Relative contributions of a CVO and the microvascular bed to delivery of blood-borne IL-1α to the brain

1998 ◽  
Vol 275 (2) ◽  
pp. E207-E212 ◽  
Author(s):  
Lawrence M. Maness ◽  
Abba J. Kastin ◽  
William A. Banks

Diffusion from brain regions lacking a blood-brain barrier (BBB) and saturable transport across capillaries are possible pathways for the entry of blood-borne interleukin-1α into the central nervous system (CNS). To assess the involvement of these putative routes, mice received intravenous injections of radioiodinated interleukin-1α, and their brains were subjected to emulsion autoradiography. The resulting patterns of silver grain distribution showed that diffusion of interleukin-1α from the choroid plexus and the subfornical organ was greatly restricted. These restrictive properties were quantified by the determination of D1/2 values, the distances needed for the concentration of silver grains to decrease by one-half. Within several brain regions, a subset of the microvasculature indicated transport of interleukin-1α across the BBB. Individual microvessels showed different patterns of transport ranging from robust to absent. The high degree of containment of blood-borne interleukin-1α within the regions lacking a BBB indicates that these sites cannot account for total delivery of the cytokine into the brain and suggests instead that the microvascular network may serve as the major route of entry into the CNS.

Author(s):  
Sarah F. Beul ◽  
Alexandros Goulas ◽  
Claus C. Hilgetag

AbstractStructural connections between cortical areas form an intricate network with a high degree of specificity. Many aspects of this complex network organization in the adult mammalian cortex are captured by an architectonic type principle, which relates structural connections to the architectonic differentiation of brain regions. In particular, the laminar patterns of projection origins are a prominent feature of structural connections that varies in a graded manner with the relative architectonic differentiation of connected areas in the adult brain. Here we show that the architectonic type principle is already apparent for the laminar origins of cortico-cortical projections in the immature cortex of the macaque monkey. We find that prenatal and neonatal laminar patterns correlate with cortical architectonic differentiation, and that the relation of laminar patterns to architectonic differences between connected areas is not substantially altered by the complete loss of visual input. Moreover, we find that the degree of change in laminar patterns that projections undergo during development varies in proportion to the relative architectonic differentiation of the connected areas. Hence, it appears that initial biases in laminar projection patterns become progressively strengthened by later developmental processes. These findings suggest that early neurogenetic processes during the formation of the brain are sufficient to establish the characteristic laminar projection patterns. This conclusion is in line with previously suggested mechanistic explanations underlying the emergence of the architectonic type principle and provides further constraints for exploring the fundamental factors that shape structural connectivity in the mammalian brain.


2019 ◽  
Vol 116 (15) ◽  
pp. 7503-7512 ◽  
Author(s):  
Liching Lo ◽  
Shenqin Yao ◽  
Dong-Wook Kim ◽  
Ali Cetin ◽  
Julie Harris ◽  
...  

Type 1 estrogen receptor-expressing neurons in the ventrolateral subdivision of the ventromedial hypothalamus (VMHvlEsr1) play a causal role in the control of social behaviors, including aggression. Here we use six different viral-genetic tracing methods to systematically map the connectional architecture of VMHvlEsr1 neurons. These data reveal a high level of input convergence and output divergence (“fan-in/fan-out”) from and to over 30 distinct brain regions, with a high degree (∼90%) of bidirectionality, including both direct as well as indirect feedback. Unbiased collateralization mapping experiments indicate that VMHvlEsr1 neurons project to multiple targets. However, we identify two anatomically distinct subpopulations with anterior vs. posterior biases in their collateralization targets. Nevertheless, these two subpopulations receive indistinguishable inputs. These studies suggest an overall system architecture in which an anatomically feed-forward sensory-to-motor processing stream is integrated with a dense, highly recurrent central processing circuit. This architecture differs from the “brain-inspired,” hierarchical feed-forward circuits used in certain types of artificial intelligence networks.


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.


2019 ◽  
Vol 63 (2) ◽  
pp. 285-292
Author(s):  
Ning Ma ◽  
Xin Li ◽  
Hong-bin Wang ◽  
Li Gao ◽  
Jian-hua Xiao

AbstractIntroduction:Tiletamine-xylazine-tramadol (XFM) has few side effects and can provide good sedation and analgesia. Adenosine 5’-monophosphate-activated protein kinase (AMPK) can attenuate trigeminal neuralgia. The study aimed to investigate the effects of XFM and its specific antagonist on AMPK in different regions of the brain.Material and Methods:A model of XFM in the rat was established. A total of 72 Sprague Dawley (SD) rats were randomly divided into three equally sized groups: XFM anaesthesia (M group), antagonist (W group), and XFM with antagonist interactive groups (MW group). Eighteen SD rats were in the control group and were injected intraperitoneally with saline (C group). The rats were sacrificed and the cerebral cortex, cerebellum, hippocampus, thalamus, and brain stem were immediately separated, in order to detect AMPKα mRNA expression by quantitative PCR.Results:XFM was able to increase the mRNA expression of AMPKα1 and AMPKα2 in all brain regions, and the antagonist caused the opposite effect, although the effects of XFM could not be completely reversed in some areas.Conclusion:XFM can influence the expression of AMPK in the central nervous system of the rat, which can provide a reference for the future development of anaesthetics for animals.


2021 ◽  
Vol 15 ◽  
Author(s):  
Jérôme Wahis ◽  
Matthew G. Holt

Noradrenaline is a major neuromodulator in the central nervous system (CNS). It is released from varicosities on neuronal efferents, which originate principally from the main noradrenergic nuclei of the brain – the locus coeruleus – and spread throughout the parenchyma. Noradrenaline is released in response to various stimuli and has complex physiological effects, in large part due to the wide diversity of noradrenergic receptors expressed in the brain, which trigger diverse signaling pathways. In general, however, its main effect on CNS function appears to be to increase arousal state. Although the effects of noradrenaline have been researched extensively, the majority of studies have assumed that noradrenaline exerts its effects by acting directly on neurons. However, neurons are not the only cells in the CNS expressing noradrenaline receptors. Astrocytes are responsive to a range of neuromodulators – including noradrenaline. In fact, noradrenaline evokes robust calcium transients in astrocytes across brain regions, through activation of α1-adrenoreceptors. Crucially, astrocytes ensheath neurons at synapses and are known to modulate synaptic activity. Hence, astrocytes are in a key position to relay, or amplify, the effects of noradrenaline on neurons, most notably by modulating inhibitory transmission. Based on a critical appraisal of the current literature, we use this review to argue that a better understanding of astrocyte-mediated noradrenaline signaling is therefore essential, if we are ever to fully understand CNS function. We discuss the emerging concept of astrocyte heterogeneity and speculate on how this might impact the noradrenergic modulation of neuronal circuits. Finally, we outline possible experimental strategies to clearly delineate the role(s) of astrocytes in noradrenergic signaling, and neuromodulation in general, highlighting the urgent need for more specific and flexible experimental tools.


Author(s):  
Sahib S. Khalsa ◽  
Justin S. Feinstein

A regulatory battle for control ensues in the central nervous system following a mismatch between the current physiological state of an organism as mapped in viscerosensory brain regions and the predicted body state as computed in visceromotor control regions. The discrepancy between the predicted and current body state (i.e. the “somatic error”) signals a need for corrective action, motivating changes in both cognition and behavior. This chapter argues that anxiety disorders are fundamentally driven by somatic errors that fail to be adaptively regulated, leaving the organism in a state of dissonance where the predicted body state is perpetually out of line with the current body state. Repeated failures to quell somatic error can result in long-term changes to interoceptive circuitry within the brain. This chapter explores the neuropsychiatric sequelae that can emerge following chronic allostatic dysregulation of somatic errors and discusses novel therapies that might help to correct this dysregulation.


1995 ◽  
Vol 1995 ◽  
pp. 204-204
Author(s):  
E.A. Azaga ◽  
R.G. Rodway

The long distance transport of sheep before slaughter is at present a very important topic in animal welfare. However, Modulation of opioid receptors can be influenced by chronic treatment with opioid agonists and antagonists (Blanchard, and Chang, 1988). Similarly, opioid receptors can be up or down-regulated by stressful stimuli such as restraint, electric footshock or social isolation and housing (Zeman et al., 1988 and Zanella et al., 1991). The present study was carried out to assess the effects of transport stress on the properties of one class of opioid peptide receptor in the brain of sheep after transport stress. Opioid peptides such as β-endorphin are released by the central nervous system during application of stresses such as transport. They are believed to exert analgesic properties and their effectiveness depends partly on the concentration (Bmax) and affinity (Kd) of their receptors. µ-Opioid receptors are found in various brain regions and are selective for endorphins and similar peptides.


2020 ◽  
Vol 2020 (9) ◽  
Author(s):  
Thomas Quinn ◽  
Manish Jain ◽  
Ming-Te Lee

ABSTRACT Acute Promyelocytic Leukaemia (APML) is a subtype of Acute Myeloid Leukaemia (AML), responsible for around 10% of cases of the disease in adults. Extra medullary disease (EMD) occurs infrequently in APML, but where EMD does occur, the central nervous system is one of the most commonly infiltrated sites. Our case describes a man in his 40s undergoing post-therapy surveillance for APML who presented to follow-up clinic with a headache, which was ultimately found to be caused by a tumour comprised of APML cells. His case presented a diagnostic challenge due to the benign appearances of the lesion on initial computed tomography brain imaging and the non-diagnostic cerebrospinal fluid analysis. The diagnostic difficulties described in our case emphasizes that clinicians working with APML patients must approach new neurological symptoms with a high degree of suspicion to prevent diagnostic delay.


1940 ◽  
Vol 72 (1) ◽  
pp. 49-67 ◽  
Author(s):  
Max Theiler ◽  
Sven Gard

1. The two strains of virus named GD VII and FA, respectively, accidentally discovered during experiments with yellow fever, have been shown to be immunologically related to each other, as well as to the virus of mouse encephalomyelitis. 2. Infection of the central nervous system can be produced with both strains by intracerebral, intranasal, or intraperitoneal inoculations. The cardinal symptom produced by the GD VII strain of virus by all three methods of inoculation is a flaccid paralysis of the limbs. The symptoms produced by the FA strain are referable to lesions of the brain when infection is produced by intracerebral and intranasal inoculation. Following intraperitoneal inoculation of the FA strain of virus, however, a flaccid paralysis is usually produced. 3. By the use of graded collodion membranes the particle size of the virus of mouse encephalomyelitis has been shown to be from 9 to 13 mµ 4. The stability of the virus at different hydrogen ion concentrations has been tested. It has been found that there are two optima of stability, one at about pH 8.0 and the other at pH 3.3. 5. The virus is readily inactivated at 37°C. by 1 per cent hydrogen peroxide. 6. Of organic solvents tested, ether had no action, whereas ethyl alcohol in 20 per cent concentration almost completely inactivated the virus after 45 minutes in the cold. 7. The virus can be precipitated by means of ammonium sulfate. 8. With increasing age mice acquire a relative resistance to the virus. 9. Immunity to a subsequent intracerebral inoculation can be produced by intraperitoneal, as well as intranasal, administrations of relatively large amounts of virus. 10. Mice infected by the intracerebral inoculation of a relatively avirulent virus acquire a high degree of immunity to a subsequent inoculation of a highly virulent strain. 11. The course of infection in mice following intracerebral, intranasal, and intraperitoneal inoculation of the FA strain of virus has been studied.


1981 ◽  
Vol 29 (1A_suppl) ◽  
pp. 117-124 ◽  
Author(s):  
L.W. Swanson

The major advantages and disadvantages of the autoradiographic method for tracing pathways in the central nervous system have become clear in the decade since its introduction. Attention is focused here on two major problems associated with the interpretation of autoradiographic experiments. First, it is often difficult to determine the effective size of an injection site, which may be different for different projections in the same experiment. Quantitative evidence presented here also shows that the apparent size of injection sites in the hippocampus decreases considerably in diameter 1 to 2 weeks after the injections are made. And second, the morphology of labeled pathways must be inferred from a pattern of silver grains lying over the tissue section. Several examples are used to illustrate the point that the autoradiographic method should be used in conjunction with retrograde transport, immunohistochemical, and electron microscopic techniques to investigate the origin, course, and synaptic relationships of individual pathways in the brain and spinal cord.


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