Role of the anteroventral third ventricle region in fever in sheep

1987 ◽  
Vol 65 (6) ◽  
pp. 1255-1260 ◽  
Author(s):  
C. M. Blatteis ◽  
J. R. S. Hales ◽  
M. J. McKinley ◽  
A. A. Fawcett
Keyword(s):  
Anterior Commissure ◽  
Third Ventricle ◽  
Endogenous Pyrogen ◽  
Febrile Response ◽  
Vascular Plexus ◽  
Organum Vasculosum Laminae Terminalis ◽  
Frontal Wall ◽  
Escherichia Coli Lipopolysaccharide ◽  
Lateral Walls

Ablation of the anteroventral third ventricle (AV3V) region, which includes the organum vasculosum laminae terminalis (OVLT), blocks the febrile response of guinea pigs to systemically injected endotoxin; by contrast, discrete lesions of the OVLT transiently enhance fever in rabbits and rats. To assess whether separate subdivisions of the AV3V may mediate these different effects, the thermal responses to Escherichia coli lipopolysaccharide (LPS, 0.25 μg/kg, i.v.) were measured in eight sheep before and 12–13 days after placement of lesions at various levels within the AV3V. The responses of four of these sheep to crude homologous endogenous pyrogen (EP, 1–2 mL, i.c.v.) were also evaluated. Additionally, five other sheep were tested with LPS 2–8 months postlesion. All the experiments were performed at thermoneutrality. Sheep were used because most of the frontal wall of their 3V forms an elongated OVLT consisting of an avascular body and a vascular base. The animals were classified postmortem according to the extent of tissue ablated. Lesion overlap analyses showed that (i) medial lesions which extended from the floor of the 3V to the anterior commissure and laterally into adjacent preoptic periventricular tissue were associated with significantly depressed fever after LPS (n = 2); (ii) comparable lesions, but which excluded the ventral portion of the AV3V, i.e., the base of the OVLT, did not alter the magnitude of the febrile response to LPS (n = 4); (iii) lesions of the lateral walls of the 3V and (or) of the adjacent medial preoptic and anterior hypothalamic areas but excluding the frontal 3V wall also did not affect fever height after LPS (n = 7). Damage to aspects of the walls of the lateral ventricles attenuated the febrile response to EP i.c.v. (n = 3). Hence, although no separate fever-inhibiting and fever-enhancing regions were found within the AV3V, these results indicate that the ventral portion of the AV3V, i.e., the vascular plexus of the OVLT, is critical for normal fever development in sheep.

Peri-OVLT E-series prostaglandins and core temperature do not increase after intravenous IL-1β in pregnant rats

2002 ◽  
Vol 93 (2) ◽  
pp. 531-536 ◽  
Author(s):  
James E. Fewell ◽  
Heather L. Eliason ◽  
Roland N. Auer
Keyword(s):  
Core Temperature ◽  
Intravenous Administration ◽  
Sprague Dawley ◽  
Endogenous Pyrogen ◽  
Febrile Response ◽  
Pregnant Rats ◽  
Organum Vasculosum Laminae Terminalis ◽  
Sprague Dawley Rats ◽  
Maternal Adaptation ◽  
Near Term

Rats have an attenuated febrile response to endogenous pyrogen near the term of pregnancy. Given the fundamental role of E-series prostaglandins (PGEs) in mediating the febrile response to blood-borne endogenous pyrogen, the present experiments were carried out to determine whether PGEs increase in the area surrounding the organum vasculosum laminae terminalis (peri-OVLT) of near-term pregnant (P) rats as in nonpregnant (NP) rats after intravenous (iv) administration of recombinant rat interleukin-1β (rrIL-1β). Core temperature was measured by telemetry and peri-OVLT interstitial fluid was sampled in 12 NP and 12 P chronically instrumented, Sprague-Dawley rats by microdialysis for determination of total PGEs by radioimmunoassay. Basal core temperatures were higher in NP compared with P rats (NP 37.9°C ± 0.5, P 36.9°C ± 0.4; P < 0.05), but basal peri-OVLT PGEs were similar in both groups (NP 260 ± 153 pg/ml, P 278 ± 177 pg/ml; P =not significant). Intravenous administration of rrIL-1β to NP rats produced a significant increase in core temperature with a latency, magnitude, and duration of 10 min, 0.87°C, and at least 170 min, respectively; peri-OVLT PGEs were increased significantly by 30 min and averaged 270% above basal levels throughout the experiment. In P rats, however, neither core temperature nor peri-OVLT PGEs increased significantly after iv administration of rrIL-1β. Intravenous administration of vehicle did not significantly alter core temperature or peri-OVLT PGEs in either group of rats. Thus peri-OVLT PGEs do not increase in P rats as they do in NP rats after iv administration of rrIL-1β. The mechanism of this interesting component of the maternal adaptation to pregnancy, which likely plays a major role in mediating the attenuated febrile response to endogenous pyrogen near the term of pregnancy, warrants further investigation.

scholarly journals Interleukin (IL)-6, But Not IL-1, Induction in the Brain Downstream of Cyclooxygenase-2 Is Essential for the Induction of Febrile Response against Peripheral IL-1α

Endocrinology ◽  
2004 ◽  
Vol 145 (11) ◽  
pp. 5044-5048 ◽  
Author(s):  
Kyoko Kagiwada ◽  
Dai Chida ◽  
Tomoya Sakatani ◽  
Masahide Asano ◽  
Aya Nambu ◽  
...  
Keyword(s):  
Prostaglandin E2 ◽  
Cyclooxygenase 2 ◽  
Signaling Cascade ◽  
Endogenous Pyrogen ◽  
Febrile Response ◽  
Cox 2 ◽  
The Brain ◽  
Deficient Mice

Abstract IL-1 is an endogenous pyrogen produced upon inflammation or infection. Previously, we showed that, upon injection with turpentine, IL-1 is induced in the brain in association with the development of fever. The role of endogenous IL-1 in the brain and the signaling cascade to activate thermosensitive neurons, however, remain to be elucidated. In this report, febrile response was analyzed after peripheral injection of IL-1α. We found that a normal febrile response was induced even in IL-1α/β-deficient mice, indicating that production of IL-1 in the brain is not necessarily required for the response. In contrast, IL-6-deficient mice did not exhibit a febrile response. Cyclooxygenase (Cox)-2 expression in the brain was strongly induced 1.5 h after injection of IL-1α, whereas IL-6 expression was observed 3 h after the injection. Cox-2 expression in the brain was not influenced by IL-6 deficiency, whereas indomethacin, an inhibitor of cyclooxygenases, completely inhibited induction of IL-6. These observations suggest a mechanism of IL-1-induced febrile response in which IL-1 in the blood activates Cox-2, with the resulting prostaglandin E2 inducing IL-6 in the brain, leading to the development of fever.

Evidence that platelet-derived growth factor may be a novel endogenous pyrogen in the central nervous system

2000 ◽  
Vol 278 (5) ◽  
pp. R1275-R1281 ◽  
Author(s):  
Irene R. Pelá ◽  
Márcia E. S. Ferreira ◽  
Miriam C. C. Melo ◽  
Carlos A. A. Silva ◽  
Márcio M. Coelho ◽  
...  
Keyword(s):  
Central Nervous System ◽  
Nervous System ◽  
Growth Factor ◽  
Third Ventricle ◽  
Platelet Derived Growth Factor ◽  
Febrile Response ◽  
The Central Nervous System ◽  
Factor Α ◽  
Colonic Temperature

Platelet-derived growth factor (PDGF) exerts neurotrophic and neuromodulatory actions in the mammalian central nervous system (CNS). Like the cytokines, PDGF primarily signals through tyrosine phosphorylation-dependent pathways that activate multiple intracellular molecules including Janus family kinases. We previously showed that microinjection of PDGF-BB into the lateral ventricle induced a febrile response in rats that was reduced by pretreatment with Win 41662, a potent inhibitor of PDGF receptors (Pelá IR, Ferreira MES, Melo MCC, Silva CAA, and Valenzuela CF. Ann NY Acad Sci 856: 289–293, 1998). In this study, we further characterized the role of PDGF-BB in the febrile response in rats. Microinjection of PDGF-BB into the third ventricle produced a dose-dependent increase in colonic temperature that peaked 3–4 h postinjection. Win 41662 attenuated fever induced by intraperitoneal injection of bacterial lipopolysaccharide, suggesting that endogenous PDGF participates in the febrile response to this exogenous pyrogen. Importantly, febrile responses induced by tumor necrosis factor-α, interleukin-1β, and interleukin-6 were unchanged by Win 41662. Both indomethacin and dexamethasone blocked the PDGF-BB-induced increase in colonic temperature, and, therefore, we postulate that PDGF-BB may act via prostaglandin- and/or inducible enzyme-dependent pathways. Thus our findings suggest that PDGF-BB is an endogenous CNS mediator of the febrile response in rats.

Thermoregulation in the rabbit following intracranial injection of norepinephrine

1975 ◽  
Vol 229 (3) ◽  
pp. 676-682 ◽  
Author(s):  
E Preston
Keyword(s):  
Preoptic Area ◽  
Third Ventricle ◽  
Intraventricular Injection ◽  
Nerve Terminals ◽  
Cerebral Ventricles ◽  
Febrile Response ◽  
Conscious Rabbits ◽  
Hypothalamic Preoptic Area ◽  
A Site

The release of norepinephrine (NE) from nerve terminals in the anterior hypothalamic/preoptic area (AH/POA) of the rabbit may serve to raise body temperature. To further examine the putative neurotransmitter role of NE, bilateral microinjections of 5 or 10 mug NE were made into or near the AH/POA of 44 conscious rabbits exposed to an ambient temperature of 15 degrees C. Microinjections into the AH/POS did not cause fever; they either had no influence on thermoregulation or rapidly induced ear vasocilation and increased ear temperature accompanied by slight falls in rectal temperature. The latter averaged 0.32 degrees C (range: 0.16-0.45 degrees C) in 18 rabbits in which the effects were prominent. In contrast, the injection of 100 or 250 mug NE into the lateral cerebral ventricles of conscious rabbits in the 15 degrees C environment caused mean fevers of 0.62 +/- 0.0, and 1.04 +/- 0.14 degrees C (+/- SE, n equals 6), respectively, within 70 min. The febrile response to intraventricular injection of NE may be due to an action of the drug at a site other than the AH/POA. Alternatively, the response may depend critically on the particular distribution of NE that results from its diffusion from the third ventricle into the AH/POA.

Putative antihyperpyretic factor induced by LPS in spleen of guinea pigs

2005 ◽  
Vol 289 (3) ◽  
pp. R680-R687 ◽  
Author(s):  
Carlos Feleder ◽  
Vit Perlik ◽  
Ying Tang ◽  
Clark M. Blatteis
Keyword(s):  
Kupffer Cells ◽  
Guinea Pigs ◽  
Collateral Circulation ◽  
Splenic Vein ◽  
Inhibitory Factor ◽  
Febrile Response ◽  
Temperature Changes ◽  
The Core ◽  
Temporally Correlated

We reported previously that the onset of LPS-induced fever, irrespective of its route of administration, is temporally correlated with the appearance of LPS in the liver and that splenectomy significantly increases both the febrile response to LPS and the uptake of LPS by Kupffer cells (KC). To further evaluate the role of the spleen in LPS fever production, we ligated the splenic vein and, 7 and 30 days later, monitored the core temperature changes over 6 h after intraperitoneal (ip) injection of LPS (2 μg/kg). Both the febrile response and the uptake of LPS by KC were significantly augmented. Like splenectomy, splenic vein ligation (SVL) increased the febrile response and LPS uptake by KC until the collateral circulation developed, suggesting that the spleen may normally contribute an inhibitory factor that limits KC uptake of LPS and thus affects the febrile response. Subsequently, to verify the presence of this factor, we prepared splenic extracts from guinea pigs pretreated with LPS (8 μg/kg ip) or pyrogen-free saline, homogenized and ultrafiltered them, and injected them intravenously into splenectomized (Splex) guinea pigs pretreated with LPS (8 μg/kg ip). The results confirmed our presumption that the splenic extract from LPS-treated guinea pigs inhibits the exaggerated febrile response and the LPS uptake by the liver of Splex guinea pigs, indicating the presence of a putative splenic inhibitory factor, confirming the participation of the spleen in LPS-induced fever, and suggesting the existence of a novel antihyperpyretic mechanism. Preliminary data indicate that this factor is a lipid.

scholarly journals The Increase in Signaling by Kisspeptin Neurons in the Preoptic Area and Associated Changes in Clock Gene Expression That Trigger the LH Surge in Female Rats Are Dependent on the Facilitatory Action of a Noradrenaline Input

Endocrinology ◽  
2016 ◽  
Vol 157 (1) ◽  
pp. 323-335 ◽  
Author(s):  
Bruna Kalil ◽  
Aline B. Ribeiro ◽  
Cristiane M. Leite ◽  
Ernane T. Uchôa ◽  
Ruither O. Carolino ◽  
...  
Keyword(s):  
Gene Expression ◽  
Median Eminence ◽  
Preoptic Area ◽  
Clock Genes ◽  
Third Ventricle ◽  
Female Rats ◽  
Ovariectomized Rats ◽  
Lh Surge ◽  
Clock Gene Expression

Abstract In rodents, kisspeptin neurons in the rostral periventricular area of the third ventricle (RP3V) of the preoptic area are considered to provide a major stimulatory input to the GnRH neuronal network that is responsible for triggering the preovulatory LH surge. Noradrenaline (NA) is one of the main modulators of GnRH release, and NA fibers are found in close apposition to kisspeptin neurons in the RP3V. Our objective was to interrogate the role of NA signaling in the kisspeptin control of GnRH secretion during the estradiol induced LH surge in ovariectomized rats, using prazosin, an α1-adrenergic receptor antagonist. In control rats, the estradiol-induced LH surge at 17 hours was associated with a significant increase in GnRH and kisspeptin content in the median eminence with the increase in kisspeptin preceding that of GnRH and LH. Prazosin, administered 5 and 3 hours prior to the predicted time of the LH surge truncated the LH surge and abolished the rise in GnRH and kisspeptin in the median eminence. In the preoptic area, prazosin blocked the increases in Kiss1 gene expression and kisspeptin content in association with a disruption in the expression of the clock genes, Per1 and Bmal1. Together these findings demonstrate for the first time that NA modulates kisspeptin synthesis in the RP3V through the activation of α1-adrenergic receptors prior to the initiation of the LH surge and indicate a potential role of α1-adrenergic signaling in the circadian-controlled pathway timing of the preovulatory LH surge.

Ouabain- and central sodium-induced hypertension depend on the ventral anteroventral third ventricle region

1999 ◽  
Vol 276 (1) ◽  
pp. H63-H70 ◽  
Author(s):  
Shereeni J. Veerasingham ◽  
Frans H. H. Leenen
Keyword(s):  
Hypertonic Saline ◽  
Wistar Rats ◽  
Third Ventricle ◽  
Cardiovascular Responses ◽  
Ibotenic Acid ◽  
Air Jet ◽  
Artificial Cerebrospinal Fluid ◽  
Induced Hypertension ◽  
Chronic Infusion

To examine the role of the ventral anteroventral third ventricle (vAV3V) in the hypertension induced by chronic subcutaneous ouabain and intracerebroventricular hypertonic saline, neurons in this area were destroyed by microinjection of an excitotoxin, ibotenic acid. Sham-operated or lesioned Wistar rats were administered ouabain (50 μg/day) or placebo for 3 wk from subcutaneously implanted controlled release pellets or artificial cerebrospinal fluid (CSF) or CSF containing 0.8 mol/l NaCl (5 μl/h) infused intracerebroventricularly for 2 wk. At the end of the experiment, mean arterial pressure (MAP) and heart rate at rest and in response to ganglionic blockade by intravenous hexamethonium (30 mg/kg) were assessed. In rats infused with hypertonic saline, responses to air jet stress were also assessed. Baseline MAP in sham-operated rats receiving intracerebroventricular hypertonic saline or subcutaneous ouabain was significantly higher than in control rats (115 ± 1 vs. 97 ± 3 and 121 ± 3 vs. 103 ± 3 mmHg, respectively). vAV3V lesions abolished the increase in MAP elicited by chronic infusion of hypertonic saline or administration of ouabain. Sham-operated rats treated with hypertonic saline or ouabain exhibited significantly enhanced decreases in MAP to hexamethonium, but lesioned rats did not. Rats infused with hypertonic saline demonstrated enhanced responses to air jet stress that were similar in sham-operated and lesioned rats. These results demonstrate that neurons in the vAV3V are essential for the hypertension induced by intracerebroventricular hypertonic saline and subcutaneous ouabain, possibly by increasing sympathetic tone. Cardiovascular responses to air jet stress appear not to be mediated by the vAV3V.

scholarly journals STUDIES ON THE PATHOGENESIS OF FEVER WITH INFLUENZAL VIRUSES

1958 ◽  
Vol 107 (3) ◽  
pp. 383-401 ◽  
Author(s):  
Elisha Atkins ◽  
Wei Cheng Huang
Keyword(s):  
Newcastle Disease ◽  
Polymorphonuclear Leukocyte ◽  
Influenza A ◽  
Passive Transfer ◽  
Endogenous Pyrogen ◽  
Febrile Response ◽  
Essential Step ◽  
Intravenous Inoculation ◽  
Intraperitoneal Inoculation

A substance with pyrogenic properties appears in the blood streams of rabbits made febrile by the intravenous inoculation of the PR8 strain of influenza A and Newcastle disease viruses (NDV). By means of a technique involving passive transfer of sera from animals given virus to recipient rabbits, the titer of circulating pyrogen was found to be closely correlated with the course of fever produced by virus. Certain properties of the pyrogen are described which differentiate it from the originally injected virus and suggest that the induced pyrogen is of endogenous origin. These properties resemble those of endogenous pyrogens occurring in other forms of experimental fever. The source of virus-induced pyrogen is unknown. In vitro incubation of virus with various constituents of the circulation did not result in the appearance of endogenous pyrogen. Granulocytopenia induced by HN2 failed to influence either fever or the production of endogenous pyrogen in rabbits injected with NDV. Similarly, the intraperitoneal inoculation of NDV into prepared exudates did not modify the febrile response. These findings do not lend support to the possibility that the polymorphonuclear leukocyte is a significant source of endogenous pyrogen in virus-induced fever. It is concluded that the liberation of an endogenous pyrogen from some as yet undefined source is an essential step in the pathogenesis of fever caused by the influenza group of viruses.

The role of macrophages in the acute-phase response: SAA inducer is closely related to lymphocyte activating factor and endogenous pyrogen

1981 ◽  
Vol 63 (1) ◽  
pp. 164-176 ◽  
Author(s):  
Marcelo B. Sztein ◽  
Stefanie N. Vogel ◽  
Jean D. Sipe ◽  
Patrick A. Murphy ◽  
Steven B. Mizel ◽  
...  
Keyword(s):  
Acute Phase ◽  
Acute Phase Response ◽  
Phase Response ◽  
Endogenous Pyrogen

The organum vasculosum laminae terminalis in immune-to-brain febrigenic signaling: a reappraisal of lesion experiments

2003 ◽  
Vol 285 (2) ◽  
pp. R420-R428 ◽  
Author(s):  
Andrej A. Romanovsky ◽  
Naotoshi Sugimoto ◽  
Christopher T. Simons ◽  
William S. Hunter
Keyword(s):  
Side Effects ◽  
Isotonic Saline ◽  
Alternative Interpretation ◽  
Sprague Dawley ◽  
Febrile Response ◽  
Drinking Response ◽  
Organum Vasculosum Laminae Terminalis ◽  
Sprague Dawley Rats ◽  
Organum Vasculosum ◽  
The Brain

The organum vasculosum laminae terminalis (OVLT) has been proposed to serve as the interface for blood-to-brain febrigenic signaling, because ablation of this structure affects the febrile response. However, lesioning the OVLT causes many “side effects” not fully accounted for in the fever literature. By placing OVLT-lesioned rats on intensive rehydration therapy, we attempted to prevent these side effects and to evaluate the febrile response in their absence. After the OVLT of Sprague-Dawley rats was lesioned electrolytically, the rats were given access to 5% sucrose for 1 wk to stimulate drinking. Sucrose consumption and body mass were monitored. The animals were examined twice a day for signs of dehydration and treated with isotonic saline (50 ml/kg sc) when indicated. This protocol eliminated mortality but not several acute and chronic side effects stemming from the lesion. The acute effects included adipsia and gross (14% of body weight) emaciation; chronic effects included hypernatremia, hyperosmolality, a suppressed drinking response to hypertonic saline, and previously unrecognized marked (by ∼2°C) and long-lasting (>3 wk) hyperthermia. Because the hyperthermia was not accompanied by tail skin vasoconstriction, it likely reflected increased thermogenesis. After the rats recovered from the acute (but not chronic) side effects, their febrile response to IL-1β (500 ng/kg iv) was tested. The sham-operated rats developed typical monophasic fevers (∼0.5°C), the lesioned rats did not. However, the absence of the febrile response in the OVLT-lesioned rats likely resulted from the untreatable side effects. For example, hyperthermia at the time of pyrogen injection was high enough (39–40°C) to solely prevent fever from developing. Hence, the changed febrile responsiveness of OVLT-lesioned animals is given an alternative interpretation, unrelated to febrigenic signaling to the brain.

Sign in / Sign up

Export Citation Format

Share Document