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Isolation and culture of cells derived from human cerebral microvessels 总被引:10,自引:0,他引:10
Harry V. Vinters Susan Reave Penny Costello John P. Girvin Steven A. Moore 《Cell and tissue research》1987,249(3):657-667
Summary Microvessels were isolated from non-neoplastic human cerebral cortical fragments resected for treatment of intractable seizure disorder. The microvessels were incubated in modified Lewis medium with 20 or 30% fetal bovine serum. Within 1–2 weeks, two cell populations emerged from the isolates. One type of cells had polygonal morphology, showed density-dependent contact inhibition at confluence in vitro, showed lectin-binding characteristics of endothelium (but only moderate positivity for factor VIII antigen), demonstrated induction of -glutamyl trans-peptidase when exposed to astrocyte-conditioned media, and responded to insulin by a pronounced increase in DNA synthesis. The other variety of cells grew in vitro more slowly in irregular strands separated by clear zones, showed ultrastructural features of smooth muscle, and isoelectric focusing of cell proteins revealed the presence of smooth-musclespecific -isoactin. Both types of cells could be serially subcultured. The ability to isolate and grow the two cell types, tentatively identified as human cerebral microvascular endothelium and smooth muscle, may facilitate studies of human blood-brain barrier function as well as the pathogenesis of cerebral microangiopathies unique to the human brain.Funded by Canadian Heart Foundation, Heart and Stroke Foundation of Ontario and UCLA Biomedical Research Support Grant 相似文献
3.
Thomas L. Pazdernik Matthew Layton Stanley R. Nelson Fred E. Samson 《Neurochemical research》1992,17(1):11-21
This overview presents data showing that glucose use increases and that excitatory amino acids (i.e., glutamate, aspartate), taurine and ascorbate increase in the extracellular fluid during seizures. During the cellular hyperactive state taurine appears to serve as an osmoregulator and ascorbate may serve as either an antioxidant or as a pro-oxidant. Finally, a unifying hypothesis is given for seizure-induced brain damage. This unifying hypothesis states that during seizures there is a release of excitatory amino acids which act on glutamatergic receptors, increasing neuronal activity and thereby increasing glucose use. This hyperactivity of cells causes an influx, of calcium (i.e. calcium stress) and water movements (i.e., osmotic stress) into the cells that culminate in brain damage mediated by reactive oxygen species.Special issue dedicated to Dr. Frederick E. Samson 相似文献
4.
Antipsychotics represent high affinity for sigma receptors and sigma-like drugs often have the psychotomimetic properties. Besides, the receptors are unevenly distributed in human brain. These findings suggest that sigma receptors might be involved in the pathophysiology of schizophrenia. Sigma receptors in rat and human brain were measured with [3H]-1, 3, di-o-tolylguanidine (DTG) and non-specific binding of [3H]DTG was determined in the presence of 10–5M haloperidol. Monovalent and divalent cations strongly inhibited [3H]DTG binding. Glutamate, aspartate and glycine also decreased the binding to human cerebral membranes. With post-mortem brain samples from 12 schizophrenics and 10 controls, sigma receptors were measured in 17 areas of cerebral cortex. Sigma receptors binding showed the regional differences in the cortex, but no significant differences between schizophrenics and controls were observed except the superior parietal cortex where the binding significantly increased in the schizophrenic group. These results suggest that sigma receptors in cerebral cortices might not be directly concerned with the pathophysiological role in schizophrenia.Dedicated to Dr. Morris Aprison. Received too late for publication in special issue. 相似文献
5.
Antoine M. Hakim Marie J. Arrieta Bernard A. Cooper† Hanna M. Pappius 《Journal of neurochemistry》1984,42(6):1582-1587
There is considerable debate on the role of folate in CNS function. Recent work indicates that folate deficiency may affect CNS serotonin metabolism, and clinical studies describe many consequences of such a deficiency. On the other hand some workers maintain that folate deficiency alone causes CNS abnormalities. We maintained rats, through dietary deprivation, at folate levels below 4 ng/ml for more than 6 weeks and showed that at that time both their liver and brain folate levels were significantly reduced. We then studied their local cerebral glucose utilization (LCGU) using the [14C]deoxyglucose technique. This method assesses cerebral function by measuring regional metabolic activity. We also determined LCGU in rats given the same diet but replenished with folate (folate control) and in others given free access to commercially available food (normal controls). Our results show that this degree of folate deficiency has no effect on cerebral function. This contrasts with the focal suppression of LCGU we previously reported in a model of vitamin B12 deficiency. 相似文献
6.
Raquel Fernández-Durango José A. de Juan Horatio Zimman Francisco J. Moya Mario Garcia de la Coba Arturo Fernández-Cruz 《Journal of neurochemistry》1994,62(4):1482-1488
Abstract: Specific endothelin (ET) binding sites were characterized in membranes prepared from human cerebral cortices using binding assay and cross-linking analysis. The presence of immunoreactive (IR) ET-1 was studied by radioimmunoassay. Saturation binding experiments revealed that the K D and B max for 125 I-ET-1 and 125 l-ET-3 to membranes from gray matter were 25 ± 6 pM and 115 ± 15 fmol/mg of protein and 24 ± 5 p M and 108 ± 13 fmol/mg of protein, respectively. Similar results were obtained for white matter. In the presence of 10 n M sarafotoxin-6c, which is selective for ETB receptors, 125 I-ET-1 and 125 l-ET-3 binding was totally abolished. However, in the presence of 1 μ M BQ123, which is selective for ETA receptors, both bindings were not affected. These results suggest that the human cerebral cortex contains only ETB receptors. Cross-linking of 125 I-ET-1 and 125 l-ET-3 to membranes with disuccinimidyl suberate resulted in the labeling of two bands of 48 and 31 kDa. Concentrations of IR-ET-1 in the gray and white matter were 7.0 ± 3.2 and 2.5 ± 1.7 fmol/g wet weight, respectively. The demonstration of high-affinity ETB receptors and the presence of IRET-1 suggest that the peptide may act as a neurotransmitter or neuromodulator in the human cerebral cortex. 相似文献
7.
通过对80例急性脑出血死亡组分析,发现死于脑疝的占62.5%,脑疝与一种或二种以上合并症同存者占77.5%,显著高于存活组(P<0.01).它们互为因果,加速死亡。因此,应重视早期或超早期采用简易定向锥颅脑内血肿碎吸术吸除血肿,同时注意维持生命体征稳定,加强脱水降颅压,预防、控制合并症等综合治疗。且要全面分析,相互兼顾,正确处置。这是帮助机体渡过调控障碍难关,挽救生命的有效治疗措施。 相似文献
8.
Stephen D. Bird Robert J. Walker Michael J. Hubbard 《In vitro cellular & developmental biology. Animal》1994,30(7):420-424
Summary The effect of a conventional antibiotic (penicillin/streptomycin) mixture on the widely used kidney epithelial cell line,
LLC-PK1, was investigated by measuring growth and intracellular free calcium. Free calcium concentration was the same in cells cultured
for 3 to 7 wk with (“plus”) and without (“minus”) antibiotics both at rest and when challenged with high (14 mM) external calcium. When exposed to vasopressin, minus cells exhibited significantly smaller calcium transients than plus
cells. A similar difference existed for transients elicited by a calcium ionophore, 4-br-A23187. After longer periods of culture
(>20 wk), minus cells grew slower than plus cells but on reaching confluence (minus cells took 1 day longer) the morphologies
and viabilities were indistinguishable. The finding that culture with penicillin/streptomycin reversibly modified some properties
of LLC-PK1 cells, at least partly through altered calcium homeostasis, is of importance for workers using this cell model to study drug
effects and raises the general possibility of similar effects on other cultured cells. 相似文献
9.
Trinidad Hernández-Caselles José Villalaín Juan C. Gómez-Fernández 《Molecular and cellular biochemistry》1993,121(2):119-126
The roles of sulfhydryl and disulfide groups in the specific binding of synthetic cannabinoid CP-55,940 to the cannabinoid receptor in membrane preparations from the rat cerebral cortex have been examined. Various sulfhydryl blocking reagents including p-chloromercuribenzoic acid (p-CMB), N-ethylmaleimide (NEM), o-iodosobenzoic acid (o-ISB), and methyl methanethiosulfonate (MMTS) inhibited the specific binding of [3H]CP-55,940 to the cannabinoid receptor in a dose-dependent manner. About 80–95% inhibition was obtained at a 0.1 mM concentration of these reagents. Scatchard analysis of saturation experiments indicates that most of these sulfhydryl modifying reagents reduce both the binding affinity (Kd) and capacity (Bmax). On the other hand, DL-dithiothreitol (DTT), a disulfide reducing agent, also irreversibly inhibited the specific binding of [3H]CP-55,940 to the receptor and about 50% inhibition was obtained at a 5 mM concentration. Furthermore, 5mM DTT was abelt to dissociate 50% of the bound ligand from the ligand-receptor complex. The marked inhibition of [3H]CP-55,940 binding by sulfhydryl reagents suggests that at least one free sulfhydryl group is essential to the binding of the ligand to the receptor. In addition, the inhibition of the binding by DTT implies that besides free sulfhydryl group(s), the integrity of a disulfide bridge is also important for [3H]CP-55,940 binding to the cannabinoid receptor. 相似文献
10.
Iron deficiency is a common micronutrient deficiency associated with metabolic changes in the levels of iron regulatory proteins, hepcidin and ferroportin. Studies have associated dysregulation of iron homeostasis to other secondary and life-threatening diseases including anaemia, neurodegeneration and metabolic diseases. Iron deficiency plays a critical role in epigenetic regulation by affecting the Fe2+/α-ketoglutarate-dependent demethylating enzymes, Ten Eleven Translocase 1–3 (TET 1–3) and Jumonji-C (JmjC) histone demethylase, which are involved in epigenetic erasure of the methylation marks on both DNA and histone tails, respectively. In this review, studies involving epigenetic effects of iron deficiency associated with dysregulation of TET 1–3 and JmjC histone demethylase enzyme activities on hepcidin/ferroportin axis are discussed. 相似文献