Effects of MDL 72527, a Specific Inhibitor of Polyamine Oxidase, on Brain Edema, Ischemic Injury Volume, and Tissue Polyamine Levels in Rats After Temporary Middle Cerebral After Occlusion

Abstract The possible effects of the polyamine interconversion pathway on tissue polyamine levels, brain edema formation, and ischemic injury volume were studied by using a selective irreversible inhibitor, MDL 72527, of the interconversion pathway enzyme, polyamine oxidase. In an intraluminal suture occlusion model of middle coerebral artery in spontaneously hypertensive rats, 100 mg/kg MDL 72527 changed the brain edema formation from 85.7 ± 0.3 to 84.5 ± 0.9% in cortex ( P < 0.05) and from 79.9 ± 1.7 to 78.4 ± 2.0% in subcortex (difference not significant). Ischemic injury volume was reduced by 22% in the cortex ( P < 0.05) and 17% in the subcortex ( P < 0.05) after inhibition of polyamine oxidase by MDL 72527. There was an increase in tissue putrescine levels together with a decrease in spermine and spermidine levels at the ischemic site compared with the nonischemic site compared with the nonischemic site after ischemia-reperfusion injury. The increase in putrescine levels at the ischemic cortical and subcortical region was reduced by a mean of 45% with MDL 72527 treatment. These results suggest that the polyamine interconversion pathway has an important role in the postischemic increase ini putrescine levels and that blocking of this pathway can be neuroprotective against neuronal cell damage after temporary focal cerebral ischemia.     

Administration of anti-c-kit antibody into the cerebrospinal fluid leads to increased cell death in the developing cerebral cortex

It is generally believed that during development, neurons are usually produced in excess. Cell death occurs in the developing nervous system. The survival of the developing neurons depends on many factors derived from the target sites, of which the neuronal trophic factors are by far the best known. Stem cell factor (SCF) and its receptor, c-kit, is expressed in cells of nervous system during development and adulthood. Although the role of SCF/c-kit in the nervous system is so far not clear, in vitro studies indicate that SCF/c-kit is trophic to certain neurons derived from neural crest and cerebral cortex. In this study the effects of anti-c-kit antibody on cell death in the newborn chick cerebral cortex have been investigated. Injection of anti-c-kit antibody into the cisterna magnum increased the number of cell death and resulted in thinning of the cerebral cortex as compared to that from the control group. It is concluded that SCF/c-kit is essential for cortical progenitor cell survival in the cerebral cortex. Moreover, this method may be applied to the other factors and different CNS regions, allowing identification of factors involved in cell death. It additionally re-emphasizes the importance of further investigations into the potential roles of SCF/c-kit signaling in neurodegenerative diseases.     

吡拉西坦联合甘露醇对老年脑出血后脑水肿的疗效比较

目的:观察吡拉西坦联合甘露醇对老年脑出血后脑水肿患者颅内压、脑水肿体积、脑血肿体积及认知功能的影响。方法:104例脑出血后脑水肿老年患者随机分为观察组(54例)和对照组(50例)。对照组在常规治疗的基础上给予20%甘露醇注射液,观察组在对照组的基础上给予吡拉西坦注射液。治疗7天,观察两组颅内压、脑水肿体积、脑血肿体积及认知功能(分别采用MMSE、Mo CA评估)的变化。结果:治疗后,两组颅内压、脑水肿体积、脑血肿体积均明显下降而MMSE、Mo CA明显上升,且观察组各指标变化幅度均大于对照组,治疗后同期比较差异均有统计学意义(P0.05)。结论:吡拉西坦联合甘露醇治疗老年脑出血后脑水肿,控制颅内压、改善脑水肿与脑血肿,作用优于单用甘露醇,能更大程度保护认知功能。     

Expression of Neuronal Proteins in Cells from Normal Adult Rat Brain Propagated in Serial Culture

Abstract: Cells have been cultured from the brains of 60-day-old rats and propagated through 12 passages. The cells contain the high and middle, but not low, molecular weight neurofilament subunits and neuron-specific enolase, demonstrated by immunoblotting and immunocyto-chemistry with redundant antibodies. The cells did not have the morphology of neurons when cultured in medium containing fetal calf serum and growth factors. In low serum medium containing the same growth factors with the addition of dibutyryl cyclic AMP, the cells became smaller and developed long processes. Three clonal lines derived from these cultures had the same properties. These observations are in agreement with recent observations using mouse and human brain tissue and demonstrate that proteins normally associated with neurons can be found in dividing cells cultured from the brains of young adult rats.     

Epidermal Growth Factor in Synaptosomal Fractions of Mouse Cerebral Cortex

Using a specific and sensitive epidermal growth factor radioimmunoassay (EGF-RIA) we measured EGF concentrations in whole brain, cerebral cortex, and cerebral cortical synaptosomal (pinched-off presynaptic nerve terminals) fractions of 26-day-old mouse brain. The relative EGF concentration in synaptosomal fractions was significantly greater than the growth factor concentrations in whole brain or cerebral cortex. Intracerebral injection, in an amount of EGF, several-fold greater than whole brain EGF content, did not appreciably increase synaptosomal EGF concentration, suggesting that no artifact was involved. The high synaptosomal EGF content suggests a neurotransmitter or a neuromodulator role for EGF in the CNS.     

Etude cytochimique et ultrastructurale de l'évolution ovocytaire de Nereis pelagica L. (Annélide Polychète)

Résumé En l'absence d'hormone cérébrale, les ovocytes de N. pelagica subissent un accroissement rapide de taille. Ils présentent dans les grandes lignes une évolution cytologique parallèle à celle de l'ovogenèse naturelle. Ces ovocytes acquièrent en particulier des mucopolysaccharides acides qui se répartissent en fin d'évolution en une gangue corticale. Ce matériel toutefois est moins abondant que dans le cas de l'ovogenèse naturelle.A l'échelle de la microscopie électronique, diverses particularités caractérisent les ovocytes ayant évolué en condition anhormonale. Elles sont d'autant plus notables que le diamètre initial des ovocytes en expérimentation est plus faible. On note en particulier un accroissement des formations de reticulum et une augmentation considérable du nombre et de l'importance des lamelles annelées cytoplasmiques et intra-nucléaires. Enfin, la structure des lobules vitellins se caractérise par la présence de formations vésiculaires et lamellaires. La signification de ces modifications ultrastructurales est discutée.

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Cytochemical and ultrastructural study of oocyte development in Nereis pelagica L.II. Development in the absence of brain hormone

Summary In the absence of brain hormone, the oocytes of N. pelagica undergo a fast growth. They show a cytologic development parallel to that of natural oogenesis. In particular, these oocytes acquire acid mucopolysaccharides which finally form a cortical layer. However, this material is less abundant than in natural oogenesis.Electron microscopic investigation reveals some pecularities in oocytes growing under these abnormal conditions. The smaller the initial diameter of the oocytes, the more pronounced are these special traits. Most evident is an increase of the endoplasmic reticulum and a large augmentation in the number of cytoplasmic and intranuclear annulate lamellae. Moreover, the structure of the yolk bodies shows characteristic vesicular and membranous formations.The significance of these ultrastructural modifications is discussed.

     

Respiration in Primary Cultured Cerebellar Granule Neurons and Cerebral Cortical Neurons

Respiration was measured polarographically in primary cultures enriched with cerebellar granule neurons or cerebral cortical neurons. The basal respiratory rate, measured on the sixth day after culturing, was 12.00 natom equiv. O/mg protein/min for the cortical neurons and 12.70 natom equiv. O/mg protein/min for the granule neurons. Maximal stimulation by 2,4-dinitrophenol produced a 20-40% increase over the basal rate for both neuronal types. Oligomycin inhibited neuronal basal respiration by 45%. These respiratory rates in neurons from primary culture are markedly lower than those measured in astrocytes grown under similar conditions.     

Ultrastructural observations on human cerebral capillaries in organ culture

The use of an organotypic-in the strictly literal meaning of the word, nervous tissue culture device has allowed the identification and ultrastructural study of various types of developing capillaries in human cerebellum and olfactory bulb in vitro. Most capillaries were similar to those already described by other authors or by us, in human or animal embryos and fetuses. Large Type I Capillaries. Their luminal diameters were greater than 8 microns. The basement membranes were thin and discontinous. Numerous interendothelial junctions were either plate-like attachments or contained pentalaminar zones. Type II Capillaries. Their lumina were between 2 and 8 microns in diameter. The basement membranes were wider than those of type I capillaries and were sometimes continuous. The interendothelial junctional complexes of type II capillaries included pentalaminar portions. Many simple or complex vascular sprouts (type IV and V capillaries) had small or non-patent lumina. Their basement membranes were absent or very thin and discontinuous. Their interendothelial junctions were similar to those of type I capillaries. Some of the less frequently encountered capillary types seen in developing human nervous tissue were absent in culture. Some pathological features were seen-especially in long-term cultures-in type I and II capillaries containing degenerating blood cells or processes sometimes obviously related to histiocytic cells. They consisted mainly of an accumulation of microfilaments and modifications of the rough endoplasmic reticulum in the endothelial cells. These pathological changes did not modify the main characteristics of the capillaries. The origin of the vascular sprouts, the exact nature of the interendothelial junctions and the significance of the pathological changes are discussed. This model may prove useful for the study of cerebral vasculogenesis, the development of the blood-brain barrier and the physiological or pathological properties of the human brain capillaries in tissue culture.     

Oxidative Metabolism of Nonsynaptic Mitochondria Isolated from Rat Brain Hippocampus: A Comparative Regional Study

Nonsynaptic mitochondria isolated from rat brain hippocampus were compared with those obtained by means of the same preparative procedure from cerebral cortex and striatum. Protein recovery, marker enzyme activities (lactate dehydrogenase, citrate synthase, and acid phosphatase), state 4 respiration, and response to hypoosmotic shock showed no difference among the three cerebral regions, suggesting homogeneous behavior during the subfractionation procedure. Cholinergic markers--choline acetyltransferase, acetylcholinesterase activities, and high-affinity choline uptake--evaluated on synaptosomes showed the classic regional pattern with an enrichment in the striatum (striatum much greater than hippocampus). The coupling state of the mitochondrial fractions was maintained (respiratory control ratios ranging from 3.62 to 5.08 with glutamate + malate as oxidizable substrates), showing a metabolic competence sufficient to perform metabolic studies. Regional differences were found in state 3, uncoupled state of respiration, and cytochrome oxidase activity. Hippocampus showed the lower values (hippocampus less than striatum less than cortex). A possible role of this lower capacity of mitochondrial energy metabolism in determining the sensitivity of hippocampal neurons to ischemia or epileptic seizures is suggested.