scholarly journals Prior viral illness increases heat stroke severity in mice

2020 ◽  
Vol 106 (1) ◽  
pp. 244-257 ◽  
Author(s):  
Shauna M. Dineen ◽  
Jermaine A. Ward ◽  
Lisa R. Leon
Keyword(s):  
Heat Stroke ◽  
Stroke Severity ◽  
Viral Illness

Lack of lymphocytes exacerbate heat stroke severity in male mice through enhanced inflammatory response

2021 ◽  
Vol 101 ◽  
pp. 108206
Author(s):  
Yulong Tan ◽  
Xiaoqian Liu ◽  
Xueting Yu ◽  
Tingting Shen ◽  
Zeze Wang ◽  
...  
Keyword(s):  
Inflammatory Response ◽  
Heat Stroke ◽  
Stroke Severity ◽  
Male Mice

scholarly journals Coagulopathy signature precedes and predicts severity of end-organ heat stroke pathology in a mouse model

2019 ◽  
Author(s):  
Elizabeth A. Proctor ◽  
Shauna M. Dineen ◽  
Stephen C. Van Nostrand ◽  
Madison K. Kuhn ◽  
Christopher D. Barrett ◽  
...  
Keyword(s):  
Body Temperature ◽  
Mouse Model ◽  
Core Body Temperature ◽  
Heat Stroke ◽  
Organ Damage ◽  
Supervised Machine Learning ◽  
Stroke Severity ◽  
Immune Challenge ◽  
Core Body ◽  
D Dimer

AbstractHeat stroke is a life-threatening condition characterized by loss of thermoregulation and severe elevation of core body temperature, which can cause organ failure and damage to the central nervous system. While no definitive test exists to measure heat stroke severity, immune challenge is known to increase heat stroke risk, although the mechanism of this increased risk is unclear. In this study, we used a mouse model of classic heat stroke to test the effect of immune challenge on pathology. Employing multivariate supervised machine learning to identify patterns of molecular and cellular markers associated with heat stroke, we found that prior viral infection simulated with poly I:C injection resulted in heat stroke presenting with high levels of factors indicating coagulopathy. Despite a decreased number of platelets in the blood, platelets are large and non-uniform in size, suggesting younger, more active platelets. Levels of D-dimer and soluble thrombomodulin were increased in more severe heat stroke, and in cases presenting with the highest level of organ damage markers D-dimer levels dropped, indicating potential fibrinolysis-resistant thrombosis. Genes corresponding to immune response, coagulation, hypoxia, and vessel repair were up-regulated in kidneys of heat-challenged animals, and these increases correlated with both viral treatment and distal organ damage while appearing before discernible tissue damage to the kidney itself. We conclude that heat stroke-induced coagulopathy may be a driving mechanistic force in heat stroke pathology, especially when exacerbated by prior infection, and that coagulation markers may serve as an accessible biomarker for heat stroke severity and therapeutic strategies.Key pointsA signature of pro-coagulation markers predicts circadian core body temperature and levels of organ damage in heat strokeChanges in coagulopathy-related gene expression are evidenced before histopathological organ damage

scholarly journals NLRP3 ablation enhances tolerance in heat stroke pathology by inhibiting IL-1β-mediated neuroinflammation

2021 ◽  
Vol 18 (1) ◽  
Author(s):  
Zi-Teng Zhang ◽  
Xiao-Lei Gu ◽  
Xin Zhao ◽  
Xian He ◽  
Hao-Wei Shi ◽  
...  
Keyword(s):  
Heat Tolerance ◽  
Knockout Mice ◽  
Nlrp3 Inflammasome ◽  
Heat Stroke ◽  
Heat Exposure ◽  
Neutralizing Antibody ◽  
Underlying Mechanism ◽  
Stroke Severity ◽  
Inflammasome Activation ◽  
Prior Infection

Abstract Background Patients with prior illness are more vulnerable to heat stroke-induced injury, but the underlying mechanism is unknown. Recent studies suggested that NLRP3 inflammasome played an important role in the pathophysiology of heat stroke. Methods In this study, we used a classic animal heat stroke model. Prior infection was mimicked by using lipopolysaccharide (LPS) or lipoteichoic acid (LTA) injection before heat stroke (LPS/LTA 1 mg/kg). Mice survival analysis curve and core temperature (TC) elevation curve were produced. NLRP3 inflammasome activation was measured by using real-time PCR and Western blot. Mice hypothalamus was dissected and neuroinflammation level was measured. To further demonstrate the role of NLRP3 inflammasome, Nlrp3 knockout mice were used. In addition, IL-1β neutralizing antibody was injected to test potential therapeutic effect on heat stroke. Results Prior infection simulated by LPS/LTA injection resulted in latent inflammation status presented by high levels of cytokines in peripheral serum. However, LPS/LTA failed to cause any change in animal survival rate or body temperature. In the absence of LPS/LTA, heat treatment induced heat stroke and animal death without significant systemic or neuroinflammation. Despite a decreased level of IL-1β in hypothalamus, Nlrp3 knockout mice demonstrated no survival advantage under mere heat exposure. In animals with prior infection, their heat tolerance was severely impaired and NLRP3 inflammasome induced neuroinflammation was detected. The use of Nlrp3 knockout mice enhanced heat tolerance and alleviated heat stroke-induced death by reducing mice hypothalamus IL-1β production with prior infection condition. Furthermore, IL-1β neutralizing antibody injection significantly extended endotoxemic mice survival under heat stroke. Conclusions Based on the above results, NLRP3/IL-1β induced neuroinflammation might be an important mechanistic factor in heat stroke pathology, especially with prior infection. IL-1β may serve as a biomarker for heat stroke severity and potential therapeutic method.

Point-of-care cardiac troponin test accurately predicts heat stroke severity in rats

2015 ◽  
Vol 309 (10) ◽  
pp. R1264-R1272 ◽  
Author(s):  
Gerald N. Audet ◽  
Carrie M. Quinn ◽  
Lisa R. Leon
Keyword(s):  
Cardiac Troponin ◽  
Point Of Care ◽  
Heat Stroke ◽  
Heat Exposure ◽  
Field Tests ◽  
Organ Damage ◽  
Band Intensity ◽  
Health Concern ◽  
Clinical Test ◽  
Stroke Severity

Heat stroke (HS) remains a significant public health concern. Despite the substantial threat posed by HS, there is still no field or clinical test of HS severity. We suggested previously that circulating cardiac troponin (cTnI) could serve as a robust biomarker of HS severity after heating. In the present study, we hypothesized that (cTnI) point-of-care test (ctPOC) could be used to predict severity and organ damage at the onset of HS. Conscious male Fischer 344 rats ( n = 16) continuously monitored for heart rate (HR), blood pressure (BP), and core temperature (Tc) (radiotelemetry) were heated to maximum Tc (Tc,Max) of 41.9 ± 0.1°C and recovered undisturbed for 24 h at an ambient temperature of 20°C. Blood samples were taken at Tc,Max and 24 h after heat via submandibular bleed and analyzed on ctPOC test. POC cTnI band intensity was ranked using a simple four-point scale via two blinded observers and compared with cTnI levels measured by a clinical blood analyzer. Blood was also analyzed for biomarkers of systemic organ damage. HS severity, as previously defined using HR, BP, and recovery Tc profile during heat exposure, correlated strongly with cTnI ( R2 = 0.69) at Tc,Max. POC cTnI band intensity ranking accurately predicted cTnI levels ( R2 = 0.64) and HS severity ( R2 = 0.83). Five markers of systemic organ damage also correlated with ctPOC score (albumin, alanine aminotransferase, blood urea nitrogen, cholesterol, and total bilirubin; R2 > 0.4). This suggests that cTnI POC tests can accurately determine HS severity and could serve as simple, portable, cost-effective HS field tests.

scholarly journals Prior Viral Illness Exacerbates the Severity of Lung Injury in a Mice Heat Stroke Model

2018 ◽  
Vol 32 (S1) ◽  
Author(s):  
Mark l. Plamper ◽  
Shauna M. Dineen ◽  
Michelle A. King ◽  
Lisa R. Leon
Keyword(s):  
Lung Injury ◽  
Heat Stroke ◽  
Stroke Model ◽  
Viral Illness

Cardiovascular and thermoregulatory biomarkers of heat stroke severity in a conscious rat model

2014 ◽  
Vol 117 (9) ◽  
pp. 971-978 ◽  
Author(s):  
Carrie M. Quinn ◽  
Rocio M. Duran ◽  
Gerald N. Audet ◽  
Nisha Charkoudian ◽  
Lisa R. Leon
Keyword(s):  
Troponin I ◽  
Point Of Care ◽  
Multiorgan Failure ◽  
Heat Stroke ◽  
Heat Exposure ◽  
Fold Increase ◽  
Organ Damage ◽  
Stroke Severity ◽  
Conscious Rat ◽  
Novel Biomarkers

Multiorgan failure is a catastrophic consequence of heat stroke (HS) and considered the underlying etiology of mortality. Identifying novel biomarkers capable of predicting the extent of HS-induced organ damage will enhance point-of-care triage and treatment. Conscious male F344 rats ( n = 32) were radiotelemetered for continuous core temperature (Tc), heart rate, and arterial pressure measurement. Twenty-two animals were exposed to ambient temperature of 37°C to a maximum Tc of 41.9 ± 0.1°C. Rats were euthanized at 24 h of recovery for analysis of plasma biomarkers [cardiac troponin I (cTnI), blood urea nitrogen (BUN), alanine aminotransferase (ALT), albumin, glucose] and histology. Tc profiles observed during recovery stratified HS severity into Mild, Moderate, and Severe. Eleven (50%) animals exhibited an acute compensatory hemodynamic response to heat exposure and a monophasic Tc profile consisting of sustained hyperthermia (∼1°C). Five (23%) rats displayed hemodynamic challenge and a biphasic Tc profile with rapid return to baseline followed by rebound hyperthermia. All biomarkers were significantly altered from control values ( P < 0.05). Four (18%) animals exhibited significant hemodynamic compromise during heat and a triphasic profile characterized by rapid cooling to baseline Tc, rebound hyperthermia, and subsequent hypothermia (∼35°C) through 24 h. cTnI showed a 40-fold increase over CON ( P < 0.001) and correlated with BUN ( r = 0.912) consistent with cardiorenal failure. Hypoglycemia correlated with ALT ( r = 0.824) suggestive of liver dysfunction. Histology demonstrated myocardial infarction, renal tubular necrosis, and acute liver necrosis. Two (9%) animals succumbed during HS recovery. This study identified novel biomarkers that predict HS severity and organ damage during acute recovery that could provide clinical significance for identifying key biomarkers of HS pathogenesis.

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