Interleukin-1 receptor antagonist attenuates the heat stroke-induced neuronal damage by reducing the cerebral ischemia in rats

doi:10.1016/0361-9230(95)00046-H

Brain Research Bulletin

Volume 37, Issue 6, 1995, Pages 595-598

https://doi.org/10.1016/0361-9230(95)00046-H Get rights and content

Abstract

The effects of Interleukin-1 receptor antagonist (IL-Ira) on both local cerebral blood flow and neuronal damage of the hypothalamus, corpus striatum, cortex or thalamus were assessed in rats with heat stroke. Heat stroke was induced by exposing the urethane-anesthetized rats to a high ambient temperature (42°C). Damage to the hypothalamus, corpus striatum, cortex or thalamus was scored on a scale of zero to three modified from the grading system of Pulsinelli and colleagues in which: 0 = normal, l = few neurons damaged, 2 = many neurons damaged, and 3 = all neurons damaged. During the onset of heat stroke, as compared to those of normothermia controls, the heat stroke rats displayed a higher value of colonic temperature or neuronal damage score, as well as a lower value of local cerebral blood flow or mean arterial blood pressure. In addition, compared to those of normotherrnic, control rats, the heat stroke rats had increased Interleukin-1 and tumor necroting factor production in the diencephalon, brain stem and cortex. The heat stroke-induced neuronal damage and diminished local cerebral blood flow in different brain structures, as well as the systemic hypotenston, were attenuated in animals pretreated with IL-1ra (200 μg/kg, iv) 30 min before the onset of heat stroke. The results Indicate that IL-1ra attlenuates the heat stroke-induced cerebral neuronal damage by reducing cerebral Ischemia in rats.

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The results are consistent with the previous studies which showed that oxidative stress mediated brain damage occurred during heat stroke in rats [53,57]. Previous studies have reported that heat-stroke model of rats were associated with cerebral ischemia, increase in the level of interleukin-1β and glutamate as well as dopamine overload in the brain [5,58–61]. These factors are known to increase free radical production under heat exposure [62,63].
Heat exposure is an environmental stress that causes diverse heat related pathophysiological changes under extreme conditions. The brain including hippocampal region which is associated with learning and memory is significantly affected by heat stress resulting in memory impairment. However, the effect of heat on the spatial memory remains unclear. The present study aimed to explore the effect of heat stress on hippocampus and spatial memory in rats. Rat model of acute heat stress was used which was divided into two groups, viz. moderate heat stress (MHS) and severe heat stress (SHS). Redox parameters evaluation revealed that MHS and SHS exposure markedly increase the production of malondialdehyde (MDA), oxidised glutathione (GSSG), reactive oxidative species (ROS), protein oxidation level and decrease the reduced glutathione (GSH) levels in the hippocampal tissue. Furthermore, Cresyl Violet (CV) staining of hippocampal region showed higher pyknosis in rats exposed to SHS. Pronounced increase of caspase3 expression and Fluoro Jade-C (FJ-C) positive cells were observed in SHS resulting in neuronal injury and apoptosis in CA3 region of hippocampus culminating in spatial memory deficit. Our data also suggest that heat stress induces phospho Extracellular signal-regulated kinases (pERK)1/2 activation induced by Brain-derived neurotrophic factor (BDNF) leading to further activation of phospho cAMP-response element binding protein (pCREB) under MHS. However, during SHS, BDNF and pCREB expression were completely dysregulated and not sufficient to rescue cognitive decline in rats. In conclusion, SHS induces pathological alterations that include oxidative damage and apoptosis of hippocampal neurons, disturbing BDNF/ERK1/2/CREB axis that may affect spatial memory.
Stress biomarkers and proteomics alteration to thermal stress in ruminants: A review
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Heat stress may adversely affect physiochemical and immune responses of livestock and alter biological functions. The comfort or thermoneutral zone for livestock, which has long been a subject of research, mainly depends on species, breed, and health. Heat stress is associated with impaired livestock productivity due to reductions in feed intake, growth rates and immunity and changes in blood constituents and biological pathways. In ruminants, elevated temperatures have deleterious consequences on protein synthesis. Exposure of ruminant animals to elevated temperatures may induce release of heat shock proteins (HSPs); HSPs usually enter the blood circulation during tissue damage and causes cell necrosis or death. Additionally, hyperthermia is associated with augmented production of cellular reactive oxygen species (ROS), which cause protein degradation and further decrease protein synthesis by preventing protein translation. Moreover, it has been suggested that high environmental temperatures lead to increased inflammatory signalling in tissues via activation of the nuclear factor kappa B (NF-κB) and tumor necrosis factor alpha (TNF-α) pathways as well as via alteration of skin colour gene (melanocortin 1 receptor (MC1R) and premelanosome protein (PMEL)) expression. Previous proteomics analyses have suggested that heat stress can reduce adenosine triphosphate (ATP) synthesis, alter gluconeogenesis precursor supply, and induce lipid accumulation in the liver with subsequent disturbance of liver structure. This review focuses on the scientific evidence regarding the impact of heat stress on immune and inflammatory responses, antioxidant status, stress biomarkers, skin colour gene (PMEL and MC1R) expression and proteomic profiles in ruminants.
Heat shock protein 72 may improve hypotension by increasing cardiac mechanical efficiency and arterial elastance in heatstroke rats
2016, International Journal of Cardiology
Citation Excerpt :
Interleukin-1 receptor mechanism was reported to be involved in development of arterial hypotension in rat heatstroke [30]. The arterial hypotension associated with heatstroke could be attenuated by pretreatment of animals with an antagonist of interleukin-1 receptors [31,32]. It is not known whether HSP 72-mediated MHP improves heatstroke-induced arterial hypotension by affecting interleukin-1 receptor-mediated left ventricular performance.
We attempted to test the hypothesis that preinduction of heat shock protein (HSP) 72 in the heart would improve left ventricular performance in rat heatstroke.
Cardiac expression of HSP 72 was quantitatively evaluated by western blot analysis in rats 0 h, 12 h, or 72 h after mild heat preconditioning (MHP; 43 °C for 30 min). They were subjected to severe heat stress (SHS; 43 °C for 70 min) to induce heatstroke. A 1.2 F catheter-tip pressure transducer was inserted into the left ventricle of these group rats under general anesthesia to record hemodynamic in the closed chest with a pressure–volume loop module data recording and analysis system.
At the time point of heatstroke onset, compared with normothermic controls, group rats with 12 h post-MHP had significantly increased cardiac HSP 72, decreased hyperthermia, decreased hypotension, decreased bradycardia, increased end-systolic pressure, increased end-diastolic pressure, increased stroke volume, decreased end-systolic volume, decreased end-diastolic pressure, increased cardiac output, increased ejection fraction, increased stroke work, increased arterial elastance, and decreased time constant of fall in ventricular pressure by Glantz-methods. With the loss of cardiac HSP 72 expression observed at 72 h in post-MHP group rats, an insignificant protection against left ventricular performance was observed.
Preinduction of cardiac HSP 72 may improve hypotension in heatstroke rats by increasing both cardiac mechanical efficiency and arterial elastance.
Acute brief heat stress in late gestation alters neonatal calf innate immune functions<sup>1</sup>
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Heat stress, as one of the environmental stressors affecting the dairy industry, compromises the cow milk production, immune function, and reproductive system. However, few studies have looked at how prenatal heat stress (HS) affects the offspring. The objective of this study was to evaluate the effect of HS during late gestation on calf immunity. Calves were born to cows exposed to evaporative cooling (CT) or HS (cyclic 23–35°C) for 1 wk at 3 wk before calving. Both bull and heifer calves (CT, n = 10; HS, n = 10) were housed in similar environmental temperatures after birth. Both CT and HS calves received 3.78 L of pooled colostrum within 12 h after birth and were fed the same diet throughout the study. In addition to tumor necrosis factor α, IL-1β, IL-1 receptor antagonist (IL-1RA), and toll-like receptor (TLR)2, and TLR4 mRNA expression, the expression of CD14⁺ and CD18⁺ cells, and DEC205⁺ dendritic cells were determined in whole blood samples at d 0, 3, 7, 14, 21, and 28. The neutrophil to lymphocyte ratio, differential cell counts, and the hematocrit were also determined. During late gestation, the HS cows had greater respiration rates, rectal temperatures, and tended to spend more time standing compared with the CT cows. The HS calves had less expression of tumor necrosis factor-α and TLR2 and greater levels of IL-1β, IL-1RA, and TLR4 compared with CT calves. The HS calves also had a greater percentage of CD18⁺ cells compared with the CT calves. Additionally, a greater percentage of neutrophils and lesser percentage of lymphocytes were in the HS calves compared with the CT calves. The results indicate that biomarkers of calves’ immunity are affected in the first several weeks after birth by HS in the dam during late gestation.
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Liver injury is a common complication of heat stroke (HS), and often constitutes a direct cause for patient death. The cellular and molecular mechanism underlying HS-induced liver injury remains unclear. Recent evidence indicates that inflammasome plays an important role in mediating sterile inflammation triggered by tissue damage. Using a rat HS model, we identified a novel mechanism by which inflammasome-dependent interleukin-1β (IL-1β) activation and hepatocyte pyroptosis mediate HS-induced liver injury.
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These findings demonstrate an important role of HMGB1 in mediating inflammasome activation in the development of liver injury following HS, and suggest that targeting inflammasome may represent a novel therapeutic strategy to limit cell death and prevent liver failure after HS.
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2014, Physiology and Behavior
Acute stress increases the expression of cytokines and other inflammatory-related factors in the CNS, plasma, and endocrine glands, and activation of inflammatory signaling pathways within the hypothalamic–pituitary–adrenal (HPA) axis may play a key role in later stress sensitization. In addition to providing a summary of stress effects on neuroimmune changes within the CNS, we present a series of experiments that characterize stress effects on members of the interleukin-1β (IL-1) super-family and other inflammatory-related genes in key structures comprising the HPA axis (PVN, pituitary and adrenal glands), followed by a series of experiments examining the impact of exogenous hormone administration (CRH and ACTH) and dexamethasone on the expression of inflammatory-related genes in adult male Sprague–Dawley rats. The results demonstrated robust, time-dependent, and asynchronous expression patterns for IL-1 and IL-1R2 in the PVN, with substantial increases in IL-6 and COX-2 in the adrenal glands emerging as key findings. The effects of exogenous CRH and ACTH were predominantly isolated within the adrenals. Finally, pretreatment with dexamethasone severely blunted neuroimmune changes in the adrenal glands, but not in the PVN. These findings provide novel insight into the relationship between stress, the expression of inflammatory signaling factors within key structures comprising the HPA axis, and their interaction with HPA hormones, and provide a foundation for better understanding the role of cytokines as modulators of hypothalamic, pituitary and adrenal sensitivity.

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ArticleInterleukin-1 receptor antagonist attenuates the heat stroke-induced neuronal damage by reducing the cerebral ischemia in rats

Abstract

Cell Immunol.

Neurosci. Lett.

Heat stroke and endotoxemia in rabbits

Increased survival in experimental dog heat stroke after reduction of gut flora

Aviat. Space Environ. Med.

Rabbit IL-1 cloning, expression, biologic properties, and transcription during endoto-x emia

J. Immunol.

Cerebral ischemia is the main cause for the heat stroke syndrome in rabbits

Experientia

Article
Interleukin-1 receptor antagonist attenuates the heat stroke-induced neuronal damage by reducing the cerebral ischemia in rats