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Updated: Aug 3, 2025

Protocol for Long Duration Whole Body Hyperthermia in Mice
Published on: August 25, 2012
Hyperthermia alters neurobehavior by affecting cell proliferation and neuronal survival in young male rats
Fatih Mete1, Signem Eyuboglu2,3, Ayca Vitrinel4
1Department of Pediatrics, Bagcilar Training and Research Hospital, Istanbul, Turkey.
Insights
Hyperthermia in young rats impairs behavior and motor function by increasing brain cell death and reducing cell proliferation. These findings highlight the critical impact of fever on developing neurological systems.
Area of Science:
- Neuroscience
- Developmental Biology
- Pediatrics
Background:
- Maintaining normal body temperature is vital for fetal and neonatal development.
- Pediatric hyperthermia can lead to neurological damage and disorders.
- Fever is a common pediatric complaint with potential long-term consequences.
Purpose of the Study:
- To investigate the impact of hyperthermia on behavior, neuronal survival, apoptosis, and cell proliferation in young rats.
- To assess neurobehavioral changes and cellular responses to elevated body temperatures.
- To determine the dose-dependent effects of hyperthermia on the developing brain.
Main Methods:
- Young Sprague-Dawley rats were exposed to controlled hyperthermia (39°C and 41°C) or normal temperature (36°C).
- Behavioral tests (open field, elevated-O-maze, grip strength) assessed locomotor activity, anxiety, and motor function.
- Neuronal survival, apoptosis, and cell proliferation were quantified in brain regions including the cortex, hippocampus (DG, CA1), and corpus callosum.
Main Results:
- Hyperthermia induced significant behavioral deficits, including decreased activity, motor function, and increased anxiety, more pronounced at 41°C.
- Neuronal survival was significantly reduced in the dentate gyrus (DG), CA1, and corpus callosum (CC).
- Hyperthermia increased apoptosis in the cortex, DG, and CC, while decreasing cell proliferation in the DG and CC.
Conclusions:
- Hyperthermia causes significant neurobehavioral deficits in developing rats.
- Increased apoptosis and reduced cell proliferation contribute to neuronal damage and functional impairments.
- These findings underscore the critical need to manage fever in pediatric populations to prevent neurological sequelae.
Abstract:
Maintenance of body temperature within physiological range is critical for the fetal and neonatal development. Hyperthermia is one of the most frequently encountered pediatric complaints and may cause neurological disorders due to neuronal injury. In this study, we aimed to investigate the effects of hyperthermia on behavioral alterations, neuronal survival, apoptosis, and cell proliferation in young male Sprague-Dawley rats. Twenty-one 13-day-old rats were randomly divided into three groups (n = 7 per group). Body temperature was increased to 39°C and 41°C in a hyperthermia induction chamber for 30 min, whereas the animals in control group were maintained at 36°C. Twenty-four hours after hyperthermia, animals were subjected to the open field test, elevated-O-maze test, and grip strength test to assess the locomotor activity, anxiety, and motor function. Neuronal survival, apoptosis, and cell proliferation were investigated in cortex, hippocampal dentate gyrus (DG) and CA1 regions, and corpus callosum (CC). Decreased locomotor activity and motor function and increased anxiety were observed in the hyperthermia groups, and these were more pronounced in the 41°C group. Neuronal survival was significantly decreased in DG, CA1, and CC in the hyperthermia groups (**p < 0.01). Apoptosis was significantly induced in cortex, DG, and CC of the animals exposed to heat (*p < 0.05). In addition, cell proliferation positivity decreased significantly only in DG and CC of the animals exposed to heat (*p < 0.05). Our results suggest that neurobehavioral deficits caused by hyperthermia may be due to the increased apoptosis and neuronal cell death and decreased cell proliferation in the brain of postnatal developing rats.
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