The involvement of blood microvessels, representing the anatomic site of the blood-brain barrier (BBB), in brain damage induced by prenatal exposure to lipopolysaccharide (LPS) and/or valproic acid (VPA) was studied in four-week-old rats. The immunogold procedure was applied for localization at the ultrastructural level of endogenous albumin and glucose transporter (GLUT-1) in three brain regions: cerebral cortex, cerebellum and hippocampus. Four groups of rats were used: (1) untreated control, (2) prenatally VPA-treated, (3) prenatally LPS-treated, and (4) prenatally LPS- and VPA-treated. The functional state of the BBB was evaluated as follows: (a) by its tightness, i.e., permeability to blood-borne albumin, and (b) by the expression of GLUT-1 in the endothelial cells (ECs). Using morphometry, the labelling density for GLUT-1 was recorded over luminal and abluminal plasma membranes of the ECs, also providing information on their functional polarity. No extensive increase of vascular permeability and/or any considerable dysfunction of the BBB in experimental groups nos. 2 and 3 were observed, although in solitary vascular profiles, increased endocytosis or even transcytosis of albumin by ECs was noted. In experimental group no. 4, some vascular profiles showed scanty leakage (microleakage), manifested by the presence of immunosignals for albumin in the perivascular area. Although some fluctuations in the expression of GLUT-1 occurred in all experimental groups, especially in group no. 3, a most pronounced and significant diminution of the labelling density, in all three regions of the brain, was observed in group no. 4. This finding suggests the synergistic action of prenatally applied LPS and VPA that affects specific transport functions of glucose in the microvascular endothelium. The diminished or disturbed supply of glucose to selected brain regions can be one of the factors leading to previously observed behavioral disturbances in similarly treated rats.

Distribution of glucose transporter (GLUT-1) in brain microvascular endothelium, representing the anatomic site of the blood-brain barrier (BBB), was studied with electron microscopy in 24-month-old mice, which had been exposed prenatally (on 9th day of gestation) to a single teratogenic dose of ethanol. Offspring of mice that had received an equivalent volume of isocaloric dextrose served as controls. Sections of brain samples embedded at low temperature in hydrophilic resin Lowicryl K4M were exposed to anti-GLUT-1 antiserum followed by gold-labelled secondary antibodies. By using morphometry, the labelling density was recorded over luminal and abluminal plasma membranes of the endothelial cells of blood microvessels supplying four brain regions: cortex, hippocampus, cerebellum and olfactory bulb. We found that the density of immunosignals for GLUT-1, represented by colloidal gold particles, was unchanged in the olfactory bulb and slightly lowered in the abluminal plasmalemma of the vascular endothelium in the cerebral cortex of the ethanol-treated mice. In contrast, statistical analysis using Mann-Whitney U -test revealed that in the hippocampus and cerebellum, the density of immunolabelling of both plasma membranes of microvascular endothelial cells was significantly lowered in the ethanol-treated mice. These findings suggest that prenatally applied ethanol had a different influence on the vasculature supplying different brain regions. In effect, the inefficient supply of glucose to selected brain regions can be one of the factors leading to the previously observed deficit in long-term memory in a similar alcohol-treated group of mice.

The rat with micrencephaly, produced by prenatal exposure to methylazoxymethanol, provides a useful model to study neurobehavioral abnormalities associated with congenital brain defects. The micrencephalic animals have a life-long learning impairment. As they age, their already impaired learning competence deteriorates further. To determine whether the aging-associated functional deterioration could be ameliorated by a neural transplant, micrencephalic rats bearing solid transplants of normal fetal neocortical tissue since infancy were evaluated on a visual pattern discrimination learning at 15 months and a spatial navigation test at 24 months of age. The transplant-bearing rats learned both tasks significantly better than the micrencephalic rats without transplants. Morphometric analyses revealed that cortical pyramidal neurons were larger in the transplant-bearing rats than in micrencephalic rats without transplants. The life-long presence of a transplant appeared to have protected the micrencephalic brain against aging-associated deterioration. This is the first demonstration that a neural transplant, placed in a congenitally defective infant brain, can ameliorate aging-associated cognitive deficits.

Cytosol prepared from human placenta inhibits outwardly rectifying Cl- channels excised from HT29 cells. Size exclusion chromatography of cytosol on Superose 12 revealed two inhibitory fractions suggesting Cl- channel inhibitors of different size or molecular weight (MW). The ‘high MW’ inhibitor co-migrated with the proteins, whereas the ‘low MW inhibitor eluted together with tryptophan, xanthine, hypoxanthine, and nicotinamide. Although these substances did not inhibit Cl– channels we tentatively assume that the ‘low MW cytosolic inhibitor may be a heterocyclic aromatic compound. Alternatively, the ‘low MW inhibitor may be a steroid, because aldosterone has a similar retention time on Superose 12. We can as yet exclude a number of putative cytosolic Cl– channel inhibitors including glutathione, cAMP, cGMP, ATP, GTP, NADH, NADPH, and arachidonic acid.

As long as the question of which channels are responsible for cAMP-mediated epithelial Cl- secretion remains unsolved, it is still important to search for specific inhibitors that might help to relate macroscopic to microscopic events. Following the report by Sheppard and Welsh (J Gen Physiol 100: 573, 1992) that glibenclamide inhibits whole-cell Cl- currents in genetically manipulated fibroblasts expressing the cystic fibrosis transmembrane conductance regulator (CFTR), we have studied the effect of glibenclamide on different types of Cl- channels of HT29 and T84 cells at the single-channel level. Our results confirm that micromolar concentrations of glibenclamide inhibit the linear, low-conductance Cl-channel, which appears to represent CFTR and show that the inhibition results from a typical flicker block. However, the same concentrations of glibenclamide inhibit also the outwardly rectifying intermediate conductance Cl- channel which, potentially, may contribute to transepithelial Cl- secretion.

The compositional and structural stability of UHV-grown ultrathin cobalt films on Cu(111) are investigated by low-energy ion scattering. Even at room temperature migration of copper substrate atoms onto the cobalt film by surface diffusion occurs during and after the deposition process. The resulting film and interface structure therefore depends critically on deposition rate and temperature as well as on time of measurement. Our findings provide an explanation for the controversial results on structural and magnetic properties of Co/Cu films and multilayers.

The densities of neurofibrillary tangles (NFT) and neuritic plaques (NP) were assessed quantitatively in the brains of 303 mentally retarded adults 23 to 90 years of age at the time of their deaths (mean = 59.5 years). Cases with Down's syndrome, hydrocephalus and metabolic disorders were excluded from the study. Examinations of frontal, temporal, parietal, and occipital cortex, as well as hippocampus and parahippocampal gyrus were made in every case. NPs and/or NFTs were observed within the brains of 163 cases (53.8%). Detailed analyses indicated that NP density within all brain regions examined was positively related to age, with the largest age associated increases in density seen in frontal and temporal regions. In contrast, NFT density increased with age only within hippocampus and parahippocampal gyrus, but not neocortex. In addition, NP lesions within neocortex were more diffusely distributed across regions for older compared to younger cases, while no similar age-associated change in the topography of NFTs was observed. Finally, factor analyses of the combined NP and NFT data indicated that, while strong correlations existed across the various brain regions for measures of NP and NFT densities, considered separately, there was virtually no indication of regional associations between these two types of lesions. While these data, from cases with mental retardation, cannot be generalized directly to the nonretarded population, they provide strong evidence that models of Alzheimer pathogenesis must take into account the fact that regional densities of NPs and NFTs, and, therefore, the underlying processes associated with formation of these lesions, can be largely independent.

The rat with methylazoxymethanol-induced micrencephaly is a useful animal model of congenital brain defects and associated cognitive impairment. Born with profound morphological and neurochemical alterations in the forebrain, it shows impaired ability to learn mazes. In order to determine how an animal with such a developmentally damaged brain would function in old age, Long-Evans rats 6, 15, and 24 months of age were tested for their ability to learn to locate a hidden platform in the Morris water maze. The performance of micrencephalic rats of all ages was impaired on acquisition, retention, and transfer trials. Moreover, the magnitude of their acquisition deficit increased with age. It remains to be determined whether the premature decline of the micrencephalic rat in learning the task simply reflects a greater impact on an already compromised brain by neuron loss characteristic of aging brains or whether the prenatal insult alters some basic processes resulting in premature aging.

Journal Article Neuropathological Diagnostic Criteria For AD: a Reply to Lindenberg Get access H. M. Wisniewski, M.D., Ph.D., H. M. Wisniewski, M.D., Ph.D. Search for other works by this author on: Oxford Academic PubMed Google Scholar A. Rabe, Ph.D., A. Rabe, Ph.D. Search for other works by this author on: Oxford Academic PubMed Google Scholar W. Zigman, Ph.D., W. Zigman, Ph.D. Search for other works by this author on: Oxford Academic PubMed Google Scholar W. Silverman, Ph.D. W. Silverman, Ph.D. Search for other works by this author on: Oxford Academic PubMed Google Scholar Journal of Neuropathology & Experimental Neurology, Volume 49, Issue 5, September 1990, Page 537, https://doi.org/10.1097/00005072-199009000-00011 Published: 01 September 1990

This chapter discusses approach for discovering conditions under which normal fetal tissue transplanted into infant brains could ameliorate impaired function resulting from congenital brain defects. The approach is unique in 2 respects: (1) by adding new rather than replacing lost tissue, it improves the function of the host brain beyond its intrinsic capacity and (2) functional effects are assessed at maturity and in old age, even though transplants are sustained in infancy. The effect of transplants on some of the impaired behaviors is described in the chapter. In the approach described in the chapter, although the transplant was structurally well integrated into the host brain, its presence reduced neither the hyperactivity of micrencephalic rats in an open field nor the deficit they display in learning a multiple choice water maze. Both tests were done at 2 months and one year after transplantation. Electrophysiological recordings of electroencephalography and visual evoked potentials (VEP) obtained from young adult transplant-bearing micrencephalic rats have been more encouraging. Salutary transplant effects were also observed with two different behavioral tests given at older ages, a visual pattern discrimination test and spatial navigation.

AbstractA series of substituted nitrobenzenes such as (I), (III), (V), (VII) and (IX) is subjected to the reaction conditions A).

AbstractImmunology and biochemical studies of paired helical filaments (PHF) revealed the presence of the following proteins: (1) phosphorylated tau, (2) ubiquitin, and (3) neurofilament peptides. Quantitative biochemical studies of the PHF peptides are in progress, and as yet it is not known which of the above proteins or possibly, a novel protein is the initiator and major constitutent of PHF. The peptide‐forming amyloid fibers in the meninges, brain vessels, and neuritic plaques are a product of a host gene localized on chromosome 21. The reason for the formation of the amyloid fibers in normal aged people and in Alzheimer disease is unknown. However, in Down syndrome, it may be a result of a gene dose effect. Imbalance between the production of the amyloid fiber precursor protein and the ability to degrade it may also be the result of gene mutation of the amyloid peptide‐producing cell or a result of an enzyme defect or deficiency of the amyloidogenic peptide processor cells.

Annals of the New York Academy of SciencesVolume 495, Issue 1 p. 732-735 Transplants of Normal Fetal Cerebral Cortical Tissue into Congenitally Malformed Brains of Infant Rats M. H. LEE, M. H. LEE New York State Office of Mental Retardation and Developmental Disabilities Institute for Basic Research in Developmental Disabilities New York, New York 10314Search for more papers by this authorA. RABE, A. RABE New York State Office of Mental Retardation and Developmental Disabilities Institute for Basic Research in Developmental Disabilities New York, New York 10314Search for more papers by this authorJ. R. CURRIE, J. R. CURRIE New York State Office of Mental Retardation and Developmental Disabilities Institute for Basic Research in Developmental Disabilities New York, New York 10314Search for more papers by this authorJ. SHEK, J. SHEK New York State Office of Mental Retardation and Developmental Disabilities Institute for Basic Research in Developmental Disabilities New York, New York 10314Search for more papers by this authorH. M. WISNIEWSKI, H. M. WISNIEWSKI New York State Office of Mental Retardation and Developmental Disabilities Institute for Basic Research in Developmental Disabilities New York, New York 10314Search for more papers by this author M. H. LEE, M. H. LEE New York State Office of Mental Retardation and Developmental Disabilities Institute for Basic Research in Developmental Disabilities New York, New York 10314Search for more papers by this authorA. RABE, A. RABE New York State Office of Mental Retardation and Developmental Disabilities Institute for Basic Research in Developmental Disabilities New York, New York 10314Search for more papers by this authorJ. R. CURRIE, J. R. CURRIE New York State Office of Mental Retardation and Developmental Disabilities Institute for Basic Research in Developmental Disabilities New York, New York 10314Search for more papers by this authorJ. SHEK, J. SHEK New York State Office of Mental Retardation and Developmental Disabilities Institute for Basic Research in Developmental Disabilities New York, New York 10314Search for more papers by this authorH. M. WISNIEWSKI, H. M. WISNIEWSKI New York State Office of Mental Retardation and Developmental Disabilities Institute for Basic Research in Developmental Disabilities New York, New York 10314Search for more papers by this author First published: June 1987 https://doi.org/10.1111/j.1749-6632.1987.tb23725.xCitations: 1AboutPDF ToolsRequest permissionExport citationAdd to favoritesTrack citation ShareShare Give accessShare full text accessShare full-text accessPlease review our Terms and Conditions of Use and check box below to share full-text version of article.I have read and accept the Wiley Online Library Terms and Conditions of UseShareable LinkUse the link below to share a full-text version of this article with your friends and colleagues. Learn more.Copy URL Share a linkShare onEmailFacebookTwitterLinkedInRedditWechat References 1 Dambska, M., R. Haddad, P. B. Kozlowski, M. H. Lee & J. Shek 1982. Telencephalic cytoarchitectonics in the brains of rats with graded degrees of micrencephaly. Acta Neuropathol. (Berlin) 58: 203–209. 2 Yurkewicz, L., K. L. Valentino, M. K. Floeter, J. W. Fleshman, Jr. & E. G. Jones 1984. Effects of cytotoxic deletions of somatic sensory cortex in fetal rats. Somatosensory Res. 1: 303–327. 3 Johnston, M. V. & J. T. Coyle 1980. Ontogeny of neurochemical markers for noradrenergic, GABA-ergic, and cholinergic neurons in neocortex lesioned with methylazoxy-methanol acetate. J. Neurochem. 34: 1429–1441. 4 Rabe, A. & R. K. Haddad 1972. Methylazoxymethanol-induced micrencephaly in rats: Behavioral studies. Fed. Proc. 31: 1536–1539. 5 Vorhees, C. V., K. Fernandez, R. M. Dumas & R. K. Haddad 1984. Pervasive hyperactivity and long-term learning impairments in rats with induced micrencephaly from prenatal exposure to methylazoxymethanol. Dev. Brain Res. 15: 1–10. 6 Plonsky, M., E. P. Riley, M. H. Lee & R. K. Haddad 1985. The effects of prenatal methylazoxymethanol acetate (MAM) on holeboard exploration and shuttle avoidance performance in rats. Neurobehav. Toxicol. Teratol. 7: 221–226. 7 Das, G. D., B. H. Hallas & K. G. Das 1979. Transplantation of neural tissues in the brains of laboratory mammals: Technical details and comments. Experientia 35: 143–145. 8 Floeter, M. K. & E. J. Jones 1984. Connections made by transplants to the cerebral cortex of rat brains damaged in utero. J. Neurosci. 4: 141–150. Citing Literature Volume495, Issue1Cell and Tissue Transplantation into the Adult BrainJune 1987Pages 732-735 ReferencesRelatedInformation

Synthesis of Substituted N‐Hydroxylactams, Lactams, Quinoline‐N‐oxides, and Quinolines by Catalyzed Reductive Cyclization of 2‐Nitrocinnamoyl Derivatives with Hydrogen/Platinum BlackSubstituted nitrobenzenes 1a–1m, consisting of two series of 6 analogous compounds, containing the structural unit of an α,β‐substituted 2‐nitrocinnamoyl group have been reductively cyclized by means of hydrogen in the presence of platinum black catalyst to form four types of heterocycles: N‐hydroxylactams 2a and b, lactams 3 and 4, quinoline‐N‐oxides 5a–d, and quinolines 6a and b. The type of substituents at the 2‐nitrocinnamoyl group is of significance for the type of heterocycle formed in this reaction. It is of special interest that by the use of the reduction system hydrogen/platinum black the probability to obtain N‐hydroxylactams or quinoline‐N‐oxides, which are difficult to obtain by alternative procedures, becomes much higher than by the use of many reducing agents acting noncatalytically.