Regional Distribution of Angiotensinogen in the Central Nervous System of the Rat: Effect of DOC-Salt Treatment

1982 ◽  
Vol 63 (s8) ◽  
pp. 149s-152s ◽  
Author(s):  
Nidia Basso ◽  
Diana Grispon ◽  
Patricia Ruiz ◽  
Alberto C. Taquini

1. The distribution of angiotensinogen and endogenous renin-like activity were analysed in different areas of the central nervous system in normal and DOC-salt-treated hypertensive rats. 2. Angiotensinogen concentration and renin-like activity were significantly increased in the cerebral cortex, cerebellum, hypothalamus and brain stem of the DOC-salt-treated rats 30 days after the initiation of the experiment. 3. Influence of plasma contamination on the former results was evaluated by the determination of (a) plasma angiotensinogen concentration in control and treated animals and (b) blood content remaining in the different regions of the central nervous system, after saline perfusion of the brain, in a group of normal rats. 4. Plasma angiotensinogen concentration was significantly decreased in DOC-salt-treated rats, therefore blood contamination would tend to diminish the magnitude of increase in central nervous system angiotensinogen in these animals. 5. Present results have shown an increased concentration of angiotensinogen in some areas of the central nervous system in DOC-salt-treated rats. The results have also confirmed an enhanced activity of the endogenous renin-like enzyme in the same regions; this change seems to be mainly due to the increment in angiotensinogen. Increased formation of central angiotensin could be involved in the development of DOC-salt hypertension. The biosynthetic pathways of renin substrate as well as its endogenous regulation remain undetermined.

Hypertension ◽  
2012 ◽  
Vol 60 (suppl_1) ◽  
Author(s):  
Srinivas Sriramula ◽  
Huijing Xia ◽  
Eric Lazartigues

Elevated reactive oxygen species (ROS) in the central nervous system (CNS) through NADPH oxidase and diminished Nitric oxide (NO) levels are involved in the pathogenesis of hypertension. We previously reported that central Angiotensin Converting Enzyme 2 (ACE2) overexpression prevents the development of hypertension induced by DOCA-salt in a transgenic mouse model (syn-hACE2; SA) with human ACE2 targeted selectively to neurons in the CNS. While baseline blood pressure (BP; telemetry) was not different among genotypes, DOCA-salt treatment (1mg/g body wt DOCA, 1% saline in drinking water for 3 weeks) resulted in significantly lower BP level in SA mice (122 ±3 mmHg, n=12) compared to non-transgenic (NT) littermates (138 ±3 mmHg, n=8). To elucidate the mechanisms involved in this response, we investigated the paraventricular nucleus (PVN) expression of Nox-2 (catalytic subunit of NADPH oxidase), 3-nitrotyrosine, and endothelial nitric oxide synthase (eNOS) and anti-oxidant enzymes superoxide dismutase (SOD) and catalase in the hypothalamus. DOCA-salt treatment resulted in decreased catalase (95.2 ±5.6 vs. 113.8 ±17.6 mmol/min/ml, p<0.05) and SOD (4.1 ±0.4 vs. 5.9 ±0.2 U/ml, p<0.01) activities in hypothalamic homogenates of NT mice, which was prevented by ACE2 overexpression (141.8 ±9.9 vs. 142.1 ±9.2 mmol/min/ml and 5.9 ±0.3 vs. 7.9 ±0.2 U/ml, respectively). NT mice treated with DOCA-salt showed increased oxidative stress as indicated by increased expression of Nox-2 (61 ±5 % increase, n=9, p<0.001 vs. NT) and 3-nitrotyrosine (89 ±32 % increase, n=9, p<0.01 vs. NT) in the PVN which was attenuated in SA mice. Furthermore, DOCA-salt hypertension resulted in decreased phosphorylation of eNOS-ser1177 in the PVN (33 ±5 % decrease, n=9, p<0.05 vs NT) and this decrease was prevented by ACE2 overexpression. Taken together, these data provide evidence that brain ACE2 regulates the balance between NO and ROS levels, thereby preventing the development of DOCA-salt hypertension.


1947 ◽  
Vol 24 (1-2) ◽  
pp. 145-183 ◽  
Author(s):  
P. D. NIEUWKOOP

1. With the aseptic operation method of Woerdeman (1930) it is possible to rear duplicitas larvae, formed after grafting of the dorsal blastoporal lip in the place of the ventral one at the early gastrula stage (Spemann, 1918), till an age of about 4 weeks, a time at which they have completely consumed their yolk material. 2. Various forces acting in the normal development and in the development of the duplicitas larvae are discussed in connexion with the external form and the internal organization of the latter. 3. The sources of errors in the method of graphic reconstruction of the brain used in this investigation are checked and their elimination is discussed. 4. The structure of the duplicitas shows that there exists a mediolateral and probably also a cranio-caudal regulation in grafts of the dorsal blastoporal lip of the early gastrula. 5. In the brain one may distinguish between ‘primary’ structures which are always present, and ‘secondary’ structures which are more variable. Therefore, one may probably divide the causal analysis of the development of the central nervous system into the determination of the ‘ground plan’ of the primary structures and the more dependent development of the ‘secondary’ ones (specific formations). 6. The brains of the secondary embryonic rudiments of these duplicitas are formed in all cases up to a certain level; caudally to this level the brain-parts are normally proportioned, but the most anterior part may be reduced in size. This material can be arranged into a complete regression series, beginning with the reduction of the telencephalon and ending with a completely acephalic embryo. From this development one may conclude that the determination of the central nervous system occurs in a large number of successive zones, which are qualitatively ‘equivalent’, and which are determined by (qualitatively or quantitatively) different values of the organizing ‘agent’. 7. There are indications that the infundibulum and hypophysis are determined by a triple contact between presumptive neural plate, prechordal plate and cephalic ectoderm after the appearance of the neural plate. 8. After special staining these incomplete nervous systems may form a very important source of data for the causal analysis of the development of tracts and nuclei in the central nervous system. 9. With the conclusions drawn from these experiments and the data given in the extensive literature on this subject, a new working hypothesis on the determination of the central nervous system is put forward. This theory involves the assumption (among others) of an equilibrium reaction between a strong mesodermal and a weak ectodermal gradient. The character of the determination process probably changes from being at first purely quantitative to become qualitative with increasing age. 10. Finally, the regional determination of the secondary rudiment in duplicitas is probably determined by a triple interaction between the induction field of the graft, the primary regional structure of the ectoderm and the regional influences of the primary rudiment.


Author(s):  
S.S. Spicer ◽  
B.A. Schulte

Generation of monoclonal antibodies (MAbs) against tissue antigens has yielded several (VC1.1, HNK- 1, L2, 4F4 and anti-leu 7) which recognize the unique sugar epitope, glucuronyl 3-sulfate (Glc A3- SO4). In the central nervous system, these MAbs have demonstrated Glc A3-SO4 at the surface of neurons in the cerebral cortex, the cerebellum, the retina and other widespread regions of the brain.Here we describe the distribution of Glc A3-SO4 in the peripheral nervous system as determined by immunostaining with a MAb (VC 1.1) developed against antigen in the cat visual cortex. Outside the central nervous system, immunoreactivity was observed only in peripheral terminals of selected sensory nerves conducting transduction signals for touch, hearing, balance and taste. On the glassy membrane of the sinus hair in murine nasal skin, just deep to the ringwurt, VC 1.1 delineated an intensely stained, plaque-like area (Fig. 1). This previously unrecognized structure of the nasal vibrissae presumably serves as a tactile end organ and to our knowledge is not demonstrable by means other than its selective immunopositivity with VC1.1 and its appearance as a densely fibrillar area in H&E stained sections.


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.


2018 ◽  
Vol 25 (28) ◽  
pp. 3333-3352 ◽  
Author(s):  
Natalia Pessoa Rocha ◽  
Ana Cristina Simoes e Silva ◽  
Thiago Ruiz Rodrigues Prestes ◽  
Victor Feracin ◽  
Caroline Amaral Machado ◽  
...  

Background: The Renin-Angiotensin System (RAS) is a key regulator of cardiovascular and renal homeostasis, but also plays important roles in mediating physiological functions in the central nervous system (CNS). The effects of the RAS were classically described as mediated by angiotensin (Ang) II via angiotensin type 1 (AT1) receptors. However, another arm of the RAS formed by the angiotensin converting enzyme 2 (ACE2), Ang-(1-7) and the Mas receptor has been a matter of investigation due to its important physiological roles, usually counterbalancing the classical effects exerted by Ang II. Objective: We aim to provide an overview of effects elicited by the RAS, especially Ang-(1-7), in the brain. We also aim to discuss the therapeutic potential for neuropsychiatric disorders for the modulation of RAS. Method: We carried out an extensive literature search in PubMed central. Results: Within the brain, Ang-(1-7) contributes to the regulation of blood pressure by acting at regions that control cardiovascular functions. In contrast with Ang II, Ang-(1-7) improves baroreflex sensitivity and plays an inhibitory role in hypothalamic noradrenergic neurotransmission. Ang-(1-7) not only exerts effects related to blood pressure regulation, but also acts as a neuroprotective component of the RAS, for instance, by reducing cerebral infarct size, inflammation, oxidative stress and neuronal apoptosis. Conclusion: Pre-clinical evidence supports a relevant role for ACE2/Ang-(1-7)/Mas receptor axis in several neuropsychiatric conditions, including stress-related and mood disorders, cerebrovascular ischemic and hemorrhagic lesions and neurodegenerative diseases. However, very few data are available regarding the ACE2/Ang-(1-7)/Mas receptor axis in human CNS.


Author(s):  
Asfree Gwanyanya ◽  
Christie Nicole Godsmark ◽  
Roisin Kelly-Laubscher

Abstract: Ethanolamine is a bioactive molecule found in several cells, including those in the central nervous system (CNS). In the brain, ethanolamine and ethanolamine-related molecules have emerged as prodrug moieties that can promote drug movement across the blood-brain barrier. This improvement in the ability to target drugs to the brain may also mean that in the process ethanolamine concentrations in the brain are increased enough for ethanolamine to exert its own neurological ac-tions. Ethanolamine and its associated products have various positive functions ranging from cell signaling to molecular storage, and alterations in their levels have been linked to neurodegenerative conditions such as Alzheimer’s disease. This mini-review focuses on the effects of ethanolamine in the CNS and highlights the possible implications of these effects for drug design.


Molecules ◽  
2020 ◽  
Vol 25 (9) ◽  
pp. 2104 ◽  
Author(s):  
Eleonora Ficiarà ◽  
Shoeb Anwar Ansari ◽  
Monica Argenziano ◽  
Luigi Cangemi ◽  
Chiara Monge ◽  
...  

Magnetic Oxygen-Loaded Nanobubbles (MOLNBs), manufactured by adding Superparamagnetic Iron Oxide Nanoparticles (SPIONs) on the surface of polymeric nanobubbles, are investigated as theranostic carriers for delivering oxygen and chemotherapy to brain tumors. Physicochemical and cyto-toxicological properties and in vitro internalization by human brain microvascular endothelial cells as well as the motion of MOLNBs in a static magnetic field were investigated. MOLNBs are safe oxygen-loaded vectors able to overcome the brain membranes and drivable through the Central Nervous System (CNS) to deliver their cargoes to specific sites of interest. In addition, MOLNBs are monitorable either via Magnetic Resonance Imaging (MRI) or Ultrasound (US) sonography. MOLNBs can find application in targeting brain tumors since they can enhance conventional radiotherapy and deliver chemotherapy being driven by ad hoc tailored magnetic fields under MRI and/or US monitoring.


1908 ◽  
Vol 54 (226) ◽  
pp. 560-561
Author(s):  
David Orr ◽  
R. G. Rows

At a quarterly meeting of this Association held last year at Nottingham, we showed the results of our experiments with toxins upon the spinal cord and brain of rabbits. Our main conclusion was, that the central nervous system could be infected by toxins passing up along the lymph channels of the perineural sheath. The method we employed in our experiments consisted in placing a celloidin capsule filled with a broth culture of an organism under the sciatic nerve or under the skin of the cheek; and we invariably found a resulting degeneration in the spinal cord or brain, according to the situation of the capsule. These lesions we found to be identical in morphological type and anatomical distribution with those found in the cord of early tabes dorsalis and in the brain and cord of general paralysis of the insane. The conclusion suggested by our work was that these two diseases, if toxic, were most probably infections of lymphogenous origin.


Sign in / Sign up

Export Citation Format

Share Document