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Cited by 68Thermal Regulation in MedicineThermoregulation and physiological responsesNeuroscience of respiration and sleep

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

Romanovsky, Andrej A., Sugimoto, Naotoshi, Simons, Christopher T., Hunter, William S.·2003·American Journal of Physiology-Regulatory, Integrative and Comparative Physiology
DOI 10.1152/ajpregu.00757.2002
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Abstract

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 approximately 2 degrees 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-1beta (500 ng/kg iv) was tested. The sham-operated rats developed typical monophasic fevers ( approximately 0.5 degrees 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 degrees 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.

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Authors
Romanovsky, A. A., Sugimoto, N., Simons, C. T., & Hunter, W. S.
Affiliations
St. Joseph's Hospital and Medical Center (US)
ORCID
Venue
American Journal of Physiology-Regulatory, Integrative and Comparative Physiology
Publisher
American Physiological Society
Published
2003-08
Volume
285
Issue
2
Pages
R420-R428
ISSN
  • 0363-6119 (ISSN-L)
  • 1522-1490
DOI
10.1152/ajpregu.00757.2002
OpenAlex
W2117227828
Cited by
68
References
78
Citations by year
2024: 2 · 2022: 1 · 2020: 1 · 2019: 1 · 2018: 2 · 2017: 1 · 2016: 3 · 2015: 2 · 2014: 7 · 2013: 4 · 2012: 3
FWCI
5.89
Type
journal article
Language
en
Open access
closed
Locations
  • American Journal of Physiology-Regulatory, Integrative and Comparative Physiology (publishedVersion)
  • PubMed (publishedVersion)
Funders
National Institute of Neurological Disorders and Stroke (R01NS041233, R01 NS 41233)
Topics
  • Health Sciences › Medicine › Critical Care and Intensive Care Medicine › Thermal Regulation in Medicine
  • Health Sciences › Medicine › Physiology › Thermoregulation and physiological responses
  • Life Sciences › Neuroscience › Endocrine and Autonomic Systems › Neuroscience of respiration and sleep
Keywords
organum vasculosum of the lamina terminalis, fever, electrolytic lesions, dehydration, adipsia, hypernatremia, hyperosmolarity, hyperthermia, thermogenesis, IL-1β, hypothalamic-pituitary-thyroid axis
MeSH terms
Animals, Body Temperature Regulation, Body Weight, Fever, Hypertonic Solutions, Hypothalamus, Interleukin-1, Male, Sodium Chloride, Sucrose, Water-Electrolyte Balance, Signal Transduction, Rats, Sprague-Dawley, Rats

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