can be recognized: 1)cytotoxic type-where the main feature is the swelling of cellular elements of brain parenchyma and 2)vasogenic type-where an increased vascular permeability leading to accumulation of edema fluid inthe extracellular spaces plays the principal role. In this type of edema, there is a close interrelationship between extravasation of serum proteins and retention of water in the brain tissue. In theischemic brain edema both cytotoxic and vasogenic mechanisms are involved. A biphasic opening of the blood-brain barrier, associated with vasogenic edema, is observed following release of major cerebral artery occlusion. The first opening of the barrier is related to a reactive hyperemia which follows promptly recirculation. The second opening, recognizable after a delay, is associated with a severe ischemic brain tissue injury.Dedicated to Prof. F. Seitelberger on the occasion of his seventieth birthday     

脑出血后血肿周围组织的磁共振灌注成像研究

目的:利用磁共振灌注成像观察脑出血后组织血流动力学变化,并对其机制和意义进行初步探讨。方法:10例发病2周以内脑出血患者行磁共振动态磁化增强灌注成像。6例发病24h脑出血患者行流动敏感交互式反转恢复(FAIREST)磁共振灌注成像。结果:血肿周围MTT较对侧延长,平均延长(0.458±0.945)s(P<0.01),MTT延长与血肿体积无明显相关性(r=0.32,P=0.08)。6例行FAIREST灌注成像2例血肿周围CBF较对侧明显减低,3例变化不明显,1例上升。结论:本组磁共振灌注成像未发现脑出血周围组织不可逆转的缺血,但存在血肿周围组织血量减少。FAIREST技术有一定的临床实用价值。