Age-Related Changes in Ceruloplasmin Content in W/SSM Rats

We studied enzyme systems (lactate dehydrogenase) of mitochondria in cerebral nerve cells in experimental encephalopathy developing after thermal injury. In animals receiving neuromedin at the early terms after injury, the ratio of forward to reverse lactate dehydrogenase reactions significantly increased over the first day after injury and returned to normal on day 7. __________ Translated from Byulleten' Eksperimental'noi Biologii i Meditsiny, Vol. 145, No. 6, pp. 626–627, June, 2008     

Early induction of neuronal lipocalin-type prostaglandin D synthase after hypoxic-ischemic injury in developing brains

Lipocalin-type prostaglandin (PG) D synthase (L-PGDS) is up-regulated in oligodendrocytes (OLs) in mouse models for genetic neurological disorders including globoid cell leukodystrophy (twitcher) and GM₁ and GM₂ gangliosidoses and in the brain of patients with multiple sclerosis. Since L-PGDS-deficient twitcher mice undergo extensive neuronal death, we concluded that L-PGDS functions protectively against neuronal degeneration. In this study, we investigated whether L-PGDS is also up-regulated in acute and massive brain injury resulting from neonatal hypoxic-ischemic encephalopathy (HIE). Analysis of brains from human neonates who had died from HIE disclosed that the surviving neurons in the infarcted lesions expressed L-PGDS. Mouse models for neonatal HIE were made on postnatal day (PND) 7. Global infarction in the ipsilateral hemisphere was evident at 24 h after reoxygenation in this model. Intense L-PGDS immunoreactivity was already observed at 10 min after reoxygenation in apparently normal neurons in the cortex, and thereafter, in neurons adjacent to the infarcted area. Quantitative RT-PCR revealed that the L-PGDS mRNA level of the infarcted hemisphere was 33-fold higher than that of the sham-operated mouse brains at 1 h after reoxygenation and that it decreased to the normal level by 24 h thereafter. Furthermore, in both human and mouse brains, many of L-PGDS-positive cells were also immunoreactive for p53; and some of these expressed cleaved caspase-3. The expression of L-PGDS in degenerating neurons implies that L-PGDS functions as an early stress protein to protect against neuronal death in the HIE brain.     

Dynamics of formation of primary and secondary lipid peroxidation products upon copper-dependent oxidation of low-density lipoproteins isolated from blood serum of patients with ischemic heart disease

The kinetics of copper-induced oxidation of lipids in serum low-density lipoproteins from healthy subjects and patients with ischemic heart disease and documented coronary atherosclerosis is studied. After a 4-h incubation with 40 μM CuSO₄, the oxidizability of patients' lipoproteins is higher, judging from the contents of diene conjugates and oxidation products reacting with thiobarbituric acid. Intergroup differences in the kinetics of the diene conjugate formation are revealed. Statistical analysis shows that in all studied individuals there is no relationship between the oxidizability of low-density lipoproteins and the cholesterol content in lipoproteins and serum. Translated fromByulleten' Eksperimental'noi Biologii i Meditsiny, Vol. 122, No. 7, pp. 32–36, July, 1996     

Case report: human herpesvirus 7 associated fatal encephalitis in a peripheral blood stem cell transplant recipient

Previous studies have suggested a neuroinvasive and neuropersistent potential of human herpesvirus 7 (HHV-7). In this report, a case of fatal encephalitis is described and its association with HHV-7 infection is discussed. An 8-year-old girl received a peripheral blood stem cell transplant for relapsed acute lymphoblastic leukaemia. The post-transplant period was uneventful and a course of intrathecal chemotherapy was given on Day-30. On Day-41, she developed acute encephalopathy with diplopia and nystagmus. She ran a rapid downhill course and succumbed despite antiviral treatment. The only positive pathological finding was the multiple microscopic foci of haemorrhage associated with neuronal degeneration detected in the brain stem. All microbiological investigations were negative, except for the presence of HHV-7 DNA in cerebrospinal fluid and brain stem tissue samples.     

Pathological Effects of Matebrnal Hypoglycemia on Fetal Development in Cats

The pathogenesis of fetal brain damage caused by acute maternal hypoglycemia was investigated experimentally in cats: profound hypoglycemia (blood glucose concentration:less than 30 mg/dl) was induced in 12 pregnant cats at various stages of gestation by intravenous bolus injections of insulin. Maximal hypoglycemia was attained within 2 3 h, although the grade and duration in individual cats varied. The EEGs of all of seven maternal cats examined showed an increased frequency of slow high-voltage waves as hypoglycemia progressed, eventually becoming flat in 3 for a maximum period of 20 min. Some fetuses showed severe neuropathological changes, such as infarction or intrauterine death. Subventricular soften ing, cortical hemorrhage and ischemic neuronal changes also occurred, being distributed symmetrically in the para-sagittal areas of the cerebrum, basal ganglia, thalamus and tegrnentum of the brainstem. In general, these patho logical changes were more marked in fetuses and neonates than in the maternal cats, in which only ischemic neuronal changes were present, and may have been due to fetal systemic hypotension and cerebral ischemia induced by hypoglycemia. In maternal cats, the distribution of neu rons showing ischemic changes was widest in the cerebral cortex, and some were also present in the dentate gyri of the hippocampus. Moreover, ultrastructural examination of the ischemic neurons in maternal cats, unlike those of the fetuses, showed no mitochondrial swelling. Therefore, the distribution and ultrastructural nature of the ischemic neurons found in the maternal cats were considered to be characteristic of hypoglycemia, as proposed by Agardh et al . (1980). Acta Pathol Jpn 42 : 316–324, 1992.     

Use of Transcranial Magnetic Stimulation with Measurement of Motor Evoked Potentials in the Acute Period of Hemispheric Ischemic Stroke

Functional derangements in the brain during the acute period of ischemic hemispheric stroke (IS) were assessed in terms of the severity of the motor neurological deficit in the acute period of IS and neurophysiological measures of motor evoked potentials (MEP) using transcranial magnetic stimulation (TCMS). A total of 52 patients (23 women, 29 men, mean age 58.5 ± 8.7 years) were studied. Patients were divided into two subgroups: group 1 consisted of 29 patients with good functional outcomes from the acute period; group 2 consisted of 23 patients with poor functional outcomes. The use of TCMS for recording MEP demonstrated increases in the latency of the M response both after stimulation of the projection of the motor area of the cortex of the lesioned hemisphere and after stimulation of the spinal cord. There were increases in the central motor conduction time (CMCT) in the lesioned hemisphere of the brain and a negative correlation was seen between the severity of the neurological defect and CMCT on the one hand (r = –0.65 to –0.78; p < 0.001) and, on the other, the latency of the M response in TCMS of the motor zone of the cortex on the side of the hemispheric stroke (r = –0.65 to –0.79; p < 0.001). The increases in the latency of the M response and CMCT have prognostic significance for early assessment of the outcome of IS.     

In vitro biosynthesis of plasma proteins under ischemic conditions of closed-circuit perfusion of healthy and intoxicated rabbit liver

We are elaborating on the kinetics and mechanisms of septic rabbit liver to de novo biosynthesize acute-phase response (APR) proteins under in vitro conditions of deepening ischemia in reference to their in vivo prevalence in serum and cerebrospinal fluids (CSF) collected at predetermined times. The significance of the data is interpreted as relevant to grafting cadaveric liver into end-stage liver diseased patients and APR-induced ischemic heart diseases (IHD). Hepatic APR was induced by CCl(4)-intubation, and the administration of cholera toxin (CT) or scorpion venom (SV), or both, to rabbits. Hepatic functional efficiency, in terms of biosynthesis of APR proteins in closed circuit perfusion of the isolated intoxicated liver with oxygenated saline or L-15 media paralleled the two-dimensional immunoelectrophoresis (2D-IEP) spectrum of APR serum proteins at time of liver isolation. We are suggesting: (a) in vitro biosynthesis of plasma proteins by isolated perfused liver is the result of in vivo decoded and retained APR inflammatory signals; and (b) decoded inflammatory signals are expressed not withstanding the perfusate's organic composition. Furthermore, 90 min of ischemic perfusion in saline or L-15 medium precipitated mitochondrial aberrations which resulted in further deterioration of de novo biosynthesis of APR plasma proteins. Regardless of the nature of the inflammatory stimuli, mitochondrial aberrations rendered the perfused organ a biologically inert tissue mass that was incapable of resuming biological function upon perfusion with oxygenated L-15 medium. This is most likely due to ischemia-induced irreversible hepatic necrosis. Thus, in vitro aberrations of mitochondrial function(s) critically limit the capability of the isolated liver to resume its organic function to sustain biosynthesis of de novo plasma proteins. Extrapolation of these results to the surgical management of end-stage liver diseases points to the importance of the status and the handling protocol(s) of the cadaver donor liver prior to successful grafting. We conclude that although histology of a cadaver liver may reveal well-preserved hepatic cellular organelles with at least minimal intra- and intercellular communication required for viable hepatic function, we deem it essential to further define acceptable minimal capabilities to de novo biosynthesize plasma proteins by a cadaver liver as a measure of its functional viability and suitability for transplantation. Ultimately, this measure may improve the success of liver transplants with minimal surgical and drug interventions.     

Neuropathology of the Central Nervous System in Acquired Immune Deficiency Syndrome (AIDS) in Japan

The neuropathologiesl features of the central nervous system in IS autopsy cases of Japanese male with AIDS were reported. Nine patients had various histological changes including a variety of opportunistic infections in six patients (40%), primary malignant lymphoma of the brain in two (13%), AIDS encephalopathy in four (27%) and vacuolar myelopathy in one (7%). Usually, these pathological changes were present concomitantly. AIDS encephalopathy was characterized by infiltration of mono and multinucleated cells and myelin pallor with astrogliosis located predominantly in the cerebral white matter and subcortical gray matter. Furthermore, unevenly distributed neuronal loss of the cerebral cortex was apparent in one case. Diffuse astrocytosis of the gray matter out of proportion to neuronal loss was also an outstanding finding in another case. The present study suggested that not only the white matter changes but also gray matter alterations might be the morphological substrates of AIDS encephalopathy.     

P300等诱发电位对亚临床肝性脑病早期诊断的意义

目的:观察事件相关电位P_(300)、体感诱发电位、视觉诱发电位和脑干听觉诱发电位在亚临床肝性脑病诊断中的意义。方法:50例亚临床肝性脑病患者进行了心理测验,并做了头颅CT和视觉诱发电位、体感诱发电位、脑干听觉诱发电位和事件相关电位检查,30例正常人做为对照组。结果:亚临床肝性脑病的心理测验,韦氏法智力低下率为76％,视觉诱发电位异常率为13％,脑干听觉诱发电位异常率为20％,体感诱发电位异常率为40％,事件相关电位异常率为71％,正常对照组四种诱发电位的正常率是100％。头颅CT结果与亚临床肝性脑病无关。结论:视觉诱发电位、体感诱发电位、脑干听觉诱发电位和事件相关电位在亚临床肝性脑病中是异常的。事件相关电位更为敏感,对亚临床肝性脑病的早期诊断有重要意义。     

OGD增加小鼠离体海马组织内cPKCβII和nPKCε的膜转位

目的:通过观察无糖低氧(OGD)刺激对小鼠海马脑片内蛋白激酶C(PKC)特定亚型膜转位水平(激活程度)的影响,进一步证实我们在整体低氧预适应小鼠模型上所获实验结果,并为离体海马脑片缺血/低氧预适应(I/HPC)模型建立及后续药物干预实验打下基础。方法:急性分离小鼠海马组织、制备400!μm厚度的脑片,并用无糖低氧(OGD)人工脑脊液(ACSF)模拟缺血/低氧刺激;应用SDS-PAGE和Westernbolt等生化技术,并结合GelDoc凝胶成像系统,半定量检测OGD刺激2、5、10、15和30min后海马脑片内cPKCβII和nPKCε的膜转位水平。结果:OGD刺激可增高海马脑片内cPKCβII和nPKCε的膜转位水平,且这种增高从刺激5min开始持续至30min均有显著差异(P<0.001,n=6)。结论:实验结果进一步证实cPKCβII和nPKCε可能参与脑缺血/低氧性预适应的形成过程,并提示OGD10min作为制备离体海马脑片I/HPC模型的预处理刺激较为合理。