Teratogenic activity of methadone hydrochloride in mouse and chick embryos

Development ◽  
1973 ◽  
Vol 30 (2) ◽  
pp. 449-458
Author(s):  
A. Jurand

Teratogenic activity of methadone HCl (Physeptone, Burroughs Wellcome and Co.) was tested on inbred JBT/Jd and outbred Q strain mouse embryos and on chick embryos. 22–24 mg/kg injected subcutaneously on the 9th day of pregnancy caused by the 13th day exencephaly in 56 out of 479 JBT/Jd embryos but after 32 mg/kg only in 1 out of 220 of the Q strain. Some affected JBT/Jd embryos showed also rachischisis in the cervical area. The second abnormality shown by the embryos of both strains is Z-shaped kinkage of the spinal cord. In explanted chick embryos cultured in vitro as well as in embryos treated in ovo methadone causes non-closure of the neural tube with extensive necrosis of the neural plate cells in the cephalic region. The results of this study indicate that methadone, which is a neutropic drug, has an embryotoxic activity directed against the developing central nervous system.

Development ◽  
1995 ◽  
Vol 121 (5) ◽  
pp. 1301-1309 ◽  
Author(s):  
R. Tuttle ◽  
W.D. Matthew

Neurons can be categorized in terms of where their axons project: within the central nervous system, within the peripheral nervous system, or through both central and peripheral environments. Examples of these categories are cerebellar neurons, sympathetic neurons, and dorsal root ganglion (DRG) neurons, respectively. When explants containing one type of neuron were placed between cryosections of neonatal or adult sciatic nerve and neonatal spinal cord, the neurites exhibited a strong preference for the substrates that they would normally encounter in vivo: cerebellar neurites generally extended only on spinal cord, sympathetic neurites on sciatic nerve, and DRG neurites on both. Neurite growth from DRG neurons has been shown to be stimulated by neurotrophins. To determine whether neurotrophins might also affect the substrate preferences of neurites, DRG were placed between cryosections of neonatal spinal cord and adult sciatic nerve and cultured for 36 to 48 hours in the presence of various neurotrophins. While DRG cultured in NGF-containing media exhibited neurite growth over both spinal cord and sciatic nerve substrates, in the absence of neurotrophins DRG neurites were found almost exclusively on the CNS cryosection. To determine whether these neurotrophin-dependent neurite patterns resulted from the selective survival of subpopulations of DRG neurons with distinct neurite growth characteristics, a type of rescue experiment was performed: DRG cultured in neurotrophin-free medium were fed with NGF-containing medium after 36 hours in vitro and neurite growth examined 24 hours later; most DRG exhibited extensive neurite growth on both peripheral and central nervous system substrates.(ABSTRACT TRUNCATED AT 250 WORDS)


1992 ◽  
Vol 262 (4) ◽  
pp. R595-R603 ◽  
Author(s):  
Y. Xia ◽  
C. Jiang ◽  
G. G. Haddad

Using enzyme histochemistry and in vitro electrophysiological recordings in brain slices, we studied 1) the relative activity of cytochrome c oxidase (Cytox) and hexokinase (HK) and 2) cellular function by examining ionic homeostasis across cell membranes in the turtle and newborn (5 days old) and adult rat central nervous system. We found that Cytox was higher in the rostral than in the caudal brain regions of the adult rat and that the activity in the newborn is at least as high as in the adult rat. In contrast, adult turtles had very low Cytox activity throughout the central nervous system. Compared with that in the adult rat, HK activity in the newborn was generally lower in the rostral brain and cerebellum but similar or higher in the brain stem and spinal cord. In the turtle, HK activity was higher in the cerebellum, brain stem, and ventral horn of the spinal cord than in those in the rat. During anoxia, extracellular K+ increased by approximately 10-fold (from 3.2 to approximately 32 mM) in the adult brain stem but only by 2.6 mM in newborn rats. After glycolysis was blocked with iodoacetic acid (10-20 mM), extracellular K+ increased remarkably in both adult and newborn rats to approximately 35 mM. In contrast, the turtle brain tissue showed a slight and insignificant increase in extracellular K+ during complete anoxia or with iodoacetic acid; there was a modest increase in K+ when anoxia and iodoacetate were administered together. We conclude that 1) the newborn rat brain must rely either on higher glycolytic capacity or on a reduction of metabolic rate during O2 deprivation and 2) the turtle brain can subsist on nonglucose fuels or on fuels not requiring the citric acid cycle and the electron transfer chain.


Development ◽  
1997 ◽  
Vol 124 (16) ◽  
pp. 3025-3036 ◽  
Author(s):  
J. Fontaine-Perus ◽  
P. Halgand ◽  
Y. Cheraud ◽  
T. Rouaud ◽  
M.E. Velasco ◽  
...  

Chimeras were prepared by transplanting fragments of neural primordium from 8- to 8.5- and 9-day postcoital mouse embryos into 1.5- and 2-day-old chick embryos at different axial levels. Mouse neuroepithelial cells differentiated in ovo and organized to form the different cellular compartments normally constituting the central nervous system.The graft also entered into the development of the peripheral nervous system through migration of neural crest cells associated with mouse neuroepithelium. Depending on the graft level, mouse crest cells participated in the formation of various derivatives such as head components, sensory ganglia, orthosympathetic ganglionic chain, nerves and neuroendocrine glands. Tenascin knockout mice, which express lacZ instead of tenascin and show no tenascin production (Saga, Y., Yagi, J., Ikawa, Y., Sakakura, T. and Aizawa, S. (1992) Genes and Development 6, 1821–1838), were specifically used to label Schwann cells lining nerves derived from the implant. Although our experiments do not consider how mouse neural tube can participate in the mechanism required to maintain myogenesis in the host somites, they show that the grafted neural tube behaves in the same manner as the chick host neural tube. Together with our previous results on somite development (Fontaine-Perus, J., Jarno, V., Fournier Le Ray, C., Li, Z. and Paulin, D. (1995) Development 121, 1705–1718), this study shows that chick embryo constitutes a privileged environment, facilitating access to the developmental potentials of normal or defective mammalian cells. It allows the study of the histogenesis and precise timing of a known structure, as well as the implication of a given gene at all equivalent mammalian embryonic stages.


2008 ◽  
Vol 4 (1) ◽  
pp. 19-26 ◽  
Author(s):  
Xiaoqin Zhu ◽  
Robert A. Hill ◽  
Akiko Nishiyama

NG2 cells represent a unique glial cell population that is distributed widely throughout the developing and adult CNS and is distinct from astrocytes, mature oligodendrocytes and microglia. The ability of NG2 cells to differentiate into myelinating oligodendrocytes has been documented in vivo and in vitro. We reported recently that NG2 cells in the forebrain differentiate into myelinating oligodendrocytes but into a subpopulation of protoplasmic astrocytes (Zhu et al., 2008). However, the in vivo fate of NG2 cells in the spinal cord and cerebellum has remained unknown. To investigate the fate of NG2 cells in caudal central nervous system (CNS) regions in vivo, we examined the phenotype of cells that express EGFP in mice that are double transgenic for NG2CreBAC and the Cre reporter Z/EG. The fate of NG2 cells can be studied in these mice by permanent expression of EGFP in cells that have undergone Cre-mediated recombination in NG2 cells. We find that NG2 cells give rise to oligodendrocytes in both gray and white matter of the spinal cord and cerebellum, and to protoplasmic astrocytes in the gray matter of the spinal cord. However, NG2 cells do not give rise to astrocytes in the white matter of the spinal cord and cerebellum. These observations indicate that NG2 cells serve as precursor cells for oligodendrocytes and a subpopulation of protoplasmic astrocytes throughout the rostrocaudal axis of the CNS.


1989 ◽  
Vol 1 (3-4) ◽  
pp. 105-112 ◽  
Author(s):  
Terry W. Moody ◽  
Reina L. Getz ◽  
William J. Goldberg ◽  
Jerald J. Bernstein

Neuropeptide receptors were visualized in homografts of fetal cortex (E14) into adult rat cortex (immediate or 7 day delay) and spinal cord usingin vitroautoradiographic techniques to explore the expression of peptide receptors in the same graft tissue in different central nervous system implantation sites. Receptors for bombesin (BN)-like peptides developed in the grafts by 3 weeks postimplantation regardless of location or age of implantation pocket in host. After 4 weeks, the density of BN receptors was confined to the graft. In grafts to spinal cord, however, high densities of BN-like receptors were not confined to the graft but were distributed throughout the spinal cord. In contrast, the density of vasoactive intestinal polypeptide (VIP) and substance P (SP) receptors was moderate and low to undetectable in the fetal grafts. The development of the peptide receptors studied was graft donor tissue specific since they were not altered by central nervous system implantation site.


2021 ◽  
Vol 18 (1) ◽  
Author(s):  
Jan Spaas ◽  
Wouter M. A. Franssen ◽  
Charly Keytsman ◽  
Laura Blancquaert ◽  
Tim Vanmierlo ◽  
...  

Abstract Background Multiple sclerosis (MS) is a chronic autoimmune disease driven by sustained inflammation in the central nervous system. One of the pathological hallmarks of MS is extensive free radical production. However, the subsequent generation, potential pathological role, and detoxification of different lipid peroxidation-derived reactive carbonyl species during neuroinflammation are unclear, as are the therapeutic benefits of carbonyl quenchers. Here, we investigated the reactive carbonyl acrolein and (the therapeutic effect of) acrolein quenching by carnosine during neuroinflammation. Methods The abundance and localization of acrolein was investigated in inflammatory lesions of MS patients and experimental autoimmune encephalomyelitis (EAE) mice. In addition, we analysed carnosine levels and acrolein quenching by endogenous and exogenous carnosine in EAE. Finally, the therapeutic effect of exogenous carnosine was assessed in vivo (EAE) and in vitro (primary mouse microglia, macrophages, astrocytes). Results Acrolein was substantially increased in inflammatory lesions of MS patients and EAE mice. Levels of the dipeptide carnosine (β-alanyl-l-histidine), an endogenous carbonyl quencher particularly reactive towards acrolein, and the carnosine-acrolein adduct (carnosine-propanal) were ~ twofold lower within EAE spinal cord tissue. Oral carnosine treatment augmented spinal cord carnosine levels (up to > tenfold), increased carnosine-acrolein quenching, reduced acrolein-protein adduct formation, suppressed inflammatory activity, and alleviated clinical disease severity in EAE. In vivo and in vitro studies indicate that pro-inflammatory microglia/macrophages generate acrolein, which can be efficiently quenched by increasing carnosine availability, resulting in suppressed inflammatory activity. Other properties of carnosine (antioxidant, nitric oxide scavenging) may also contribute to the therapeutic effects. Conclusions Our results identify carbonyl (particularly acrolein) quenching by carnosine as a therapeutic strategy to counter inflammation and macromolecular damage in MS.


2018 ◽  
Vol 23 (1) ◽  
pp. 10-13
Author(s):  
James B. Talmage ◽  
Jay Blaisdell

Abstract Injuries that affect the central nervous system (CNS) can be catastrophic because they involve the brain or spinal cord, and determining the underlying clinical cause of impairment is essential in using the AMA Guides to the Evaluation of Permanent Impairment (AMA Guides), in part because the AMA Guides addresses neurological impairment in several chapters. Unlike the musculoskeletal chapters, Chapter 13, The Central and Peripheral Nervous System, does not use grades, grade modifiers, and a net adjustment formula; rather the chapter uses an approach that is similar to that in prior editions of the AMA Guides. The following steps can be used to perform a CNS rating: 1) evaluate all four major categories of cerebral impairment, and choose the one that is most severe; 2) rate the single most severe cerebral impairment of the four major categories; 3) rate all other impairments that are due to neurogenic problems; and 4) combine the rating of the single most severe category of cerebral impairment with the ratings of all other impairments. Because some neurological dysfunctions are rated elsewhere in the AMA Guides, Sixth Edition, the evaluator may consult Table 13-1 to verify the appropriate chapter to use.


1963 ◽  
Vol 44 (3) ◽  
pp. 475-480 ◽  
Author(s):  
R. Grinberg

ABSTRACT Radiologically thyroidectomized female Swiss mice were injected intraperitoneally with 131I-labeled thyroxine (T4*), and were studied at time intervals of 30 minutes and 4, 28, 48 and 72 hours after injection, 10 mice for each time interval. The organs of the central nervous system and the pituitary glands were chromatographed, and likewise serum from the same animal. The chromatographic studies revealed a compound with the same mobility as 131I-labeled triiodothyronine in the organs of the CNS and in the pituitary gland, but this compound was not present in the serum. In most of the chromatographic studies, the peaks for I, T4 and T3 coincided with those for the standards. In several instances, however, such an exact coincidence was lacking. A tentative explanation for the presence of T3* in the pituitary gland following the injection of T4* is a deiodinating system in the pituitary gland or else the capacity of the pituitary gland to concentrate T3* formed in other organs. The presence of T3* is apparently a characteristic of most of the CNS (brain, midbrain, medulla and spinal cord); but in the case of the optic nerve, the compound is not present under the conditions of this study.


1985 ◽  
Vol 55 ◽  
Author(s):  
F. Terry Hambrecht

ABSTRACTNeural prostheses which are commercially available include cochlear implants for treating certain forms of deafness and urinary bladder evacuation prostheses for individuals with spinal cord disorders. In the future we can anticipate improvements in bioelectrodes and biomaterials which should permit more sophisticated devices such as visual prostheses for the blind and auditory prostheses for the deaf based on microstimulation of the central nervous system.


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