Inhibition of the preoptic area and anterior hypothalamus by tetrodotoxin alters thermoregulatory functions in exercising rats

2005 ◽  
Vol 98 (4) ◽  
pp. 1458-1462 ◽  
Author(s):  
Hiroshi Hasegawa ◽  
Takayuki Ishiwata ◽  
Takehito Saito ◽  
Toru Yazawa ◽  
Yasutsugu Aihara ◽  
...  

We have previously demonstrated a functional role of the preoptic area and anterior hypothalamus (PO/AH) in thermoregulation in freely moving rats at various temperature conditions by using microdialysis and biotelemetry methods. In the present study, we perfused tetrodotoxin (TTX) solution into the PO/AH to investigate whether this manipulation can modify thermoregulation in exercising rats. Male Wistar rats were trained for 3 wk by treadmill running. Body core temperature (Tb), heart rate (HR), and tail skin temperature (Ttail) were measured. Rats ran for 120 min at speed of 10 m/min, with TTX (5 μM) perfused into the left PO/AH during the last 60 min of exercise through a microdialysis probe (control, n = 12; TTX, n = 12). Tb, HR, and Ttail increased during the first 20 min of exercise. Thereafter, Tb, HR, and Ttail were stable in both groups. Perfusion of TTX into the PO/AH evoked an additional rise in Tb (control: 38.2 ± 0.1°C, TTX: 39.3 ± 0.2°C; P < 0.001) with a significant decrease in Ttail (control: 31.2 ± 0.5°C, TTX: 28.3 ± 0.7°C; P < 0.01) and a significant increase in HR (control: 425.2 ± 12 beats/min, TTX: 502.1 ± 13 beats/min; P < 0.01). These results suggest that the TTX-induced hyperthermia was the result of both an impairment of heat loss and an elevation of heat production during exercise. We therefore propose the PO/AH as an important thermoregulatory site in the brain during exercise.

2001 ◽  
Vol 306 (1-2) ◽  
pp. 126-128 ◽  
Author(s):  
Takayuki Ishiwata ◽  
Hiroshi Hasegawa ◽  
Mikinobu Yasumatsu ◽  
Fuminori Akano ◽  
Toru Yazawa ◽  
...  

2005 ◽  
Vol 99 (4) ◽  
pp. 1397-1401 ◽  
Author(s):  
Hiroshi Hasegawa ◽  
Romain Meeusen ◽  
Sophie Sarre ◽  
Marc Diltoer ◽  
Maria Francesca Piacentini ◽  
...  

The purpose of the present study was to examine the effects of an acute dose of the dual dopamine (DA) and norepinephrine (NE) reuptake inhibitor bupropion (Bup) on brain (Tbrain), body core (Tcore), and tail skin (Ttail) temperature in freely moving rats and to simultaneously monitor the extracellular neurotransmitter concentrations in the preoptic area and anterior hypothalamus (PO/AH). A microdialysis probe was inserted in the PO/AH, and samples for NE, DA, and serotonin (5-HT) were collected every 20 min before and after the injection of 17 mg/kg of Bup, for a total sampling time of 180 min. Tcore was monitored using a biotelemetry system. Tbrain and Ttail, an index of heat loss response, were also measured. Both NE and DA levels in the PO/AH significantly increased after Bup injection compared with the baseline levels, reaching ∼450 and 230%, respectively, 40 min after injection. There was no effect on 5-HT release. The neurotransmitter changes were accompanied by a significant decrease in Ttail and an increase in both Tbrain and Tcore compared with the baseline levels. The present results demonstrate that inhibition of NE and DA reuptake suppresses heat loss mechanisms and elevates Tbrain and Tcore in freely moving rats.


2002 ◽  
Vol 325 (3) ◽  
pp. 167-170 ◽  
Author(s):  
Takayuki Ishiwata ◽  
Hiroshi Hasegawa ◽  
Toru Yazawa ◽  
Minoru Otokawa ◽  
Yasutsugu Aihara

1998 ◽  
Vol 275 (1) ◽  
pp. R63-R68 ◽  
Author(s):  
Christopher T. Simons ◽  
Vladimir A. Kulchitsky ◽  
Naotoshi Sugimoto ◽  
Louis D. Homer ◽  
Miklos Székely ◽  
...  

Recent evidence has suggested a role of abdominal vagal afferents in the pathogenesis of the febrile response. The abdominal vagus consists of five main branches (viz., the anterior and posterior celiac branches, anterior and posterior gastric branches, and hepatic branch). The branch responsible for transducing a pyrogenic signal from the periphery to the brain has not as yet been identified. In the present study, we address this issue by testing the febrile responsiveness of male Wistar rats subjected to one of four selective vagotomies: celiac (CBV), gastric (GBV), hepatic (HBV), or sham (SV). In the case of CBV, GBV, and HBV, only the particular vagal branch(es) was cut; for SV, all branches were left intact. After the postsurgical recovery (26–29 days), the rats had a catheter implanted into the jugular vein. On days 29–32, their colonic temperature (Tc) responses to a low dose (1 μg/kg) of Escherichia colilipopolysaccharide (LPS) were studied. Three days later, the animals were subjected to a 24-h food and water deprivation, and the effectiveness of the four vagotomies to induce gastric food retention, pancreatic hypertrophy, and impairment of the portorenal osmotic reflex was assessed by weighing the stomach and pancreas and measuring the specific gravity of bladder urine, respectively. Stomach mass, pancreas mass, and urine density successfully separated the four experimental groups into four distinct clusters, thus confirming that each type of vagotomy had a different effect on the indexes measured. The Tc responses of SV, CBV, and GBV rats to LPS did not differ and were characterized by a latency of ∼40 min and a maximal rise of 0.7 ± 0.1, 0.6 ± 0.1, and 0.9 ± 0.2°C, respectively. The fever response of the HBV rats was different; practically no Tc rise occurred (0.1 ± 0.2°C). The HBV appeared to be the only selective abdominal vagotomy affecting the febrile responsiveness. We conclude, therefore, that the hepatic vagus plays an important role in the transduction of a pyrogenic signal from the periphery to the brain.


1976 ◽  
Vol 40 (4) ◽  
pp. 543-548 ◽  
Author(s):  
R. W. Carithers ◽  
R. C. Seagrave

Extreme whole-body hyperthermia was achieved without lasting side effects in canines by elevating body core temperature to 42 degrees C, using a warm water bath. Cold water irrigation of the nasal alar fold permitted an additional core temperature elevation of 0.5–1.0 degrees C above brain temperature for periods up to 1.5 h. The brain-core temperature differential was maintained by a physiological arteriovenous heat exchanger located at the base of the brain. The maximum tolerable core temperature for the 21 nonirrigated dogs was 42 degrees C for 60–90 min, whereas that for the 28 irrigated dogs was 42.5–43 degrees C for similar time intervals. A mathematical model of the total heat transfer system described the observed dynamic temperature responses. It was the solution of a differential equation which fit the normalized experimental data points and predicted reasonable values for known and unknown experimental parameters.


2016 ◽  
Vol 94 (10) ◽  
pp. 1074-1082 ◽  
Author(s):  
Dragan Hrncic ◽  
Jelena Mikić ◽  
Aleksandra Rasic-Markovic ◽  
Milica Velimirović ◽  
Tihomir Stojković ◽  
...  

The aim of this study was to examine the effects of a methionine-enriched diet on anxiety-related behavior in rats and to determine the role of the brain oxidative status in these alterations. Adult male Wistar rats were fed from the 30th to 60th postnatal day with standard or methionine-enriched diet (double content comparing with standard diet: 7.7 g/kg). Rats were tested in open field and light–dark tests and afterwards oxidative status in the different brain regions were determined. Hyperhomocysteinemia induced by methionine-enriched diet in this study decreased the number of rearings, as well as the time that these animals spent in the center of the open field, but increased index of thigmotaxy. Oxidative status was selectively altered in the examined regions. Lipid peroxidation was significantly increased in the cortex and nc. caudatus of rats developing hyperhomocysteinemia, but unaltered in the hippocampus and thalamus. Based on the results of this research, it could be concluded that hyperhomocysteinemia induced by methionine nutritional overload increased anxiety-related behavior in rats. These proanxiogenic effects could be, at least in part, a consequence of oxidative stress in the rat brain.


1997 ◽  
Vol 273 (2) ◽  
pp. R777-R783 ◽  
Author(s):  
A. A. Romanovsky ◽  
V. A. Kulchitsky ◽  
C. T. Simons ◽  
N. Sugimoto ◽  
M. Szekely

The repeatedly observed attenuation of fever in vagotomized rats has been accepted as evidence of an essential role of vagal afferents in the transduction of pyrogenic signals from the periphery to the brain. If, however, the general condition of a vagotomized animal is poor (the usual case) and accompanied by malnutrition and body mass loss (common complications of vagotomy), the febrile responsiveness can be suppressed not because of the lack of vagal afferentation, but rather secondarily to a malnutrition-associated thermogenic incompetence. In the present study, we addressed this dilemma. Male Wistar rats were subjected to subdiaphragmatic vagotomy (or sham surgery) and, 24 days later, catheterized in the jugular vein. Postsurgically, the rats were closely watched and fed highly palatable food. Their febrile responsiveness [colonic (Tc) and tail skin (Tsk) temperature responses] to Escherichia coli lipopolysaccharide (LPS: 1 microgram/kg i.v.) was tested on day 27 postvagotomy. To verify the completeness of vagotomy, each rat was food deprived for 24 h and then euthanized; its stomach's evacuatory function was assessed by weighing the organ. One month postsurgery, both food consumption and body mass of the vagotomized rats (33 +/- 2 g/day and 313 +/- 4 g, respectively) were similar to the control values (30 +/- 1 g/day and 315 +/- 8 g). In the sham rats, LPS induced a monophasic Tc rise of 0.5 +/- 0.3 degree C at 70 min postinjection (peak), preceded by a fall in Tsk. Neither this Tsk fall (tail skin vasoconstriction) nor the resultant fever occurred in the vagotomized rats; at 70 min, Tc change was -0.1 +/-0.1 degree C. The gastric mass (4.1 +/- 0.5 g in the vagotomized vs. 1.8 +/- 0.1 g in sham rats) indicated the effectiveness of vagotomy. In sum, although the vagotomy-associated malnutrition was successfully prevented with special perioperative care, the vagotomized animals still did not respond to LPS with fever. Malnutrition is, therefore, unlikely to constitute the main reason of the febrile irresponsiveness of vagotomized rats.


Perfusion ◽  
2019 ◽  
Vol 35 (2) ◽  
pp. 96-103 ◽  
Author(s):  
Seyed Mohammad Seyedsaadat ◽  
Silvana F Marasco ◽  
David J Daly ◽  
Robin McEgan ◽  
James Anderson ◽  
...  

Background/objective: Reduction of brain temperature remains the most common method of neuroprotection against ischemic injury employed during cardiac surgery. However, cooling delivered via the cardiopulmonary bypass circuit is brief and cooling the body core along with the brain has been associated with a variety of unwanted effects. This study investigated the feasibility and safety of a novel selective brain cooling approach to induce rapid, brain-targeted hypothermia independent of the cardiopulmonary bypass circuit. Methods: This first-in-human feasibility study enrolled five adults undergoing aortic valve replacement with cardiopulmonary bypass support. During surgery, the NeuroSave system circulated chilled saline within the pharynx and upper esophagus. Brain and body core temperature were continuously monitored. Adverse effects, cardiopulmonary function, and device function were noted. Results: Patient 1 received cooling fluid for an insignificant period, and Patients 2-5 successfully underwent the cooling procedure using the NeuroSave system for 56-89 minutes. Cooling fluid was 12°C for Patients 1-3, 6°C for Patient 4, and 2°C for Patient 5. There were no NeuroSave-related adverse events and no alterations in cardiopulmonary function during NeuroSave use. Brain temperature decreased by 3°C within 15 minutes and remained at least 3.5°C colder than the body core. During a brief episode of hypotension in one patient, the brain cooled an additional 4°C in 2 minutes, briefly reaching 27.4°C. Conclusion: The NeuroSave system can induce rapid brain-targeted hypothermia and simultaneously maintain a favorable body–brain temperature gradient, even during hypotension. Further studies are required to evaluate the function of the system during longer periods of use.


1998 ◽  
Vol 275 (1) ◽  
pp. R286-R290 ◽  
Author(s):  
Akira Takamata ◽  
Kei Nagashima ◽  
Hiroshi Nose ◽  
Taketoshi Morimoto

To elucidate the role of increased plasma osmolality (Posmol), which occurs during exercise in the regulation of cutaneous vasodilation (CVD) during exercise, we determined the relationship between the change in esophageal temperature (ΔTes) required to elicit CVD (ΔTes threshold for CVD) and Posmol during light and moderate exercise (30 and 55% of peak oxygen consumption, respectively) and passive body heating. Then we compared the relationship with the data obtained in our previous study [A. Takamata, K. Nagashima, H. Nose, and T. Morimoto. Am. J. Physiol. 273 ( Regulatory Integrative Comp. Physiol.42): R197–R204, 1997], in which we determined the relationships during passive body heating following isotonic (0.9% NaCl) or hypertonic (2 or 3% NaCl) saline infusions in the same subjects. Posmol values at 5 min after the onset of exercise were 287.5 ± 0.9 mosmol/kgH2O during light exercise and 293.0 ± 1.2 mosmol/kgH2O during moderate exercise. Posmol just before passive body heating was 289.9 ± 1.4 mosmol/kgH2O. The ΔTes threshold for CVD was 0.09 ± 0.05°C during light exercise, 0.31 ± 0.09°C during moderate exercise, and 0.10 ± 0.05°C during passive body heating. The relationship between the ΔTes threshold for CVD and Posmol was shown to be on the same regression line both during exercise and during passive body heating with or without infusions [A. Takamata, K. Nagashima, H. Nose, and T. Morimoto. Am. J. Physiol. 273 ( Regulatory Integrative Comp. Physiol.42): R197–R204, 1997]. Our data suggest that the elevated body core temperature threshold for CVD during exercise could be the result of increased Posmol induced by exercise and is not due to reduced plasma volume or the intensity of the exercise itself.


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