Changes in alpha-fetoprotein and albumin synthesis rates and their levels during fetal and neonatal development of rat brain

An attempt was made to find a correlation between AFP and albumin levels in brain and their rates of synthesis in the brain cells during maturation of rat brain. Levels of alpha-fetoprotein (AFP) and albumin in the developing brain were studied by rocket immunoassay. Rate of synthesis of AFP and albumin in brain cell cultures, established from rat brain at various stages of development, were determined by incorporation of [14C]leucine into immuno-precipitable intracellular AFP and albumin. AFP and albumin levels in brain as well as rates of their synthesis by brain cells in culture registered a continuous decline during development. Synthesis of AFP and albumin in the brain is switched off after first week of postnatal life with a concomitant disappearance of these proteins from the brain. Levels of AFP and albumin in brain correlated well with rates of their synthesis by brain cells in vitro at any specific stage of brain maturation implying that levels of AFP and albumin in brain are regulated by controlling rates of their synthesis in the maturing brain cells.     

Rates of amino acid incorporation into particulate proteins in vivo and in slices of young and adult brain

Incorporation of a flooding dose of valine into brain proteins was measured in vivo and in brain slices, according to subcellular fraction and to solubility. In particulate fractions in vivo in the immature brain, soluble cytosol proteins had the highest synthesis rates (2.0% per hr), followed by microsomes (1.7%), mitochondria, nuclei (1.4%), and synaptosomes (0.85%). In adult, the rates were about half of those of immature animals except for microsomes, which were the same. In young, rates of incorporation into particles in brain slices were about 80% of in vivo rates, and adult rates were 10-20% of the in vivo rates. When brain proteins were fractionated into four groups--isotonic soluble, hypotonic soluble, Triton X-100 soluble, and the remainder solubilized in 0.2% SDS--in both young and adult brain in vivo, the isotonic fraction had the highest rate of protein synthesis, followed by the Triton-soluble fraction, the SDS-soluble fraction, and the hypotonic fraction. Also, with this method of separation in vitro rates for immature brain were 10-20% lower than in vivo rates, while in vitro adult rates were 80-90% lower. The results indicate that the most proteins are synthesized at a higher rate in the immature brain, and that the difference between in vivo and brain slice protein synthesis is not as great in the immature as in the mature brain in all the fractions examined.     

Determination of the origin and nature of brain macrophages and microglial cells in mouse central nervous system, using non-radioactive in situ hybridization and immunoperoxidase techniques.

The origin and nature of brain macrophages and microglial cells in the mouse central nervous system (CNS) were investigated. First, the expression and localization of determinants recognized by the different monoclonal antibodies (mAbs) MOMA-1, Mac-1-alpha, and F4/80 (raised against cells of the mononuclear phagocyte system) were immunohistochemically studied in the developing and adult mouse brain. In order to clarify the origin of brain macrophages and microglial cells, we used bacteriophage lambda transgenic mice as donors for bone marrow transplantations in recipient mice of different ages. During ontogeny, numerous MOMA-1-, Mac-1-alpha-, and F4/80-positive blood monocyte-derived brain macrophages (amoeboid microglia) infiltrated the CNS parenchyma. These brain macrophages gradually disappeared from the brain parenchyma at postnatal day 7 (P7). From P17 on, Mac-1-alpha- and F4/80-positive cells were detected within the brain parenchyma with the morphology of resting microglial cells. Transitional forms between brain macrophages and "resting" microglia were not observed in the developing brain. Combined non-radioactive in situ hybridization and immunohistochemistry revealed many MOMA-1-positive bone marrow-derived brain macrophages that were located in the leptomeninges, the ventricles, and occasionally the blood vessel walls. These results show that brain macrophages are of bone marrow origin. Many "resting" microglial cells were detected in the brain, mainly in the white matter. It appeared that about 10% of these cells displayed the transgenic signal. This result indicates that the majority of "resting" microglial cells are of local, presumably neuroectodermal, origin.     

小儿颅内肿瘤P-糖蛋白表达的定位检测及临床意义

目的 为了探讨小儿颅内肿瘤化疗失败的原因，本实验对２０例小儿颅内肿瘤Ｐ－糖蛋白的表达情况进行研究。方法 用单克隆抗体ＪＳＢ１及免疫组化法检测Ｐ－糖蛋白。结果 小儿颅内肿瘤Ｐ－糖蛋白表达很低，２０例中８例表达于血管内皮细胞，７例表达于纤维细胞，５例表达于浸润的淋巴细胞，肿瘤细胞只１例表达。结论 ８小儿颅内肿瘤化疗失败的原因是患儿血脑屏障Ｐ－糖蛋白表达，表现为对抗癌药物较强耐受而非肿瘤细胞表达Ｐ－糖蛋     

Steroid profiles in quail brain and serum: Sex and regional differences and effects of castration with steroid replacement

Both systemic and local production contribute to the concentration of steroids measured in the brain. This idea was originally based on rodent studies and was later extended to other species, including humans and birds. In quail, a widely used model in behavioural neuroendocrinology, it was demonstrated that all enzymes needed to produce sex steroids from cholesterol are expressed and active in the brain, although the actual concentrations of steroids produced were never investigated. We carried out a steroid profiling in multiple brain regions and serum of sexually mature male and female quail by gas chromatography coupled with mass spectrometry. The concentrations of some steroids (eg, corticosterone, progesterone and testosterone) were in equilibrium between the brain and periphery, whereas other steroids (eg, pregnenolone (PREG), 5α/β‐dihydroprogesterone and oestrogens) were more concentrated in the brain. In the brain regions investigated, PREG sulphate, progesterone and oestrogen concentrations were higher in the hypothalamus‐preoptic area. Progesterone and its metabolites were more concentrated in the female than the male brain, whereas testosterone, its metabolites and dehydroepiandrosterone were more concentrated in males, suggesting that sex steroids present in quail brain mainly depend on their specific steroidogenic pathways in the ovaries and testes. However, the results of castration experiments suggested that sex steroids could also be produced in the brain independently of the peripheral source. Treatment with testosterone or oestradiol restored the concentrations of most androgens or oestrogens, respectively, although penetration of oestradiol in the brain appeared to be more limited. These studies illustrate the complex interaction between local brain synthesis and the supply from the periphery for the steroids present in the brain that are either directly active or represent the substrate of centrally located enzymes.     

Drug and transmitter receptors in human brain. Characterization and localization of serotonin, dopamine and adrenergic receptors

The neuroreceptors in the brain are the targets of transmitters and drugs. Tritiated ligands - mostly selective antagonists - allowed to characterize the dopamine, serotonin and adrenergic receptors in human brain. Their properties were compared to those of rat brain receptors. Our results confirm the high affinity of several antagonist drugs for the corresponding binding sites in human brain. D2 dopamine receptors were identified in the striatum. S2 serotonergic receptors were located mainly in the cerebral cortex and their binding properties in solubilized form did not differ from those of the rat brain solubilized receptors. Adrenergic receptors were located either in cortical and subcortical areas. The subregional study indicates that wide variations could occur between adjacent areas of the cortex and between the different cortical layers. The subcellular distribution of several receptors revealed a main synaptosomal localization in human brain in contrast to other species. The S2 serotonergic receptors, the substance P peptide receptors and the benzodiazepine receptors were studied in the brain of Parkinsonian patients. The results were compared with those obtained in other neurological illnesses. A decrease in receptor number often corresponds to neuronal cell loss in degenerative diseases.     

Expression of long-patch and short-patch DNA mismatch repair proteins in the embryonic and adult mammalian brain

Expression of the DNA mismatch repair (MMR) pathway was examined in the adult and developing rat brain. Rat homologues of human GTBP and MSH2, which are essential components of the post-replicative DNA MMR system, were identified in nuclear extracts from the adult and developing rat brain. Developmental studies showed that both GTBP and MSH2 levels were higher in nuclei isolated from the embryonic brain (day 16) than adult brain. However, this difference was not as dramatic as the difference in the number of proliferating cells. Levels of thymine DNA glycosylase (TDG), the enzyme which catalyzes the first step in short patch G:T mismatch repair, were also decreased in adult compared to embryonic brain. In the adult brain, MMR proteins were elevated in nuclear extracts enriched for neuronal nuclei. These results suggest that adult brain cells have the capacity to carry out DNA mismatch repair, in spite of a lack of ongoing DNA replication.     

颅脑损伤后血清TNF-α和IL-10的含量变化及意义

目的 探讨急性颅脑损伤后血清肿瘤坏死因子α（TNF-α）和白细胞介素10（IL-10）的含量变化及临床意义。方法 采用双抗体夹心ABC-ELISA方法,检测60例急性颅脑损伤患者伤后血清TNF-α和IL-10含量的变化。结果 TNF-α、IL-10在伤后早期即明显升高,并与伤情轻重呈正相关。结论 TNF-α和IL-10参与了急性颅脑损伤后的炎性反应过程,血清中TNF-α和IL-10含量在颅脑损伤后明显升高,与颅脑损伤程度呈正相关,并可能在继发性脑损害中起重要作用。     

Localization and characterization of phenylethanolamine N-methyl transferase in the brain of various mammalian species.

The distribution of PNMT activity in various regions and nuclei of the rat, monkey and human brain was investigated. The distribution of PNMT activity in the rat brain correlates with the distribution of PNMT immunofluorescence. The PNMT activity in the primate brain is more widely distributed than in the rat brain. High and intermediate enzyme activity values were dound in the same regions of the primate brain as in the rat brain. Intermediate or low levels were also found in various other regions of the primate brain, e.g., basal ganglia, amygdala, septum, habenula. The brain PNMT has the same substrate specificity and similar kinetic properties as the adrenal enzyme. Immunotitration studies revealed cross-reactivity between the homologous adrenal and brain PNMT.     

重型颅脑损伤CT表现与预后关系分析

目的 介绍重型颅脑损伤CT分型方法,探讨其判断病情和预后的价值。方法 回顾208例重型颅脑损伤CT表现及相关临床资料,分析不同类型CT表现与病情和预后的关系。结果 本组病例在应用CT分型后CT显示的各型脑损伤部位、范围、轻重程度等对患者预后有显著影响。结论 CT分型具有早期判断重型颅脑损伤病情及预后的价值     

Corticosterone and dehydroepiandrosterone in songbird plasma and brain: effects of season and acute stress

Prolonged increases in plasma glucocorticoids can exacerbate neurodegeneration. In rats, these neurodegenerative effects can be reduced by dehydroepiandrosterone (DHEA), an androgen precursor with anti-glucocorticoid actions. In song sparrows, season and acute restraint stress affect circulating levels of corticosterone and DHEA, and the effects of stress differ in plasma collected from the brachial and jugular veins. Jugular plasma is an indirect index of the neural steroidal milieu. Here, we directly measured corticosterone and DHEA in several brain regions and jugular plasma, and examined the effects of season and acute restraint stress (30 min) ( n  = 571 samples). Corticosterone levels were up to 10× lower in brain than in jugular plasma. In contrast, DHEA levels were up to 5× higher in brain than in jugular plasma and were highest in the hippocampus. Corticosterone and DHEA concentrations were strongly seasonally regulated in plasma but, surprisingly, not seasonally regulated in brain. Acute stress increased corticosterone levels in plasma and brain, except during the molt, when stress unexpectedly decreased corticosterone levels in the hippocampus. Acute stress increased DHEA levels in plasma during the molt but had no effects on DHEA levels in brain. This is the first study to measure (i) corticosterone or DHEA levels in the brain of adult songbirds and (ii) seasonal changes in corticosterone or DHEA levels in the brain of any species. These results highlight several critical differences between systemic and local steroid concentrations and the difficulty of using circulating steroid levels to infer local steroid levels within the brain.     

血红蛋白和血红素氧合酶抑制剂在脑出血迟发性脑水肿中的作用

目的 研究血红蛋白(Hb)与脑出血迟发性脑水肿的关系,锌原卟啉(ZnPP)在脑出血迟发性脑水肿中的作用,为治疗脑出血迟发性脑水肿提供新的方法.方法 将大鼠分为生理盐水组、血红蛋白组和ZnPP组,向大鼠的尾状核分别注入生理盐水(NS组)和自体Hb溶液(Hb组和ZnPP组),并向ZnPP组大鼠腹腔内注射ZnPP,观察各组血脑屏障(BBB)通透性的变化、Hb的分解情况、脑水肿的程度和脑组织病理表现.结果 与Hb组大鼠相比,ZnPP组大鼠BBB通透性降低、Hb的分解产物减少和脑含水量降低(P<0.05).结论 Hb可以引起脑水肿,ZnPP对脑出血迟发性脑水肿有治疗作用.     

MMP-2及PTEN在人脑星形细胞瘤中的表达及意义

目的探讨基质金属蛋白酶2(MMP-2)及抑癌基因PTEN在人脑星形瘤中的表达及二者与人脑星形细胞瘤侵袭性的关系。方法用免疫组织化学SABC法检测50例人脑星形细胞瘤组织和10例正常人脑组织中的MMP-2和PTEN蛋白的表达,并且分析二者与人脑星形细胞瘤临床病理分级的关系。结果 MMP-2和PTEN在低度恶性星形细胞瘤和高度恶性星形细胞瘤组织中表达差别有统计学意义(p<0.05)。随着星形细胞瘤恶性度增高,MMP-2的表达强度呈上升趋势而PTEN表达强度逐渐下降;Spearman等级相关分析表明人脑星形细胞瘤中MMP-2和PTEN之间呈负相关(Rs=-0.518,P<0.01)。结论 MMP-2和PTEN是人脑星形细胞瘤分化程度和转移的潜在生物学指标,联合检测MMP-2和PTEN更有利于判断星形细胞瘤生物学行为和病理分级。     

Brain and blood microRNA expression profiling of ischemic stroke, intracerebral hemorrhage, and kainate seizures

MicroRNAs (miRNAs) regulate gene expression and have a critical role in many biologic and pathologic processes. We hypothesized that miRNA expression profiles in injured brain (hippocampus) would show common as well as unique profiles when compared with those of blood. Adult, untouched, control rats were compared with rats with sham surgeries, ischemic strokes, brain hemorrhage (lysed blood, fresh blood, or thrombin), and kainate-induced seizures. Brain and whole-blood miRNA expression profiles were assessed 24 h later using TaqMan rodent miRNA arrays. MicroRNA response profiles were different for each condition. Many miRNAs changed more than 1.5-fold in brain and blood after each experimental manipulation, and several miRNAs were upregulated or downregulated in both brain and blood after a given injury. A few miRNAs (e.g., miR-298, miR-155, and miR-362-3p) were upregulated or downregulated more than twofold in both brain and blood after several different injuries. The results show the possible use of blood miRNAs as biomarkers for brain injury; that selected blood miRNAs may correlate with miRNA changes in the brain; and that many of the mRNAs, previously shown to be regulated in brain and blood after brain injury, are likely accounted for by changes in miRNA expression.     

重度脑创伤后脑组织氧代谢变化及细胞凋亡与预后关系

目的 :探讨重度脑创伤后脑组织氧代谢变化及细胞凋亡与预后的关系。方法 :动态监测重度脑创伤患者脑组织氧分压、二氧化碳分压、pH值及脑温变化 ,检测脑挫伤灶周围组织细胞凋亡率。分析以上指标变化与预后的关系。结果 :与对照组比较 ,伤后脑组织氧分压和pH值下降 (P <0 0 5 ) ,二氧化碳分压及脑温升高 (P <0 0 5 ) ,脑挫伤灶周围组织存在细胞凋亡 ,以上指标变化与患者预后有关。结论 :重度脑创伤后脑组织氧代谢紊乱及细胞凋亡是影响脑创伤患者预后的重要因素     

Traumatic brain injury and schizophrenia in members of schizophrenia and bipolar disorder pedigrees

OBJECTIVE: Schizophrenia following a traumatic brain injury could be a phenocopy of genetic schizophrenia or the consequence of a gene-environment interaction. Alternatively, traumatic brain injury and schizophrenia could be spuriously associated if those who are predisposed to develop schizophrenia have greater amounts of trauma for other reasons. The authors investigated the relationship between traumatic brain injury and psychiatric diagnoses in a large group of subjects from families with at least two biologically related first-degree relatives with schizophrenia, schizoaffective disorder, or bipolar disorder. METHOD: The Diagnostic Interview for Genetic Studies was used to determine history of traumatic brain injury and diagnosis for 1,275 members of multiplex bipolar disorder pedigrees and 565 members of multiplex schizophrenia pedigrees. RESULTS: Rates of traumatic brain injury were significantly higher for those with a diagnosis of schizophrenia, bipolar disorder, and depression than for those with no mental illness. However, multivariate analysis of within-pedigree data showed that mental illness was related to traumatic brain injury only in the schizophrenia pedigrees. Independent of diagnoses, family members of those with schizophrenia were more likely to have had traumatic brain injury than were members of the bipolar disorder pedigrees. The members of the schizophrenia pedigrees also failed to show the gender difference for traumatic brain injury (more common in men than in women) that was expected and was present in the bipolar disorder pedigrees. Subjects with a schizophrenia diagnosis who were members of the bipolar disorder pedigrees (and thus had less genetic vulnerability to schizophrenia) were less likely to have had traumatic brain injury (4.5%) than were subjects with schizophrenia who were members of the schizophrenia pedigrees (and who had greater genetic vulnerability to schizophrenia) (19.6%). CONCLUSIONS: Members of the schizophrenia pedigrees, even those without a schizophrenia diagnosis, had greater exposure to traumatic brain injury compared to members of the bipolar disorder pedigrees. Within the schizophrenia pedigrees, traumatic brain injury was associated with a greater risk of schizophrenia, consistent with synergistic effects between genetic vulnerability for schizophrenia and traumatic brain injury. Posttraumatic-brain-injury schizophrenia in multiplex schizophrenia pedigrees does not appear to be a phenocopy of the genetic disorder.     

颅脑损伤程度对大鼠脑血流及氧代谢的影响

目的 对颅脑损伤影响脑血流及氧代谢进行前瞻性研究。方法 30只Wistar大白鼠分成3组：颅脑损伤1组（TBI1）、2组（TBI2）及3组（TBI3）各10只，分别为轻、中、重型颅脑损伤。用脑阻抗（REG）测定脑血流量，颈内静脉血氧饱和度（SjVO2)反映全脑氧代谢情况。结果 TBI、TBI2及TBI3组影响脑血流和氧代谢程度依次为TBI3＞TBI2＞TBI1，健侧脑组织含水量各组无明显差异，伤侧脑组织含水量TBI3组最多，其次为TBI2，明显高于TBI1组（P＜0．01）。结论 颅脑损伤后脑血流和氧代谢变化取决于损伤程度，脑血流和氧代谢各参数的监测对正确认识脑组织病理生理变化，指导临床治疗，判断预后有重要价值。     

Comparative effects of postnatal undernutrition and methadone exposure on protein and nucleic acid contents of the brain and cerebellum in rats

The neurochemical effect of postnatal exposure to methadone (METH), undernutrition (UND), and methadone and undernutrition (METH-UND) on the whole brain and cerebellum were examined in 21- and 60-day-old rats. At 21 days, body weight reductions of UND and METH-UND rats exceeded that of the METH animals. However, METH rats had the most severe deficits in the weight and total DNA content of the brain and cerebellum, as well as in brain DNA concentration. All experimental rats were subnormal in body weight at 60 days, as was the brain weight of METH-UND rats. Total brain DNA content was most reduced in 60-day-old METH animals, whereas brain RNA content and cerebellar DNA content was only lower in UND and METH-UND animals. These results suggest that methadone often has a greater retarding effect on whole brain and cerebellar development than would be expected by reduced caloric intake alone, and that at least part of the growth inhibiting effects of this drug originates from nonnutritional causes.     

烟雾病的MRI和MRA诊断

目的探讨磁共振成像(MRI)和磁共振动脉成像(MRA)对烟雾病的诊断价值。方法回顾性分析22例烟雾病患者的临床和影像资料,全部行MRI和MRA(3D-TOF法)检查,其中10例进行了DSA检查。结果MRI上脑实质内均出现异常信号,其中脑梗死8例,脑出血7例,脑萎缩3例,脑软化4例,8例患者在基底节区有血管流空现象。MRA均良好显示病变血管狭窄或闭塞,呈多支受累,与DSA所见相似。结论MRI结合MRA是诊断烟雾病的无创和有效手段。     

Regional distribution of glutamate and aspartate in adult and old human brain

In previous studies on rat brain we found that the observed heterogeneity of the regional distribution of amino acids was much greater when small well-defined anatomical structures were assayed. We therefore reinvestigated the distribution of glutamate and aspartate in 50 discrete areas from adult and old human brain. The concentration of glutamate in the area of highest level was 4.5 and 4.7 times as high as in the area of lowest level in adult and old brain respectively; for aspartate these values were 3.0 and 6.6. Several changes in old brain were noted. The human pattern differed from that in rat.