Manifestations In Rats Research Articles

Systemic inflammation in Aβ1-40-induced Alzheimer’s disease model: New translational opportunities

Alzheimer disease (AD) is the most frequent cause of dementia, and the most common neurodegenerative disease, which is characterized by memory impairment, neuronal death, and synaptic loss in the hippocampus. Sporadic late-onset AD, which accounts for over 95 % of disease cases, is a multifactorial pathology with complex etiology and pathogenesis. Nowadays, neuroinflammation is considered the third most important component of AD pathogenesis in addition to amyloid peptide generation and deposition. Neuroinflammation is associated with the impairment of blood–brain barrier and leakage of inflammatory mediators into the periphery with developing systemic inflammatory responses. Systemic inflammation is currently considered one of the therapeutic targets for AD treatment, that necessitates in-depth study of this phenomenon in appropriate non-transgenic animal models. This study was aimed to explore systemic inflammatory manifestations in rats with Aβ1-40-induced AD. The impairment of spatial memory and cognitive flexibility in Aβ1-40-lesioned rats was accompanied by pronounced systemic inflammation, which was confirmed by commonly accepted biomarkers: increased hematological indices of systemic inflammation (NLR, dNLR, LMR, PLR and SII), signs of anemia of inflammation or chronic diseases, and pro-inflammatory polarized activation of circulating phagocytes. In addition, markers of systemic inflammation strongly correlated with disorders of remote cognitive flexibility in Aβ1-40-lesioned rats. These results indicate, that Aβ1-40-induced AD model permits the investigation of specific element of the disease – systemic inflammation in addition to well reproduced neuroinflammation and impairment of spatial memory and cognitive flexibility. It increases translational value of this well-known model.

Ethanolic Extract of <i>Alternanthera Sessilis</i>: A Potential Therapeutic Agent for Behavioral Improvements in Reserpine-Induced Parkinsonian Rats

The present study evaluated the potential of an ethanol extract from Alternanthera sessilis to alleviate reserpine-induced Parkinson's disease (PD) like behavioural manifestations in rats. The animals were grouped into five: a control group, a group receiving only reserpine, a group treated with levodopa and carbidopa, and two groups given different doses of the Alternanthera sessilis extract. Reserpine was used to mimic PD symptoms, while the extract was administered orally at two different concentrations. The behavioral tests were conducted to assess locomotor activity, grip strength, catalepsy, and rearing activity. Locomotor activity was measured using an actophotometer, where interruptions in light beams caused by the rates were recorded over a 10-minute period. Grip strength was evaluated using a rotarod apparatus, measuring the time taken for rats to fall off individual rods. Catalepsy was assessed through a bar test, measuring the time for rats to descend from a horizontal bar to the base. Rearing activity was observed in a round open field arena, with parameters including the occurrence rate of rearing, general movements score, and duration spent in the center of the arena. The results revealed administration of reserpine led to a decrease in body weight, locomotor activity, muscle coordination, catalepsy score, rearing activity, and grip strength compared to the control group. Conversely, treatment with levodopa and carbidopa resulted in increased values for these parameters. Importantly, administration of Alternanthera sessilis extract showed a dose-dependent reversal of the effects induced by reserpine, with significant increases observed in body weight, locomotor activity, muscle coordination, rearing activity, general movement, and grip strength, indicating its potential therapeutic effects. In conclusion, the present study results suggest that the extract from the Alternanthera sessilis plant might protect brain cells and improve symptoms of Parkinson's disease. However, more research is needed to understand how it works and if it can be used safely and effectively clinical trails.

PO092 / #966 LATERAL CEREBELLAR NUCLEUS CONTRIBUTION TO THE PENTYLENETETRAZOL KINDLING RESISTANCE: E-POSTER VIEWING

Rats, which did not demonstrate fully developed seizures in pentylenetetrazol (PTZ)-kindling development, are resistant. The aim of the work was confined to the investigations of effects of lateral cerebellar nucleus (LCN) electrical stimulation (ES) upon behavioral and EEG manifestations in rats successfully kindled with PTZ (prone ones) and in rats that remained not kindled (resistant ones).

MTEP, a Selective mGluR5 Antagonist, Had a Neuroprotective Effect but Did Not Prevent the Development of Spontaneous Recurrent Seizures and Behavioral Comorbidities in the Rat Lithium–Pilocarpine Model of Epilepsy

Metabotropic glutamate receptors (mGluRs) are expressed predominantly on neurons and glial cells and are involved in the modulation of a wide range of signal transduction cascades. Therefore, different subtypes of mGluRs are considered a promising target for the treatment of various brain diseases. Previous studies have demonstrated the seizure-induced upregulation of mGluR5; however, its functional significance is still unclear. In the present study, we aimed to clarify the effect of treatment with the selective mGluR5 antagonist 3-[(2-methyl-1,3-thiazol-4-yl)ethynyl]-pyridine (MTEP) on epileptogenesis and behavioral impairments in rats using the lithium–pilocarpine model. We found that the administration of MTEP during the latent phase of the model did not improve survival, prevent the development of epilepsy, or attenuate its manifestations in rats. However, MTEP treatment completely prevented neuronal loss and partially attenuated astrogliosis in the hippocampus. An increase in excitatory amino acid transporter 2 expression, which has been detected in treated rats, may prevent excitotoxicity and be a potential mechanism of neuroprotection. We also found that MTEP administration did not prevent the behavioral comorbidities such as depressive-like behavior, motor hyperactivity, reduction of exploratory behavior, and cognitive impairments typical in the lithium–pilocarpine model. Thus, despite the distinct neuroprotective effect, the MTEP treatment was ineffective in preventing epilepsy.

Hemodynamic Changes Provoked through Intravascular Injection of the Echis carinatus Venom in Rats.

Echis carinatus (E. carinatus) is known for its hematological and nephrotoxic properties in the envenomed patients. Based on the limited data upon the cardiovascular changes associated with this dangerous venomous snake in Iran, the current study purposed to evaluate the venom-induced hemodynamic manifestations in rats. Venom (120 µg/kg) was administered intravenously within one minute through the left femoral vein, and the hemodynamic parameters were continuously recorded using a pressure transducer (MLT844, ADInstruments, Australia). The venom caused prominent hypotension leading to death a few minutes after a transient uprise in blood pressure. It also induced a decrease in heart and pulmonary rates, yet it had no arrhythmogenic properties. Additionally, pre-treatment with the pepsin-derived Iranian polyvalent antivenom (30 µl/Kg) completely neutralized the hemodynamic responses but had no effect when instilled two minutes after venom injection. Heparin (300 IU/kg) and epinephrine (1.5 µg/kg) prevented dramatic hypotension when used 10 minutes before venom instillation; however, atropine (1 mg/kg), dexamethasone (1 mg/kg), and ketorolac (10 mg/ml) had no effects. All treated rats were killed post-injection. Histologically, the lung was the most vulnerable organ with mononuclear infiltration, microcystic formation, and significant capillary congestion. Prominent renal pathological deterioration also occurred, including mesangial cell infiltration and diffuse bleeding, leading to acute tubular necrosis. Modest portal inflammation and vascular congestion were observed in the hepatic tissue of the envenomed rats. The crude venom of Iranian Echis carinatus caused hypotension leading to bradycardia, a decrease in pulmonary rate, and death without significant histological changes to the heart.

Early Life Stress Increases Brain Glutamate and Induces Neurobehavioral Manifestations in Rats.

Early life stress (ELS) is associated with an increased risk of developing depression and anxiety disorders. Disturbances of the neurobiological glutamatergic system are implicated in depression; however, the long-term effects of ELS on glutamate (Glu) metabolites remain unclear. Our study used 7T proton magnetic resonance spectroscopy (7T 1H MRS) to detect metabolic Glu in a rat model to investigate maternal deprivation (MD)-induced ELS. MD was established in Sprague-Dawley rats by periodic separation from mothers and peers. Changes in the hippocampal volume and Glu metabolism were detected by 7T 1H MRS after testing for depression-like behavior via open field, sucrose preference, and Morris water maze tests. Adult MD offspring exhibited depression-like behavior. Compared to the control, the MD group exhibited reduced ratio of central activity time to total time and decreased sucrose consumption (p < 0.05). MD rats spent less time in the fourth quadrant, where the platform was originally placed, in the Morris water maze test. According to 7T 1H MRS, hippocampus of MD rats had elevated Glu and glutamate + glutamine (Glu+Gln) levels compared with the control group hippocampi, but Gln, γ-aminobutyric acid (GABA), and glutamate + glutamine (Glu+Gln) in the prefrontal cortex of MD rats showed a downward trend. Depression-like behavior and cognition deficits related to ELS may induce region-specific changes in Glu metabolism in the prefrontal cortex and hippocampus. The novel, noninvasive 7T 1H MRS-identified associations between Glu levels and ELS may guide future clinical studies.

Early Life Stress Increases Brain Glutamate and Induces Neurobehavioral Manifestations in Rats

Background: Early life stress (ELS) is associated with an increased risk of developing depression and anxiety disorders. Disturbances of the neurobiological glutamatergic system are implicated in depression; however, the long-term effects of early life stress on glutamate (Glu) metabolites remain unclear. Our study used 7T proton magnetic resonance spectroscopy (7T 1 HMRS) to detect metabolic Glu in a rat model to investigate maternal deprivation (MD)-induced ELS. Methods: MD was established in Sprague-Dawley rats by periodic separation from mothers and peers. Changes in the hippocampal volume and Glu metabolism were detected by 7T 1 HMRS after testing for depression-like behavior via open field, sucrose preference, and Morris water maze tests. Findings: Adult MD offspring exhibited depression-like behavior. Compared to control, the MD group exhibited reduced ratio of central activity time to total time and decreased sucrose consumption (18 ± 6 g vs. 31 ± 12 g, p = 0·02). MD rats spent less time in the fourth quadrant, where the platform was originally placed, in the Morris water maze test. According to 7T 1 HMRS, MD rats had elevated Glu and glutamate+glutamine (Glu+Gln) levels compared with the control group hippocampi, but Gln and gamma-aminobutyric acid (GABA), glutamate+glutamine (Glu+Gln) in the prefrontal cortex of MD rats showed a downward trend. Interpretation: Depression-like behavior and cognition deficits related to ELS may induce region-specific changes in Glu metabolism in the prefrontal cortex and hippocampus. The novel, noninvasive 7T 1 HMRS-identified associations between Glu levels and ELS may guide future clinical studies. Funding Statement: The Key Program of the National Natural Science Foundation of China, No. 30930027; Program of the National Natural Science Foundation of China, No. 60971075; Natural Science Foundation of Guangdong Province of China, Nos.S2011010005194 and 2015A030313444; Shantou University Scientific Research Foundation for the Doctoral Scholar of China, No.NTF10010; The Department of Education, Guangdong Government under the Top-tier University Development Scheme for Research and Control of Infectious Diseases of China, No. 2015034. Declaration of Interests: The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest. Ethics Approval Statement: All procedures used in the study were reviewed and approved by the Ethics Committee of School of Medicine, Shantou University Medical College, and comply with the National Institutes of Health’s Guide for the Care and Use of Laboratory Animals (NIH publication no. 85-23, revised 1985). In the handling and care of all animals, we followed the international guiding principles for animal research, as stipulated by the World Health Organization (WHO) Chronicle (World Health Organization, 1985), as adopted by the Laboratory Animal Center, Shantou University Medical College.

Comparison of the hypoglycemic and antithrombotic (anticoagulant) actions of whole bovine and camel milk in streptozotocin-induced diabetes mellitus in rats

People with diabetes are at higher risk of fatal thromboembolic accidents in the cerebral and coronary circulations, especially stroke and ischemic heart disease. We have previously described the hypoglycemic, hypolipidemic, and anticoagulant activity of orally administered camel milk in streptozotocin-induced diabetic rats. In the present study in the same animal model, we extended these observations by comparing camel milk and the more available and widely consumed bovine milk with respect to their antidiabetic and antithrombotic actions. Rats were rendered diabetic by intraperitoneal streptozotocin (65 mg/kg), and then camel milk or bovine milk was administered orally for 8 wk. We evaluated the changes in body weight, fasting blood glucose, glucose tolerance, blood coagulation profile, and platelet function. Diabetic rats developed weight loss, hyperglycemia, glucose intolerance, inhibition of platelet aggregation responses to arachidonic acid and adenosine diphosphate, a marked decrease (>50%) in plasma fibrinogen levels, and short activated partial thromboplastin time. Treatment with camel milk or bovine milk reversed these abnormalities, resulting in weight gain, decreased blood glucose levels, and improved glucose tolerance. Despite the more remarkable antidiabetic action of camel milk, treatment with bovine milk was more effective in correcting plasma fibrinogen levels and restoring inhibited platelet aggregation responses. Long-term administration of camel milk or bovine milk counteracted streptozotocin-induced metabolic manifestations in rats, maintained platelet function, and abolished coagulopathy-associated fibrinogen consumption. Notably, the antidiabetic effect of camel milk was more pronounced than that of bovine milk, but bovine milk exhibited more potent anticoagulant activity than camel milk. These findings should encourage further clinical trials to assess the efficiency of camel milk and bovine milk or their derived peptides as food supplements or potential nonpharmacological therapies for dysglycemia and the vascular complications of diabetes mellitus.

Sex differences in the central and peripheral manifestations of ischemia-induced heart failure in rats.

Sex differences in the presentation, outcome, and responses to treatment of systolic heart failure (HF) have been reported. In the present study, we examined the effect of sex on central neural mechanisms contributing to neurohumoral excitation and its peripheral manifestations in rats with HF. Male and female Sprague-Dawley rats underwent coronary artery ligation (CL) to induce HF. Age-matched rats served as controls. Ischemic zone and left ventricular function were similar 24 h and 4 wk after CL. Female rats with HF had a lower mortality rate and less hemodynamic compromise, pulmonary congestion, and right ventricular remodeling 4 wk after CL. Plasma angiotensin II (ANG II), arginine vasopressin (AVP), and norepinephrine levels were increased in HF rats in both sexes, but AVP and norepinephrine levels increased less in female rats. In the hypothalamic paraventricular nucleus, a key cardiovascular-related nucleus contributing to neurohumoral excitation in HF, mRNA levels for the proinflammatory cytokines tumor necrosis factor-α and interleukin-1β as well as cyclooxygenase-2 and the ANG II type 1a receptor were increased in HF rats of both sexes, but less so in female rats. Angiotensin-converting enzyme 2 protein levels increased in female HF rats but decreased in male HF rats. mRNA levels of AVP were lower in female rats in both control and HF groups compared with the respective male groups. Activation of extracellular signal-regulated protein kinases 1 and 2 increased similarly in both sexes in HF. The results suggest that female HF rats have less central neural excitation and less associated hemodynamic compromise than male HF rats with the same degree of initial ischemic cardiac injury. NEW & NOTEWORTHY Sex differences in the presentation and responses to treatment of heart failure (HF) are widely recognized, but the underlying mechanisms are poorly understood. The present study describes sex differences in the central nervous system mechanisms that drive neurohumoral excitation in ischemia-induced HF. Female rats had a less intense central neurochemical response to HF and experienced less hemodynamic compromise. Sex hormones may contribute to these differences in the central and peripheral adaptations to HF.

Design and Characterization of Apocynin Loaded PLGA Nanoparticles and their In vivo Efficacy in Hyperoxaluric Rats.

Apocynin has become a drug of choice in NADPH oxidase induced pathological conditions. Hyperoxaluria is one such pathological condition where NADPH oxidase is involved in eliciting renal injury. Recently apocynin has shown to reverse the transcriptome profile of the NADPH oxidaseassociated genes and reduced oxidative burden in hyperoxaluric animals. The poor solubility of this drug creates certain apprehensions about its bioavailability. PLGA (Poly Lactic co-Glycolic Acid) encapsulation of drug nanoparticles have showed to induce sustain release and henceforth enhance the efficiency and bioavailability of drugs. Therefore, the present study is aimed to envisage a novel approach of synthesizing apocynin doped PLGA nanoparticles. The PLGA nanoparticles (both unloaded and loaded) were prepared using solvent extraction method and analyzed for size and stability by Dynamic Light Scattering (DLS), TEM (transmission electron microscopy) and zeta potential. Furthermore, the drug release and encapsulation efficiency of the drug was calculated in vitro. The nanoencapsulation formed was stable with desired size (217-259 nm) and posses a controlled drug release of 20%. Further this nanoencapsulation was explored for its potential to reduce hyperoxaluric manifestations in rats given ethylene glycol with ammonium chloride for 9 days. In comparison to free apocynin, it was found that nanoparticles containing apocynin showed moderately better results in vivo by maintaining serum urea and createnine levels. These nanoparticles can be used in diseases where a sustained release of apocynin is required.

Reduction of manganese intake improves neuropsychological manifestations in rats with minimal hepatic encephalopathy

Brain manganese deposition is led by liver dysfunction and/or portal-systemic shunting in minimal hepatic encephalopathy (MHE). Manganese is toxic and can cause cognitive disorders and extrapyramidal symptoms. Thus, reduction of manganese intake might be considered as a potential treatment strategy for MHE. In this study we aimed to investigate whether low- or no-manganese feed can improve the neuropsychological manifestations in MHE rats. Rats with MHE were established by partially ligating the portal vein and fed a manganese diet (MHE-M, 10mg per kg feed; n=24), a no-manganese diet (MHE-N; n=24) and a half-manganese diet (MHE-H; n=24) for 2, 4, 6 and 8weeks, with six rats in each subgroup. Morris water maze (MWM), open-field test and narrow beam test (NBT) were used to evaluate the cognitive and locomotor situations. Fasted blood ammonia, manganese content and glutamine synthetase (GS) activity in basal ganglia and cortex were measured. A significantly longer MWM escape latency, less locomotor activity, longer NBT latency and total time, higher blood ammonia, higher brain manganese content and GS activity were found in MHE-M rats. However, a significantly shorter MWM escape latency, increased locomotor activity, shorter NBT latency and total time, lower blood ammonia, lower brain manganese content and lower GS activity were found in MHE-N rats after no-manganese feed treatment. Partial improvements were found in MHE rats with half-manganese feed treatment. Reduction of manganese intake can significantly improve the cognitive and locomotor situations in MHE rats by reducing brain manganese content and regulating GS activity.

Prenatal Stress+Morphine and Postnatal Re-exposure to Stress Alter Pentylenetetrazol-Induced Epileptic Manifestations in Rats

We studied effects of restraint-induced stress and morphine co-administration within the prenatal period and of re-exposure to stress at the end of infancy on the body mass and pentylenetetrazol-induced epileptic manifestations in rats. Pregnant rats were divided into six groups (control, restraint stressed, saline, morphine, stress+saline, and stress+morphine). In the stressed groups, pregnant rats were subjected to restraint stressing twice per day for three consecutive days (starting on pregnancy day 15). Rats in saline and morphine groups received saline and morphine subcutaneously on the same days. In the morphine/saline+stressed groups, rats were exposed to stress and received morphine/saline simultaneously. Control rats were used intact. The pups were weighed at postnatal days (PD) 1, 15, and 22. On P22, half of the pups were re-exposed to stress; then, pentylenetetrazol (PTZ)-induced seizures were recorded. The offspring body mass was significantly smaller in stressed, morphine, and stressed+morphine groups compared to the control. The time to onset of the first tonic-clonic seizure was shorter, while the duration and number of tonic-clonic attacks were significantly greater in the stressed+morphine group compared to other groups. Re-exposure to stress decreased the number of clonic seizures. The number of leg-opening and tail rigidity episodes was smaller in female offspring compared to male ones. Co-administration of restraint stress and morphine within the prenatal period reduces the offspring body mass and increases the seizure vulnerability more severely compared to the respective individual effects In addition, prenatal stress exerts stronger effects on the neural development and epileptic behaviors of the offspring than postnatal stress.

Co-administration of metformin and N-acetylcysteine with dietary control improves the biochemical and histological manifestations in rats with non-alcoholic fatty liver.

Non-alcoholic fatty liver disease (NAFLD) is a burgeoning health problem that affects 1/3 of the adult population and an increasing number of children in developed countries. Oxidative stress and insulin resistance are the mechanisms that seem to be mostly involved in its pathogenesis. This study was conceived in a NAFLD rat model to evaluate the efficacy of both metformin (MTF) and N-acetylcysteine (NAC) with dietary control on biochemical and histologic liver manifestations. Rats were classified into nine groups; normal (I), NAFLD-induced by feeding high-fat diet (HFD; II) for 12 weeks, NAFLD switched to regular diet (RD; III), NAFLD-HFD or -RD treated with MTF in a dose of 150 mg/kg (IV, V), NAC in a dose of 500 mg/kg (VI, VII) or MTF+NAC (VIII, IX) respectively for 8 weeks. After 20 weeks, the rats in group II showed notable steatosis, lobular inflammation, fibrosis accompanied with elevated (P < 0.05) serum alanine transaminase (ALT), aspartate aminotransferase (AST), alkaline phosphatase (ALP), gamma glutamyl transferase (γ-GT), cholesterol, triglycerides, LDL, VLDL, leptin, tumor necrosis factor (TNF-α), transforming growth factor (TGF-β1) and hepatic malondialdehyde (MDA) compared with group I. Meanwhile, hepatic superoxide dismutase (SOD), glutathione GSH with serum HDL, adiponectin were significantly decreased (P < 0.05). These changes were to a less extent in group III. MTF or NAC individually resulted in improvement of most of these biochemical and histological parameters. These improvements were more pronounced in the combined groups VIII and IX versus each drug alone. NAC supplementation concomitant with MTF could be beneficial for the treatment of NAFLD and prevention of nonalcoholic steatohepatitis (NASH).

Decitabine Improves the Clinical Manifestations of Rats With l-NAME-Induced Pre-eclampsia: A Potential Approach to Studying Pre-eclampsia

Objective: Pre-eclampsia is a major cause of maternal mortality and morbidity. Conditions with low oxygen tension are regarded as a key factor. Decitabine can partly attenuate the effects of hypoxia. This research was designed to investigate the effects of decitabine in rats with NG-Nitro-L-arginine Methyl Eater (L-NAME) induced pre-eclampsia and to explore the molecular mechanisms. Methods: A Wistar rat model of pre-eclampsia was established by intraperitoneal injection of L-NAME, and the intervention reagent was decitabine. Blood pressure (BP) and 24-h urinary protein were monitored. The expression of Mammary Serine Protease Inhibitor (SERPINB5, maspin) in the placenta was detected by reverse transcriptase-polymerase chain reaction (RT-PCR) and western blotting. Results: Systolic BP in the tail artery of pregnant rats was increased by more than 30 mm Hg, and 24-h urinary protein was significantly increased after L-NAME was added. After decitabine treatment, blood pressure and 24-h urinary protein were significantly decreased. The expression of SERPINB5 in the placenta significantly increased after L-NAME was added. Decitabine significantly elevated the expression of SERPINB5 in the placenta of rats with L-NAME-induced preeclampsia. Conclusion: Decitabine reduced 24-h urinary protein and partly decreased blood pressure of pre-eclampsia in late pregnancy in rats with L-NAME-induced pre-eclampsia and increased the expression of SERPINB5, but the molecular mechanism of decitabine's effect remains unknown. This research provided a potential approach to studying the pathogenesis, treatment and prevention of pre-eclampsia.

The role of the dorsolateral funiculi in the pain relieving effect of spinal cord stimulation: a study in a rat model of neuropathic pain.

Activation of the dorsal columns is relayed to supraspinal centers, involved in pain modulation, probably via the descending fibers in the dorsolateral funiculi (DLF). The present study examines the role of the DLF in the attenuation of pain-related signs by spinal cord stimulation (SCS). Several groups of rats were subjected to nerve injury and to chronic bilateral DLF lesions at C5-7 level. In each animal, two sets of miniature electrodes were implanted, a caudal system placed in the dorsal epidural space at low thoracic level and another implanted over the dorsal column nuclei, rostral to the lesions. Stimulation (50 Hz, 0.2 ms; 70 % of motor threshold) was applied for 5 min via either of the electrodes. Behavioral tests were used to assess the effects of SCS on the nerve injury-induced mechanical and cold hypersensitivity and heat hyperalgesia. Prior to application of SCS, antagonists to either of GABAA or B, 5-HT1 or 1-2 or α/β-adrenergic receptors were injected i.p. Both stimulations produced comparable decreases (80-90 % of the control) of neuropathic manifestations in rats with intact spinal cords. DLF lesions attenuated the effects of both types of stimulation by about 50 %. Pretreatment with receptor antagonists differentially counteracted the effects of rostral and caudal stimulation; the inhibition with rostral stimulation generally being more prominently influenced. These results provide further support to the notion of important involvement of brainstem pain modulating centers in the effects of SCS. A major component of the inhibitory spinal-supraspinal-spinal loop is mediated by fibers running in the DLF.

Exogenous IL-10 affects the expression of certain cytokines by Th cells and Th17 cells in rats with al-lergic rhinitis

Objective To investigate the expression of IFN-γ, IL-5, IL-17 and TGF-βby Th cells and Th17 cells in rats with allergic rhinitis upon the intervention of IL-10.Methods SD rats were ran-domly divided into three groups including allergic rhinitis （ AR ） group, IL-10 treated group and control group （n=10）.Rats in AR group and IL-10 treated group were sensitized by injection of ovalbumin （OVA） and aluminum hydroxide on the 1st, the 7th and the 14th days.The rats treated with equal volume of saline were set up as the control.The corresponding interventions （ OVA, OVA and IL-10, saline） were respec-tively given to rats in each group on the 21th day for 7 consecutive days.The clinical manifestations in rats were observed within 30 minutes after each administration.Serum samples were collected at 48 hours after the last challenge for the detection of IgE and OVA-sIgE.ELISA and Western blot assay were performed to detect IFN-γ, IL-5, IL-17 and TGF-βin nasal mucosa samples.Results Some characteristic symptoms of AR were observed in rats from AR group and IL-10 treated group.Compared with IL-10 treated rats, rats in AR group showed severe clinical symptoms such as constant rubbing and tearing of the eyes （P〈0.05）.The levels of IgE and OVA-sIgE in serum samples and the levels of IFN-γ, IL-5, IL-17 and TGF-βin nasal tis-sues were significantly increased in rats with RA （P〈0.05）, but were reduced with IL-10 intervention （P〈0.05）.Conclusion Exogenous IL-10 could be used to treat AR by reducing the expression of IFN-γ, IL-5, IL-17 and TGF-βin nasal tissues. Key words: Allergic rhinitis Th1 cells Th2 cells Th17 cells Cytokine

Immunotoxic manifestations in rats following inhalative exposure to furfural vapors

Furfural is an industrial compound used as a process intermediate and as a solvent; it poses a potential inhalation hazard in occupational settings. This study was carried out to find furfural-induced immunotoxicity in Wistar rat following inhalative exposure. The weights of thymus and lymph node were found decreased, while the weights of the liver and the adrenal gland were significantly increased following furfural exposure. Delayed-type hypersensitivity response was found decreased in furfural vapors-exposed animals when compared to that of control animals. The phagocytic index of peritoneal and alveolar exudates showed significant decrease and was most prominent (90%) in 30 days-exposed groups. The number of anti-rat anti-sheep red blood cell immunoglobulin M plaque forming cells of spleen got decreased in furfural-exposed groups in comparison to control. Taken together, this study indicates that inhalation of furfural induces immunotoxic manifestations that could lead to severe immunological disorders.

Brainstem injection of lidocaine releases the descending pain-inhibitory mechanisms in a rat model of mononeuropathy

Lidocaine injections in the rostral ventromedial medulla (RVM) have been shown to produce significant reduction of neuropathic manifestations in rats. This effect has been attributed to selective block of a pain descending facilitatory system, responsible for chronic pain. However, recent observations from our laboratory did not provide confirmation to this hypothesis. We aimed, therefore, to investigate the spinal synaptic mechanisms activated by lidocaine injections in the RVM.Rats were subjected, under deep anesthesia, to the induction of mononeuropathy on one hindpaw, and to the stereotaxic implantation of chronic cannulae in the RVM for the injection of lidocaine or GABA antagonists. Implanted intrathecal catheter in the lumbosacral space was used for the injection of specific antagonists to GABA, 5HT, glycine, noreadrenaline and dopamine, prior to lidocaine. Tactile and cold hyperreactivity and heat hyperalgesia were assessed using von Frey hair filaments, acetone drop test and heat-induced paw withdrawal, respectively.Lidocaine injections produced significant inhibition of all neuropathic manifestations. Intrathecal injection of antagonists to GABA (bicucullin, picrotoxin and saclofen), serotonin 5HT1–2 (ketanserin and methysergide) and α- (phentoalmine, yohimbine) and β- (propranolol) adrenergic receptors, suppressed the lidocaine inhibitory effects; while partial or no attenuation were observed following pretreatment with glycine and dopamine D2/3 antagonists. Comparable effects were observed with RVM injection of GABA antagonists.Lidocaine injection in the RVM results in a release of the descending pain-inhibitory systems from a tonic gabaergic inhibition. This descending system involves the activation of gabaergic, serotonergic and adrenergic mechanisms at the level of the spinal dorsal horn.

Effects of Memantine on Convulsive Reactions and the Organization of Sleep in Krushinskii–Molodkina Rats with an Inherited Predisposition to Audiogenic Convulsions

Krushinskii-Molodkina rats, which have a genetic predisposition to audiogenic convulsions, are used as a natural animal model for studies of the actions of anticonvulsants. It is important to understand the extent to which changes in glutamatergic synaptic transmission is involved in the mechanisms producing convulsive states and in the functional organization of the sleep-waking cycle in rats of this strain. The present report describes experiments addressing this, in which i.m. doses of 5 and 10 mg/kg of a noncompetitive NMDA glutamate receptor antagonist of the memantine type were given at different times (30 min, 1, 2, and 3 h) before presentation of sound stimuli (sine-wave tones at 8 kHz, 90 dB). Effects on the latent periods of the initial motor excitation, the appearance of clonic convulsions of different intensities, and, finally, tonic convulsions with limb and tail extension were evaluated. The greatest attenuation of convulsive seizures, to a level consisting only of motor excitation, was obtained in 60% of the rats between 1 and 2 h after administration. There were no differences between the effects of doses of 5 and 10 mg/kg. When doses were given 3 h before sound provocation, convulsive reactions became more marked than at 2 h, though they were nevertheless more marked than in controls. Krushinskii-Molodkina rats with chronically implanted electrodes for recording brain electrical activity were used to study the effects of memantine on the organization of sleep. These experiments showed that the rats' sleep during the first hour after dosage consisted only of short episodes of superficial slow-wave sleep, and that even this sleep disappeared completely 54.4 +/- 4.9 and 39.9 +/- 5.2 min after administration of the agent at doses of 5 and 7 mg/kg, respectively. Rats showed a complete absence of sleep for 2 and 2.5 h, respectively, after which episodes of slow-wave sleep reappeared. The first episodes of REM sleep was seen in rats only after 3.3 +/- 0.2 and 3.7 +/- 0.2 h after memantine injections. The appearance of these episodes provided evidence that the effects of memantine on the activity of the somnogenic system of the animals' brains were complete and that recovery of the normal organization of the sleep-waking cycle had started. The synchronicity and codirectionality of the blocking action of memantine on sleep organization and measures of audiogenic convulsions in Krushinskii-Molodkina rats is evidence for the involvement of glutamatergic synapses with NMDA receptors in both the regulation of the somnogenic systems and the pathogenesis of epileptiform manifestations in rats.

The inhibitory effect of Hypericum perforatum extract on morphine withdrawal syndrome in rat and comparison with clonidine

The effects of Hypericum perforatum (St John's wort) on morphine withdrawal syndrome and comparison with clonidine have been investigated in morphine-dependent rats. Adult male Wistar rats were subjects. The frequencies of withdrawal behavioral signs (rearing, teeth chattering and jumping) induced by naloxone challenge were demonstrated in morphine dependent rats receiving Hypericum perforatum extract (HPE), saline or clonidine. The withdrawal behavioral manifestations in rats were inhibited significantly by chronic co-administration of Hypericum perforatum extract or clonidine with morphine. This study showed that clonidine was more effective than HPE at a dose of 0.4 mL/200 g and there was no significant statistical difference between the mean frequency of withdrawal signs of HPE at a dose of 0.8 mL/200 g compared with clonidine (0.2 mg/kg i.p.) but at a dose of 1.2 mL/200 g of HPE was significantly stronger than clonidine in attenuation of the morphine withdrawal syndrome.The findings suggest that HPE is capable of reducing the symptoms of opiate withdrawal and its effectiveness may be equivalent to clonidine in reducing the opiate withdrawal syndrome and may have human therapeutic potential.