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Experimental and Therapeutic Medicine May 2023Chronic fragmented sleep is a very common type of insomnia that affects the daily lives of numerous people around the world. However, its pathogenesis is not very clear...
Chronic fragmented sleep is a very common type of insomnia that affects the daily lives of numerous people around the world. However, its pathogenesis is not very clear and a corresponding rat model has not been reported for this purpose at present. The present study aimed to establish a rat model of chronic insomnia with sleep fragmentation using self-made multiple strings of unstable platforms surrounded by shallow water. During the establishment of the models, changes in body weight and differences in food and water intake in the daytime and at night were acquired. The rat models were assessed using several tests, including the Morris water maze test, pentobarbital sodium-induced sleep, infrared monitoring and electroencephalogram/electromyography during sleep. The expression levels of certain inflammatory factors and orexin A were detected in the serum and brain tissues using ELISAs, immunohistochemistry and immunofluorescence. The expression levels of orexin 1 receptor (orexin 1r) were also detected in the brain. Polysomnography indicated that the model rats were successfully prepared with reduced non-rapid eye movement (non-REM) sleep in the daytime, which was increased at night, and considerably lower REM duration during the day and night. The number of instances of sleep arousals were also increased in the day and at night, and the average duration of each sleep bout was decreased in the daytime. The body weights of the model rats increased at a normal rate. However, the reduction of body weight in the daytime and increased in body weight at night were significantly less than those of the control rats. The daytime food and water consumption of the model rats increased significantly compared with that of the control rats, but was similar to that of the control group at night. The Morris water maze test indicated that the model rats were slow to learn to escape the platforms and performed a lower number of target crossings. The pentobarbital-induced sleep experiment confirmed that the model rats exhibited a longer sleep latency and shorter sleep time. The serum IL-1β, IL-6, TNF-α and orexin A levels of the model rats were significantly increased, whereas their serum IL-10 levels were significantly decreased compared with those of the control rats. The expression levels of IL-1β, IL-6, orexin A and orexin 1r in the brain tissues of the model rats were also significantly increased. In conclusion, these data indicate that learning and memory function, sleep time, arousal times, diurnal and nocturnal body weight changes, food and water intake, and expression levels of the specific inflammatory factors orexin A and orexin 1r were altered in the model rats. This suggests the chronic insomnia rat model with sleep fragmentation was successfully established using multiple strings of unstable platforms surrounded by water.
PubMed: 37114171
DOI: 10.3892/etm.2023.11932 -
Turkish Journal of Medical Sciences Jun 2022Anesthetics are often used in animal experiments to achieve immobilization and relieve pain. However, many anesthetics can alter the dynamics of cardiovascular systems.... (Observational Study)
Observational Study
BACKGROUND
Anesthetics are often used in animal experiments to achieve immobilization and relieve pain. However, many anesthetics can alter the dynamics of cardiovascular systems. We aimed to compare the effects of two frequently used anesthetics agents on heart rate variability (HRV) parameters in mice.
METHODS
This observational study was performed between May and June 2014 in 21 male BALB/c mice aged 16-20 weeks. The animals were divided into three groups: pentobarbital (P), (n = 7); pentobarbital+fentanyl (P+F), (n = 7); and ketamine+xylazine (K+X), (n = 7). Surface electrocardiography (ECG) electrodes were placed in lead II configuration. The tachogram of RR intervals was obtained after R waves were detected using the Pan-Tompkins real-time QRS recognition algorithm. Frequency-domain, time-domain, and nonlinear HRV analyses were performed.
RESULTS
The bradycardia effect was higher in the K+X group (p < 0.01). Time-domain indices were higher in group K+X compared to group P (p < 0.01) and group P+F (p < 0.001). Very low frequency (VLF) power was significantly lower in group K+X compared to group P and group P+F (p < 0.01). Low frequency (LF) power, low frequency/high frequency (LF/HF) ratio, and total power (TP) were higher in group K+X compared to group P (p < 0.01) and group P+F (p < 0.001). The detrended fluctuation analysis short-term parameter (DFAα1 ) was significantly higher in group K+X compared to group P+F (p < 0.05) and the long-term parameter (DFAα2 ) was lower in group K+X compared to group P (p < 0.05). Standard deviations SD1 and SD2 were higher in group K+X compared to group P (p < 0.001) and group P+F (p < 0.001), SD2/SD1 ratio was lower in group K+X compared to group P (p < 0.05) and group P+F (p < 0.05). Entropy measures did not differ between groups.
DISCUSSION
HRV analyses, including nonlinear methods, indicated that a K+X combination reduces imbalance and disorder in the regulation of the autonomic nervous system (ANS) in comparison to both P and the P+F combination.
Topics: Male; Mice; Animals; Heart Rate; Xylazine; Ketamine; Pentobarbital; Electrocardiography; Anesthesia; Anesthetics; Fentanyl
PubMed: 36326322
DOI: 10.55730/1300-0144.5383 -
International Journal of Experimental... Feb 2021This study aims to compare the influence of different anaesthesia methods on the mechanisms involved in the development of hepatoblastoma (HB). HB rabbit models were...
This study aims to compare the influence of different anaesthesia methods on the mechanisms involved in the development of hepatoblastoma (HB). HB rabbit models were constructed and divided into three groups: disoprofol, pentobarbital sodium and HB groups. After anaesthesia, rabbit blood was collected from the tail vein. Haematological analysis (platelets) and an ELISA was used to measure the thrombopoietin (TPO) and 5-hydroxytryptamine (5-HT). Flow cytometry was used to determine expression of P-selectin and PAF. The expression of 5-HTR2B, PCNA, vWF, P70s6k, 4E-BP1, mTOR and FRAP was determined in the tumour itself or in vascular tissues obtained from the rabbits. The platelet content in the disoprofol group. The content or expression of TPO, 5-HT, P-selectin, PAF, 5-HTR2B, PCNA, vWF, P70s6k, 4E-BP1, mTOR and FRAP was significantly higher in the disoprofol group compared to pentobarbital sodium and HB groups. Expression of these molecules was much higher in the pentobarbital sodium group compared with the HB group. These findings suggest that disoprofol anaesthesia can promote HB development via the mTOR/p70S6K1 and FRAP signalling pathway.
Topics: Animals; Hepatoblastoma; Hypnotics and Sedatives; Liver Neoplasms; Pentobarbital; Platelet Activation; Propofol; Rabbits; Signal Transduction
PubMed: 33410572
DOI: 10.1111/iep.12378 -
International Journal of Surgery Case... 2020Intracranial hypertension that is not responsive to other therapies can be managed through the use of a barbiturate induced coma. Although potentially effective, there...
INTRODUCTION
Intracranial hypertension that is not responsive to other therapies can be managed through the use of a barbiturate induced coma. Although potentially effective, there are known complications associated with this treatment, and as such it is typically reserved for the most severe cases. One such sequela of barbiturate induced coma therapy is refractory hypokalemia and subsequent rebound hyperkalemia.
PRESENTATION OF CASE
This case report discusses a patient who experienced hypokalemia during pentobarbital induced coma for unmanageable elevations in intracranial pressure and was treated conservatively to avoid rebound hyperkalemia depicting successful deployment of permissive hypokalemia.
DISCUSSION
It is vital that clinicians understand the possible adverse effects associated with barbiturate induced coma therapy, and that a careful balance be struck between hypokalemia and potassium supplementation to avoid rebound hyperkalemia.
CONCLUSION
Given that the risk of rebound hyperkalemia is of significant concern in patients who experience hypokalemia on barbiturate induced coma therapy, permissive hypokalemia can be a viable treatment option achieved by lowering the potassium replacement target threshold in such patients.
PubMed: 32492644
DOI: 10.1016/j.ijscr.2020.05.032 -
Journal of Ethnopharmacology Feb 2023Lavender (Lavandula angustifolia Mill.) essential oil is renowned for its use in the treatment of insomnia and mental disorder diseases in folk medicine. Previous...
ETHNOPHARMACOLOGICAL RELEVANCE
Lavender (Lavandula angustifolia Mill.) essential oil is renowned for its use in the treatment of insomnia and mental disorder diseases in folk medicine. Previous pharmacological studies have also shown that lavender essential oil displays sedative and hypnotic activities. However, the active ingredients and mechanism of lavender essential oil for sleep-improving effect remain unclear.
AIM OF THE STUDY
This study investigates whether inhalation of different fractions of lavender essential oil can attenuate the sleep disturbances induced by combined anxiety and caffeine and explores the underlying mechanisms.
MATERIALS AND METHODS
Molecular distillation was applied to separate lavender essential oil into fractions containing different chemical components, and GC-MS was used to analyze the volatile compounds of lavender essential oil and its fractions. The elevated plus maze test, pentobarbital-induced sleep test, and neurotransmitters enzyme-linked immunosorbent assay were conducted to evaluate the anxiolytic and hypnotic effects of lavender essential oil and its fractions on mice suffering from sleep disorders.
RESULTS
The results of behavioral tests indicated that lavender essential oil and its fractions (3%, v/v) exerted an ameliorating effect on sleep disturbances induced by anxiety and caffeine. The light fraction and heavy fractions exhibited complementary chemical composition, with the former enriched in linalool and trans-β-ocimene and the latter in linalyl acetate, lavandulyl acetate, trans-caryophyllene, etc. The light fraction contributed more to sleep maintenance, and the heavy fraction performed better at sleep initiation. The neurobiological parameters elucidated that the mechanism of lavender essential oil for sleep-improving was multifaceted, related to the GABAergic system, cholinergic system, histaminergic system, and monoamines in the limbic system. The heavy fraction shared a similar mechanism with the lavender essential oil, while the light fraction did not actively participate in the cholinergic system, histaminergic system, and dopaminergic system.
CONCLUSION
Taken together, our results demonstrated that different fractions of lavender essential oil played different roles in ameliorating sleep disorders, and this may be credited to their compositional differences and the complicated interactions with the central nervous system. The results are informative for future investigations on the molecular level mechanisms and provide guidance for appropriate applications of lavender essential oil.
Topics: Animals; Mice; Lavandula; Caffeine; Oils, Volatile; Plant Oils; Anxiety; Sleep Initiation and Maintenance Disorders; Hypnotics and Sedatives; Cholinergic Agents
PubMed: 36309115
DOI: 10.1016/j.jep.2022.115868 -
PloS One 2020Microglia, the resident immune cells of the brain, are highly ramified and motile and their morphology is strongly linked to their function. Microglia constantly monitor...
Microglia, the resident immune cells of the brain, are highly ramified and motile and their morphology is strongly linked to their function. Microglia constantly monitor the brain parenchyma and are crucial for maintaining brain homeostasis and fine-tuning neuronal networks. Besides affecting neurons, anesthetics may have wide-ranging effects mediated by non-neuronal cells and in particular microglia. We thus examined the effect of two commonly used anesthetic agents, ketamine/xylazine and barbiturates, on microglial motility and morphology. A combination of two-photon in vivo imaging and electroencephalography (EEG) recordings in unanesthetized and anesthetized mice as well as automated analysis of ex vivo sections were used to assess morphology and dynamics of microglia. We found that administration of ketamine/xylazine and pentobarbital anesthesia resulted in quite distinct EEG profiles. Both anesthetics reduced microglial motility, but only ketamine/xylazine administration led to reduction of microglial complexity in vivo. The change of cellular dynamics in vivo was associated with a region-dependent reduction of several features of microglial cells ex vivo, such as the complexity index and the ramification length, whereas thiopental altered the size of the cytoplasm. Our results show that anesthetics have considerable effects on neuronal activity and microglial morphodynamics and that barbiturates may be a preferred anesthetic agent for the study of microglial morphology. These findings will undoubtedly raise compelling questions about the functional relevance of anesthetics on microglial cells in neuronal physiology and anesthesia-induced neurotoxicity.
Topics: Anesthetics; Animals; Cell Movement; GABA Modulators; Ketamine; Male; Mice; Mice, Transgenic; Microglia; Pentobarbital; Receptors, N-Methyl-D-Aspartate; Thiopental; Xylazine
PubMed: 32760073
DOI: 10.1371/journal.pone.0236594 -
Biomedicine & Pharmacotherapy =... Feb 2022Treatment of sleep disorders promotes the long-term use of commercially available sleep inducers that have several adverse effects, including addiction, systemic...
Treatment of sleep disorders promotes the long-term use of commercially available sleep inducers that have several adverse effects, including addiction, systemic fatigue, weakness, loss of concentration, headache, and digestive problems. Therefore, we aimed to limit these adverse effects by investigating a natural product, the extract of the Hibiscus syriacus Linnaeus flower (HSF), as an alternative treatment. In the electric footshock model, we measured anxiety and assessed the degree of sleep improvement after administering HSF extract. In the restraint model, we studied the sleep rate using PiezoSleep, a noninvasive assessment system. In the pentobarbital model, we measured sleep improvement and changes in sleep-related factors. Our first model confirmed the desirable effects of HSF extract and its active constituent, saponarin, on anxiolysis and Wake times. HSF extract also increased REM sleep time. Furthermore, HSF extract and saponarin increased the expression of cortical GABA receptor α1 (GABAAR α1) and c-Fos in the ventrolateral preoptic nucleus (VLPO). In the second model, HSF extract and saponarin restored the sleep rate and the sleep bout duration. In the third model, HSF extract and saponarin increased sleep maintenance time. Moreover, HSF extract and saponarin increased cortical cholecystokinin (CCK) mRNA levels and the expression of VLPO c-Fos. HSF extract also increased GABAAR α1 mRNA level. Our results suggest that HSF extract and saponarin are effective in maintaining sleep and may be used as a novel treatment for sleep disorder. Eventually, we hope to introduce HSF and saponarin as a clinical treatment for sleep disorders in humans.
Topics: Animals; Apigenin; Cerebral Cortex; Corticosterone; Disease Models, Animal; Electroencephalography; Glucosides; Hibiscus; Male; Mice, Inbred C57BL; Mice, Inbred ICR; Pentobarbital; Plant Extracts; Preoptic Area; Proto-Oncogene Proteins c-fos; Rats, Sprague-Dawley; Receptors, GABA-A; Sleep; Sleep Aids, Pharmaceutical; Sleep Wake Disorders; Stress, Psychological; Mice; Rats
PubMed: 34915415
DOI: 10.1016/j.biopha.2021.112301 -
RSC Advances Feb 2021The Shenque acupoint is located in the umbilicus of the human body. In the human body meridians, the Shenque acupoint can regulate body functions. The Shenque acupoint...
The Shenque acupoint is located in the umbilicus of the human body. In the human body meridians, the Shenque acupoint can regulate body functions. The Shenque acupoint was one of the important acupuncture acupoints for the treatment of insomnia. However, the effect of linalool applied at the Shenque acupoint to improve sleep was unknown. This study explored the hypnotic and sedative effects of the main component of lavender, linalool, on the Shenque acupoint of mice and rats. The effects on the sleep latency and sleep duration were studied with the supra-threshold dose of pentobarbital sodium, and the effects on the sleep rate were studied with the sub-threshold dose of pentobarbital sodium. In order to further study the feasibility and superiority of linalool administered at the Shenque acupoint, a pharmacokinetic study was carried out. The pharmacodynamic results showed that the mice and rats treated with linalool at Shenque had the highest sleep rate, the shortest sleep latency, and the longest sleep duration compared with other groups. The and of the LS were longer than those of the LO, and had the characteristics of sustained release. The relative bioavailability of LS was 323.0 ± 31.66%. This showed that the combination of linalool and the Shenque acupoint had greater medicinal effects. This development will provide a new direction for improving sleep.
PubMed: 35423146
DOI: 10.1039/d0ra09751a -
Drug Design, Development and Therapy 2020In this study, we investigated the protective effects and mechanism of action of echinacoside (ECH) from cistanche tubulosa extract in cardiomyocytes of diabetic mice.
PURPOSE
In this study, we investigated the protective effects and mechanism of action of echinacoside (ECH) from cistanche tubulosa extract in cardiomyocytes of diabetic mice.
METHODS
Twenty healthy male mice aged 8 weeks were randomly divided into +ECH (n=10, ECH, 300 mg/(kg/d)), (n=10, saline), and control groups (n=9). Mice were monitored weekly for diet and activity. Mice were injected with 2% of pentobarbital sodium in week 10 and executed. Weight and free blood glucose (FBG) were measured weekly. Echocardiographs were used to detect cardiac function. HE staining, Sudan II staining, Masson's trichrome staining and Tunel assays were used to evaluate myocardial tissue pathological changes, collagen fiber deposition, lipid accumulation and apoptosis rates in cardiomyocytes, respectively. Western blot and RT-PCR analysis were used to detect the expression of components of the PPAR-α/M-CPT-1 and p53/p38MAPK signaling axis.
RESULTS
Compared to mice, ECH groups showed lower blood glucose and lipid levels. Deterioration in cardiac function was also delayed following ECH treatment. Histopathological analysis showed that ECH significantly improved myocardial tissue in mice, including reduced intercellular spaces, regular arrangements, improved extracellular matrix deposition, and reduced lipid accumulation. ECH also significantly reduced oxidative stress levels in myocardial tissue in mice. Moreover, ECH inhibited PPAR-α/M-CPT-1 signaling, downregulated CD36, and upregulated glucose transporter type 4 (GLUT-4) expression in mouse models of DCM. ECH also inhibited p53/p38MAPK signaling, downregulated caspase-3 and caspase-8, and upregulated Bcl-2/Bax in mouse models of DCM.
CONCLUSION
ECH displays protective effects in DCM, including the inhibition of cardiac apoptosis and oxidative stress, and improved lipid metabolism in cardiomyocytes. ECH also inhibits cardiac apoptosis through its regulation of p53/p38MAPK signaling, and prevents lipid accumulation through suppression of the PPAR-α/M-CPT-1 signaling axis.
Topics: Animals; Blood Glucose; Diabetes Mellitus, Experimental; Diabetic Cardiomyopathies; Glycosides; Lipids; Male; Mice; Mice, Inbred C57BL; Mice, Obese; Oxidative Stress; Protective Agents
PubMed: 33376302
DOI: 10.2147/DDDT.S276972 -
Current Research in Toxicology 2023This study evaluated nickel and aluminium-induced neurotoxicity, as a binary metal mixture. Twenty-eight male Sprague Dawley albino rats were weight-matched and divided...
Nickel and aluminium mixture elicit memory impairment by activation of oxidative stress, COX-2, and diminution of AChE, BDNF and NGF levels in cerebral cortex and hippocampus of male albino rats.
This study evaluated nickel and aluminium-induced neurotoxicity, as a binary metal mixture. Twenty-eight male Sprague Dawley albino rats were weight-matched and divided into four groups. Group 1 (control) received deionized water. Group 2 and 3 received Aluminium (1 mg/kg) and Nickel (0.2 mg/kg) respectively, while Group 4 received Ni and Al mixture HMM three times a week orally for 90 days. Barnes maze tests was performed. Rats were sacrificed under pentobarbital anaesthesia, cerebral cortex and hippocampus were separated, and metal levels were measured using Atomic Absorption Spectroscopy (AAS). Malondialdehyde (MDA), catalase (CAT), glutathione content (GSH), superoxide dismutase (SOD), glutathione peroxidase (GPx), Brain Derived Neurotrophic Factor (BDNF), Nerve growth factor NGF, -oxygenase COX-2 and Acetylcholinesterase (AChE) were assayed using ELISA kits. Ni/Al binary mixture exposed rats showed a shorter latency period (though not significant) of 3.21 ± 1.40 s in comparison to 3.77 ± 1.11 (Ni only) and 3.99 ± 1.16(Al only). Ni/Al mixture gp had the lowest levels of Mg in both the hippocampus and frontal cortex when compared with the individual metals. In the hippocampus Al only exposed rats significantly showed p < 0.05 higher iron and Ca levels in comparison to Ni/Al mixture. Al alone significantly showed p < 0.05 lower levels of Fe but higher Ca than the Ni/Al mixture group. Exposure to Al only showed lower levels of BDNF in comparison to Ni/Al combination, whereas Ni/Al mixture gp had lower levels of NGF in comparison to the individual metals in the hippocampus. In the frontal cortex Ni only, group showed significantly lower BDNF in comparison to Ni/Al mixture whereas the mixture showed significantly lower NGF when compared with Al only group. There were higher levels of COX-2 in the Ni/Al mixture than individual metal treated rats in both hippocampus and frontal cortex. AChE levels in the Ni/Al mixture group was higher than Ni or Al only gps in the hippocampus whereas in the frontal cortex, Ni/Al exposed rats showed significantly lower AChE levels in comparison to Al only group. Ni, Al and Ni/Al mixture exhibited memory impairment by activation of oxidative stress, COX-2, and diminution of AChE, BDNF and NGF levels in cerebral cortex and hippocampus. The BDNF-COX-2 AChE signalling pathway may be involved in the neurotoxicity of Ni and Al.
PubMed: 37841055
DOI: 10.1016/j.crtox.2023.100129