Intracerebral distribution of albumin after transient cerebral ischemia: light and electron microscopic immunocytochemical investigation

Summary The blood-brain barrier breaks down following cerebral ischemia, but the exact sequence of events for extravasation of serum proteins and their parenchymal distribution remain uncertain. We studied the distribution of serum albumin in the hippocampus of the gerbil brain using light and electron microscopic immunocytochemical techniques. With light microscopy, there was no reaction for albumin for the first 12 h after unilateral common carotid artery occlusion for 10 min and reperfusion. At 12 h, the reaction was weak and limited to the neuropil in the subiculum-CA1 region (between the subiculum and the medial CA1 region). After 24 h, the reaction became intense in the neuropil and neuronal perikarya in the subiculum-CA1 and medial CA1 regions. The electron microscopic immunocytochemical study of the subiculum-CA1 and medial CA1 regions revealed electron-dense immunoprecipitates in the extracellular space and the peripheral part of the apical dendrites as early as 30 min after reperfusion and in the astrocytic cytoplasm after reperfusion for 1 h. However, immunoprecipitates were not found in the neuronal perikarya until after reperfusion for 24 h. The present study demonstrated prompt appearance of albumin in the extracellular space of the brain parenchyma after re-establishment of cerebral circulation and prompt accumulation in the peripheral part of the dendrites with spreading to neuronal perikarya, likely in the process of degeneration and death.Supported by the grant NS-06663 from the National Institutes of Health, U. S. Public Health Service     

Inhibition of glutamate release in rat hippocampus by kynurenic acid does not protect CA1 cells from forebrain ischemia

We assessed the effect of a broad spectrum glutamatergic receptor antagonist, kynurenic acid (500 mg/kg) on ischemia-induced hippocampal glutamate release and neuronal damage. Kynurenic acid significantly decreased glutamate release during ischemia but had no effect on the hippocampal lesion. Some protection was observed in the cortex and in the striatum. These data suggested that the extracellular accumulation of glutamate during forebrain ischemia does not play a major role in the hippocampus.     

Rapid monitoring of changes in water diffusion coefficients during reversible ischemia in cat and rat brain

Changes in the diffusion constant of water during reversible brain ischemia and cardiac arrest were monitored with a 10-s time resolution. Results (five cats, three rats) indicate that these changes are reversible and that the bulk of the changes are not caused by temperature or motion related to brain pulsations and blood flow. The rapid time course of the changes corresponds to the known time course for changes in energy state, signal transduction, and ionic homeostasis.     

Haemodynamic studies in early stroke

Summary We investigated prospectively a consecutive series of 81 patients suffering from acute middle cerebral artery (MCA) ischaemia by transcranial Doppler ultrasonography (TCD) within 24 h of the onset of symptoms. To monitor the haemodynamic changes follow-up recordings were carried out at short intervals during the next 2–3 weeks until stable haemodynamic status was achieved. In order to estimate the value of early TCD examinations in predicting the extent of brain damage seen later on, initial MCA flow reduction was correlated with infarction size and pattern on computed tomography. Fifty-three cases showed sufficient ultrasound penetration through the temporal bone. MCA flow asymmetries were recorded in 45 patients (85%); occlusion was observed in 17. Recanalization occurred in 11 patients followed by transient hyperaemia in 3, leaving residual stenosis in 2. Initial increase of flow velocities normalized within days or weeks in 7 out of 9 patients, while 2 developed residual MCA stenosis. Nineteen patients showed a considerable flow reduction on admission, which returned to normal in 9; transient hyperaemia was detected in 5 of these. Eight patients did not show any MCA flow asymmetry. Our study revealed very variable haemodynamic changes in acute stroke, which influenced further diagnostic and therapeutic management. The high rate of spontaneous recanalizations of MCA occlusions followed by transient hyperaemia in many cases has an important bearing on thrombolytic or theological therapy. Flow velocity differences could be related to infarction pattern rather than to infarction volume. Early MCA flow asymmetry recorded by TCD within the first 24 h could not reliably predict the extent of persistent brain damage or clinical outcome.     

Human brain atlas: For high-resolution functional and anatomical mapping

We present the new computerized Human Brain Atlas (HBA) for anatomical and functional mapping studies of the human brain. The HBA is based on many high-resolution magnetic resonance images of normal subjects and provides continuous updating of the mean shape and position of anatomical structures of the human brain. The structures are transformable by linear and nonlinear global and local transformations applied anywhere in 3-D pictures to fit the anatomical structures of individual brains, which, by reformatting, are transformed into a high-resolution standard anatomical format. The power of the HBA to reduce anatomical variations was evaluated on a randomized selection of anatomical landmarks in brains of 27 young normal male volunteers who were different from those on whom the standard brain was selected. The HBA, even when based only on standard brain surface and central structures, reduced interindividual anatomical variance to the level of the variance in structure position between the right and left hemisphere in individual brains. © 1994 Wiley-Liss, Inc.     

不同剂量普伐他汀治疗急性脑梗死的疗效和安全性研究

目的：探讨不同剂量普伐他汀在脑梗死急性期治疗的可行性、降脂疗效及安全性。方法：脑梗死急性期病人146例，随机分为3组，A组（50例）为对照组，B组（49例）每晚服普伐他汀10mg，C组（47例）每晚服普伐他汀20mg，观察30d。比较治疗前后血脂、神经功能缺损评分、生化指标等变化，并记录服药后不良反应。结果：各组总胆固醇（TC）、低密度脂蛋白（LDL-C）、超敏C-反应蛋白（hs-CRP）在治疗后都有所下降，C组下降最显著，B组次之，A组下降程度较小。A组TG治疗前后无明显变化，B组和C组TG治疗后有所下降，两组间无明显差别。脂蛋白（Lpa）在A组治疗后有下降，B组无明显变化，C组较前轻度升高。各组治疗前后神经功能缺损评分均有降低，但各组之间比较无明显差异（P〉0.05）。观察期间所有病人均能耐受普伐他汀，治疗前后肝、肾功能、肌酸激酶（CK）等无明显变化。结论：在脑梗死急性期应用普伐他汀（每日10～20mg）是安全可行的，且每日20mgTC、TG降低更显著，脑梗死急性期的病人应用普伐他汀后取得较好的降脂疗效，神经功能缺损评分的改善有待较长期观察。     

大鼠脑干缺血模型制备及早期超微结构观察

目的:制备脑干缺血动物模型并观察大鼠脑干缺血后早期组织学病理的超微结构。方法:应用两点电凝基底动脉的方法制作鼠脑干缺血动物模型。结果:病理学观察发现脑干缺血2小时即可出现超早期病理变化,并随时间的延长缺血性损害逐渐加重。结论:两点电凝基底动脉后可以造成稳定的脑干缺血,对急性脑干缺血的病理学研究有一定的价值。     

脑梗死后早发性癫(癎)发作临床特点分析

目的:探讨脑梗死(CI)后早发性癫癎发作(EES)的临床特点。方法:对2643例确诊为CI患者的临床资料进行回顾性研究。结果:CI后EES的发生率为4.58%,女性高于男性(P<0.05);婴幼儿及未成年人高于成年人(P<0.01)和老年人(P<0.01);累及皮质的发生率高于未累及皮质的(P<0.01);EES作为CI首发症状者占49.59%,24h内出现者占76.03%,1周内出现者占94.21%,仅有5.79%在第2周出现;局灶性发作占65.29%,全面性发作占34.71%;给予AEDs治疗发作均可控制,伴有EES的患者病死率高于不伴有者(P<0.05)。结论:CI后EES较为常见,女性多于男性,未成年人的发生率高于成年人及老年人,与梗死部位有关,以局灶性发作为主,抗癫癎治疗有效,临床预后较差。     

Pharmacologic preconditioning effects: Prostaglandin E1 induces heat-shock proteins immediately after ischemia/reperfusion of the mouse liver

Prostaglandin E1 (PGE1) has several potential therapeutic effects, including cytoprotection, vasodilation, and inhibition of platelet aggregation. This study investigates the protective action of PGE1 against hepatic ischemia/reperfusion injury in vivo using a complementary DNA microarray. PGE1 or saline was continuously administered intravenously to mice in which the left lobe of the liver was made ischemic for 30 minutes and then reperfused. Livers were harvested 0, 10, and 30 minutes postreperfusion. Messenger RNA was extracted, and the samples were labeled with two different fluorescent dyes and hybridized to the RIKEN set of 18,816 full-length enriched mouse complementary DNA microarrays. Serum alanine aminotransferase and aspartate aminotransferase levels at 180 minutes postreperfusion were significantly lower in the PGE1-treated group than in the saline-treated group. The cDNA microarray analysis revealed that the genes encoding heat-shock protein (HSP) 70, glucose-regulated protein 78, HSP86, and glutathione S-transferase were upregulated at the end of the ischemic period (0 minutes postreperfusion) in the PGE1 group. Our results suggested that PGE1 induces HSPs immediately after ischemia reperfusion. HSPs might therefore play an important role in the protective effects of PGE1 against ischemia/reperfusion injury of the liver.     

New Insights into the Pathogenesis and the Therapy of Recurrent Focal Glomerulosclerosis

Recurrent focal glomerulosclerosis (FSGS) in renal allografts has remained a frustrating and enigmatic disease. Recent studies on gene mutations encoding podocin and other components of the slit-diaphragm in patients with native kidney nephrotic syndrome have underscored the heterogenecity of the idiopathic form of FSGS. While familial FSGS rarely recurs following transplantation, the sporadic variety of FSGS is associated with a 30% recurrence rate. The patients with the sporadic variety of FSGS who have homozygous or complex heterozygous podocin mutations have a low recurrence rate. In the other patients with sporadic FSGS, a more complex and likely multifactorial etiology accounts for the recurrence of FSGS. The role of CD80 expression on podocytes is intriguing but requires confirmation in kidney biopsies of patients with recurrent FSGS. Recent findings on podocin genomics, the permeability factor and CD80 expression may ultimately lead to a better understanding of recurrent FSGS as well as a more effective approach to its prevention and treatment.