The Effects of Intraoperative Hypothermia on Postoperative Cognitive Function in the Rat Hippocampus and Its Possible Mechanisms

Xu, Guangyan; Li, Tianjia; Huang, Yuguang

doi:10.3390/brainsci12010096

Cited by 10 publications

(7 citation statements)

References 58 publications

(66 reference statements)

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“…In other words, the precise protective mechanisms are not yet fully understood. As for our study, the memory decline was observed after the inadvertent intraoperative hypothermia both in clinical practice and animal experiment [ 4 , 42 , 45 , 46 ]. In regard to cerebral blood flow, the therapeutic hypothermia also induced reduction in post-ischemic hyperperfusion and sustained hypoperfusion [ 72 ].…”

Section: Discussionmentioning

confidence: 81%

“…Clinical investigations and rat maze experiments both demonstrated that intraoperative hypothermia could lead to memory decline [ 4 , 42 ]. As memory is generated in the hippocampus, intraoperative hypothermia may negatively impact the hippocampus.…”

Section: Discussionmentioning

confidence: 99%

“…In this study, the expression of Arc in the CA1 region was decreased by intraoperative hypothermia ( Figure 4 ). In addition, our maze experiment showed that reducing Arc expression in the CA1 region could attenuate the spatial memory of rats [ 42 ]. The low expression of Arc is associated with memory decline in different neurological diseases.…”

Section: Discussionmentioning

confidence: 99%

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Intraoperative Hypothermia Induces Vascular Dysfunction in the CA1 Region of Rat Hippocampus

et al. 2022

Brain Sciences

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Intraoperative hypothermia is very common and leads to memory decline. The hippocampus is responsible for memory formation. As a functional core area, the cornu ammonis 1 (CA1) region of the hippocampus contains abundant blood vessels and is susceptible to ischemia. The aim of the study was to explore vascular function and neuronal state in the CA1 region of rats undergoing intraoperative hypothermia. The neuronal morphological change and activity-regulated cytoskeleton-associated protein (Arc) expression were evaluated by haematoxylin-eosin staining and immunofluorescence respectively. Histology and immunohistochemistry were used to assess vascular function. Results showed that intraoperative hypothermia inhibited the expression of vascular endothelial growth factor and endothelial nitric oxide synthase, and caused reactive oxygen species accumulation. Additionally, the phenotype of vascular smooth muscle cells was transformed from contractile to synthetic, showing a decrease in smooth muscle myosin heavy chain and an increase in osteopontin. Ultimately, vascular dysfunction caused neuronal pyknosis in the CA1 region and reduced memory-related Arc expression. In conclusion, neuronal disorder in the CA1 region was caused by intraoperative hypothermia-related vascular dysfunction. This study could provide a novel understanding of the effect of intraoperative hypothermia in the hippocampus, which might identify a new research target and treatment strategy.

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Section: Discussionmentioning

confidence: 81%

Section: Discussionmentioning

confidence: 99%

Section: Discussionmentioning

confidence: 99%

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Intraoperative Hypothermia Induces Vascular Dysfunction in the CA1 Region of Rat Hippocampus

et al. 2022

Brain Sciences

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“…In the previously mentioned study, animals regained a normal core body temperature after 90 min after the 15 min forced swim in 24 ± 1°C cold water [ 16 ]. The physical consequences of hypothermia should not be overlooked: Several studies showed detrimental effects of hypothermia on spatial working memory and damage in the hippocampus [ 42 , 43 ]. A possible refinement of the forced swim test might therefore be using warmer water to prevent hypothermia, which is only rarely done so far [ 44 , 45 ].…”

Section: Discussionmentioning

confidence: 99%

Evidence-based severity assessment of the forced swim test in the rat

Becker,

Mallien,

Pfeiffer

et al. 2023

PLoS ONE

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The forced swim test (FST) is a traditional assay, which has been used for more than 40 years to assess antidepressant effects of novel drug candidates. In recent years, a debate about the test has focused on the assumption that the FST is highly aversive and burdening for the animals because of the earlier anthropomorphic interpretation and designation as a "behavioral despair test". The Directive 2010/63/EU and the German Animal Welfare law require a prospective severity classification of the planned experimental procedures. Still, an objective examination of the animals’ burden in this test has not been performed yet. To fill this gap, we conducted an evidence-based severity assessment of the forced swim test in rats according to a ’standard protocol’ with a water temperature of 25°C. We examined parameters representing the physiological and the affective state, and natural as well as locomotion-associated behaviors in three separate experiments to reflect as many dimensions as possible of the animal’s condition in the test. Hypothermia was the only effect observed in all animals exposed to the FST when using this standard protocol. Additional adverse effects on body weight, food consumption, and fecal corticosterone metabolite concentrations occurred in response to administration of the antidepressant imipramine, which is frequently used as positive control when testing for antidepressant effects of new substances. We conclude that this version of the FST itself is less severe for the animals than assumed, and we suggest a severity classification of ’moderate’ because of the acute and short-lasting effects of hypothermia. To refine the FST according to the 3Rs, we encourage confirming the predictive validity in warmer water temperatures to allow the rats to maintain physiological body temperature.

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“…The MWM test is a reliable test correlated with hippocampal synaptic plasticity (Vorhees & Williams, 2006). Studies have shown that intraoperative .96 e,a,c,h,j 0.15 6 14 37.56 f,a,c,d,e,g,h,i,j 0.52 7 14 37.63 g,a,c,d,e,f,g,i,j 0.11 8 14 37.61 h,a,cd,e,f,g,i,j 0.18 9 14 37.52 i,a,d,f,g,h 0.12 10 14 37.84 j,a,c,e,f,g,h 0.17 hypothermia negatively affects spatial memory (Xu et al, 2022). The hippocampus is a brain region that is responsible for spatial memory functions (Bellmund et al, 2018) and is quite responsive to stress (Eichenbaum, 2000;O'Keefe & Nadel, 1979;Scoville & Milner, 1957).…”

Section: Discussionmentioning

confidence: 99%

Effects of waiting time between trials and water temperature on cognitive functions, body temperature and body weight in rats in Morris water maze

Oran

Yıldız

TEMİZYÜREK>

et al. 2022

Journal of Istanbul Veterinary Sciences

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The Morris water maze (MWM) is a widely used test among neurobiologists to measure spatial memory. The implementation of this test carries the risk of hypothermia periods in animals. The level of hypothermia may affect age-related memory processes as a significant factor. The occurrence of hypothermia throughout the MWM protocol should be better understood as hypothermia may impair memory performance. Ensuring the standardization of the experiments and minimizing side effects require a detailed examination of the hypothermia-related processes. Our study aims to replicate and extend the data of previous studies in terms of determining the possible species-specific variations and provide data for reorganizing the time intervals. In this study, rats (Wistar Hannover) were used and grouped according to the differences in the inter-trial interval (ITI) (30-s and 13-min) and water temperatures (20 °C and 24 °C). The effects of ITI and water temperature on probe performance were analysed statistically (mixed two-way ANOVA). Results showed that the 13 minute waiting group of animals performed statistically better in the MWM probe phase compared to the 30 second waiting group. The prolongation of ITI between the tests was found to have a positive impact on the memory performance. Longer ITI should be preferred instead of the frequently used 30-60 second test intervals. Thus, animals will be exposed to less stress and more reliable results can be obtained, also possible side effects of hypothermia can be minimized while performing the MWM test.

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The Effects of Intraoperative Hypothermia on Postoperative Cognitive Function in the Rat Hippocampus and Its Possible Mechanisms

Cited by 10 publications

References 58 publications

Intraoperative Hypothermia Induces Vascular Dysfunction in the CA1 Region of Rat Hippocampus

Intraoperative Hypothermia Induces Vascular Dysfunction in the CA1 Region of Rat Hippocampus

Evidence-based severity assessment of the forced swim test in the rat

Effects of waiting time between trials and water temperature on cognitive functions, body temperature and body weight in rats in Morris water maze

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