Injection Of Sodium Nitroprusside Research Articles

Calcitonin gene-related peptide receptor antagonism reduces motion sickness indicators in mouse migraine models.

Migraine and vestibular migraine are disorders associated with a heightened motion sensitivity that provoke symptoms of motion-induced nausea and motion sickness. VM affects ∼3% of adults in the USA and affects three-fold more women than men. Triptans (selective serotonin receptor agonists) relieve migraine pain but lack efficacy for vertigo. Murine models of photophobia and allodynia have used injections of calcitonin gene-related peptide (CGRP) or other migraine triggers, such as sodium nitroprusside (SNP), to induce migraine sensitivities in mice to touch and light. Yet, there is limited research on whether these triggers affect motion-induced nausea in mice, and whether migraine blockers can reduce these migraine symptoms. We hypothesized that systemic delivery of CGRP or SNP will increase motion sickness susceptibility and motion-induced nausea in mouse models, and that migraine blockers can block these changes induced by systemically delivered CGRP or SNP. We investigated two measures of motion sickness assessment [motion sickness index (MSI) scoring and motion-induced thermoregulation] after intraperitoneal injections of either CGRP or SNP in C57BL/6J mice. The drugs olcegepant, sumatriptan and rizatriptan were used to assess the efficacy of migraine blockers. MSI measures were confounded by CGRP's effect on gastric distress. However, analysis of tail vasodilatations as a surrogate for motion-induced nausea was robust for both migraine triggers. Only olcegepant treatment rescued tail vasodilatations. These preclinical findings support the use of small molecule CGRP receptor antagonists for the treatment of motion-induced nausea of migraine, and show that triptan therapeutics are ineffective against motion-induced nausea of migraine.Trial Registration: Not Applicable.

Convenient Application of a Compact-Type Magnetic Resonance Imager with Blood Pool Contrast Agent Gadolinium-Conjugated Dextran to Assess Vascular Abnormalities in Experimental Animals.

Vascular lesions are symptomatic of lifestyle-related diseases and include blood clots, coarctations, aneurysms, and apoplexy. Furthermore, increased blood vessel permeability is usually observed in tumors. To develop therapeutic drugs treating vascular lesions and tumors, methods with which the vascular abnormalities can be readily assessed in experimental animals are necessary. In this paper, a laboratory-size magnetic resonance imaging (MRI) system with permanent magnets, a compact-type MRI, was used to assess vascular abnormalities. Blood vessels in the head of a mouse were clearly visualized with the compact-type MRI in combination with gadolinium-diethylenetriamine-N,N,N',N″,N″-pentaacetic acid chelate (Gd-DTPA)-linked dextran (Gd-Dex) as blood pool contrast agents. The rat middle cerebral artery was imaged, and artery occlusion was identified. The difference between normal and occluded rats became more apparent upon intravenous injection of sodium nitroprusside, a nitric oxide (NO) donor. The system also visualized poor circulation in a rat saphenous artery by femoral artery occlusion. In a tumor-bearing mouse, a compact-type MRI visualized accumulation of Gd-Dex similar to that of small molecular Gd-DTPA, in the rim of tumor. Gd-Dex accumulation was more consistent than that of Gd-DTPA. Tumor vasculature was characterized by estimating the plasma-to-tumor interstitial tissue transfer constant, Ktrans, of Gd-Dex and fractional plasma volume, Vp, using image data. These results demonstrate the efficacy of a compact-type MRI in combination with Gd-Dex for vascular abnormality assessment in both mice and rats.

Effect of Exogenous Nitric Oxide on Enterocytozoon hepatopenaei Copy Numbers and Immunity of Exopalaemon carinicauda

To explore the effect of nitric oxide (NO) on Enterocytozoon hepatopenaei (EHP) invading the shrimp, sodium nitroprusside was used as an exogenous NO donor to investigate the effects of different concentrations (0 μg/L (control group), 0.3 μg/L, 0.6 μg/L, and 0.9 μg/L) of sodium nitroprusside on the EHP copy number and the structure in the hepatopancreas of Exopalaemon carinicauda infected by EHP. The results showed that the EHP copy number in the sodium nitroprusside group was significantly lower than that in the control group, and the hepatopancreas in the sodium nitroprusside injection group had less structure damage than the control group. Additionally, superoxide dismutase (SOD) activity in the control group and 0.3 μg/L groups increased and then decreased, while alkaline phosphatase (AKP) activity decreased and then increased, with the same trend, and, the inducible nitric oxide synthase (iNOS) activity in the haemolymph of the 0.3 μg/L group was significantly higher than that of the control group at 3 days ( P < 0.05 ). The NO content the 0.3 μg/L group was also higher from 1 to 4 days than that in the control group and significantly higher than that in the control group at 3 days ( P < 0.05 ). The injection of NO could reduce the EHP copy number in infected E. carinicauda and slow down the pathological changes in the hepatopancreas structure, which might be related to the increase in NO content.

Effect of sodium nitroprusside on feeding behavior, voluntary activity, and cloacal temperature in chicks

Nitric oxide (NO) is a well-known gaseous signaling molecule that is involved in a variety of physiological and pathological processes in vertebrates. The role of NO in physiological responses of birds has been investigated primarily using NOS inhibitors. Therefore, the effect of the absence of NO is well characterized. However, there is little knowledge on the effects of abundant NO in birds, which is the case in birds that have infections. Therefore, the purpose of the present study was to determine if intraperitoneal (IP) and intracerebroventricular (ICV) injections of sodium nitroprusside (SNP), a NO donor, affected feed intake, voluntary activity, cloacal temperature, crop emptying rate, and blood constituents in domesticated chicks (Gallus gallus) as model birds. We found that both IP and ICV injections of SNP significantly decreased feed intake while there was little effect on voluntary activity. Cloacal temperature was temporarily, but significantly, decreased by both types of injection of SNP. Additionally, both IP and ICV injections of SNP significantly decreased the crop emptying rate. The IP injection of SNP significantly increased the plasma concentrations of NO2/NO3, which are metabolites of NO, and corticosterone, and decreased the plasma glucose concentrations, while the ICV injection had no effect. The IP injection of SNP also showed the tendency to increase the nitrotyrosine level, to increase superoxide dismutase activity, and to decrease catalase activity in the plasma. These results suggest that under specific situations which produce abundant NO such as infection, NO would induce anorexia, hypothermia, inhibition of feed passage, and activation of the hypothalamus-pituitary-adrenal axis in chicks.

Effectiveness of Intra-Coronary Injection of Sodium Nitroprusside for the Treatment of Coronary No-Reflow through Punctured Coronary Balloon

Rapid restoration of thrombolysis in myocardial infarction III in case of no-reflow during percutaneous coronary intervention is imperative. Application of punctured coronary balloon intracoronary injection of sodium nitroprusside is a prompt, safe and effective method. To investigate the effectiveness of intracoronary injection of sodium nitroprusside via punctured coronary balloon in the treatment of no-reflow in coronary artery is the main objective of the study. We retrospectively analyzed 76 patients treated with intracoronary injection of sodium nitroprusside via punctured coronary balloon for coronary no-reflow. All 76 patients successfully completed intracoronary injection of sodium nitroprusside with the improvement of no-reflow in coronary artery for thrombolysis in myocardial infarction grade III in 74 patients. There were two complications which occurred in the early application of this technique. One was a punctured coronary balloon fracture left in the distal coronary artery and the other was a difficult pullback of the punctured coronary balloon catheter. After improving the application method, later no more complications occurred in 67 patients and no complications such as coronary guide wire pulling out of the coronary artery, coronary artery dissection, coronary artery perforation and coronary artery air embolism occurred. Coronary no-reflow treatment with intracoronary injection of sodium nitroprusside via punctured coronary balloon is safe and effective when properly applied.

Sodium nitroprusside injection immediately before balloon inflation during percutaneous coronary intervention.

BACKGROUNDNo reflow or slow flow frequently occurs during percutaneous coronary inter-vention (PCI) and it is associated with adverse outcomes. Strategies should be undertaken to prevent its occurrence.AIMTo observe whether conventional target intracoronary administration of sodium nitroprusside immediately before balloon inflation can reduce the incidence of no reflow and slow flow, which are defined as thrombolysis in myocardial infarction flow grade ≤ II during PCI. METHODSA retrospective study was conducted in 740 patients with coronary artery disease admitted to Gansu Provincial Hospital of Traditional Chinese Medicine between January 2016 and October 2020. Among them, 360 patients receiving sodium nitroprusside immediately before balloon inflation during PCI were enrolled in an experimental group between January 2019 and October 2020 and 380 patients receiving sodium nitroprusside after incident no reflow and slow flow during PCI were enrolled in a control group between January 2016 and January 2019. The occurrence of no reflow and slow flow was compared between the two groups and left ventricular end-diastolic diameter (LVEDD) and left ventricular ejection fraction (LVEF) were detected 1 mo after the operation. RESULTSAfter treatment, the proportion of patients with thrombolysis in myocardial infarction flow grades 0 to II was lower in the experimental group than in the control group (P < 0.05). At 1 mo after treatment, LVEDD was lower and LVEF was higher in the experimental group than in the control group (P < 0.05). In terms of incidence of adverse cardiovascular events within 1 mo after treatment, in the experimental group, malignant arrhythmia occurred in three patients, intractable myocardial ischemia in three, congestive heart failure in four, and recurrent myocardial infarction in five; one patient died. In the control group, malignant arrhythmia occurred in eight patients, intractable myocardial ischemia in five, congestive heart failure in seven, and recurrent myocardial infarction in 14; two patients died. The incidence of adverse cardiovascular events was 4.4% in experimental group which was lower than that of the control group at 1 mo after operation (9.5%; P < 0.05). CONCLUSIONAdministration of sodium nitroprusside into target vessels immediately before balloon inflation can significantly reduce the incidence of no reflow and slow flow, improve LVEDD and LVEF, and reduce the incidence of adverse cardio-vascular events in patients treated by PCI. It is worthy of clinical promotion.

A simple isocratic LC method for quantification of trace-level inorganic degradation impurities (ferricyanide, ferrocyanide, nitrite, and nitrate) in sodium nitroprusside injection and robustness by quality using design approach.

This study developed and validated a trace-level quantification inorganic impurities method using reversed-phase HPLC and performed the robustness check using quality-by-design approach by varying the multiple factors simultaneously. This method is economical and simple and exhibits its stability-indicating nature [for the determination of ferrocyanide ([Fe(CN)₆]4- ), ferricyanide ([Fe(CN)6 ]3- ), nitrate (NO3 - ), and nitrite (NO2 - )] in sodium nitroprusside (SNP) drug substance and liquid dosage form. Chromatographic separation was achieved using a USP L43 column (ACE PFP, 150×4.6 mm, 3 μm) with a simple isocratic elution. The buffer consists of potassium dihydrogen phosphate (50 mM), tetrabutylammonium hydrogen sulfate (9 mM), and tetrabutylammonium hydroxide (25 mM). The buffer pH was adjusted to 7.2 with tetrabutylammonium hydroxide. The mobile phase was mixed with the buffer and acetonitrile (68:32 v/v). The flow rate was 0.8 mL/min, column temperature was maintained at 30°C, and injection volume was 5.0 μL. The SNP impurities were monitored at 225 nm using a UV detector. Further, the method was validated per the International Council for Harmonisation (ICH) guidelines, and forced degradation studies were carried out under different stress conditions. The detector responses were plotted against concentrations, and correlation was linear (r > 0.999) over the range of 0.8-7.5 μg/mL for ferricyanide; 1.0-37.5 μg/mL for SNP; and 0.2-7.5 μg/mL for ferrocyanide, nitrite, and nitrate. The method repeatability was established for all the impurities with relative standard deviation (%), and the results were found to be less than 2.0.

Maintained barostatic regulation of heart rate in digesting snakes (Boa constrictor).

When snakes digest large meals, heart rate is accelerated by withdrawal of vagal tone and an increased non-adrenergic-non-cholinergic tone that seems to stem from circulating blood-borne factors exerting positive chronotropic effects. To investigate whether this tonic elevation of heart rate impairs the ability for autonomic regulation of heart during digestion, we characterised heart rate responses to pharmacological manipulation of blood pressure in the snake Boa constrictor through serial injections of sodium nitroprusside and phenylephrine. Both fasting and digesting snakes responded with a robust tachycardia to hypotension induced by sodium nitroprusside, with digesting snakes attaining higher maximal heart rates than fasting snakes. Both fasting and digesting snakes exhibited small reductions of the cardiac chronotropic response to hypertension, induced by injection of phenylephrine. All heart rate changes were abolished by autonomic blockade with the combination of atropine and propranolol. The digesting snakes retained the capacity for compensatory heart rate responses to hypotension, despite their higher resting values, and the upward shift of the barostatic response curve enables snakes to maintain the cardiac limb of barostatic regulation for blood pressure regulation.

In Vivo Action of Nitric Oxide Donor Sodium Nitroprusside (SNP) on Mitochondrial Ion Transporter Function in Brain Segments of Immersion-Stressed Air-Breathing Fish ( Anabas testudineus Bloch)

The neuronal circuitries of brain and the corresponding ion transporters contribute to the maintenance of ion homeostasis in fish brain. The sensitivity of these neuronal clusters in response to environmental clues brings neural plasticity and subsequent regulation of stress acclimation. Nitric oxide (NO), a gasotransmitter, is involved in ion transport in many peripheral tissues of fishes including air-breathing fish. However, the role of NO in mitochondrial ion transporter activity has not yet been investigated in fish brain. We, therefore, investigated the short-term in vivo action of a NO donor, Sodium Nitro-Prusside (SNP), on mitochondrial ion transporters such as H + - Ca 2+ - and Mg 2+ -dependent ATPases in brain segments such as Prosen-Cephalon (PC), Mesen-Cephalon (MC) and Meten-Cephalon (MeC) of immersion-stressed Anabas testudineus . Intraperitoneal injection of SNP for 30 min lowered the activities of bafilomycin-sensitive H + ATPase and vanadate sensitive Ca 2+ ATPase in PC, whereas in MeC, these transporters showed significant rise in activities after SNP treatment. The oligomycin-sensitive Mg 2+ ATPase activity showed a significant decrease in PC and MC of brain after SNP treatment in non-stressed fish. Induction of stress by water immersion altered the activities of these ion transporter activities. However, the treatment of SNP in immersed fish showed recovery of the immersion-induced modulation in the activities of these mitochondrial ion transporters. Our data, thus, provide evidence for a decisive role of NO in the recovery process of mitochondrial ion transporters function during immersion stress, confirming a direct differential role of NO in mitochondrial ion homeostasis in teleost brain.

Ketamine: yay or neigh? Implications for cardiovascular regulation and considerations for field use.

Ketamine: yay or neigh? Implications for cardiovascular regulation and considerations for field use.

A VALIDATED RP-HPLC METHOD FOR IMPURITY PROFILING OF SODIUM NITROPRUSSIDE IN INJECTION DOSAGE FORM

Objective: The main objective of this research work is to develop and validate a single reverse-phase high-performance liquid chromatography (RP-HPLC) method. This method should becapable of quantifying all the known, as well as other possible degradation impurities of sodium nitroprusside (SNP) in its injection formulation.&#x0D; Methods: Of allmethod development trails, we have observed better separations between known and degradation impuritiesin Inert sustain C18, (250 x 4.6) mm, 5 µm column at 30 °C temperature. Isocratic elution was carried out by using pH 8.6 phosphate buffer and acetonitrile in the ratio of 65:35 %v/v with a flow rate of 0.8 ml/min. The detection was carried out at 220 nm, with an injection volume of 10 µl.&#x0D; Results: In the proposed method, SNP was eluted at 22.5 min. Nitrite, nitrate, and ferrocyanide were linear from 0.25 to 37 μg/ml, ferricyanide was linear from 1.0 to 37 μg/ml, and SNP was linear from 0.75 to 37 μg/ml. The % RSD for six spiked samples (precision)was found to be less than 0.5 %. Accuracy was performed for known impurities from LOQ to 150 % for a 0.5 % specification level. The resultswere found to be in the acceptance range of 90-110 %. The LOQ concentration of nitrite, nitrate, and ferrocyanide was 0.25 μg/ml each,LOQ offerricyanide and SNP was found to be 1.0 μg/ml and 0.75 μg/ml, respectively. The SNP injection samples were exposed to different degradation conditions, and the results were found specific in the proposed methodology.&#x0D; Conclusion: The proposed RP-HPLC method is specific, precise, accurate, linear, stable, and robust for quantification of known and other possible degradation impurities in SNP injection formulation.

Evaluation of intramuscular sodium nitroprusside injection to improve oxygenation in white-tailed deer (Odocoileus virginianus) anesthetized with medetomidine–alfaxalone–azaperone

ObjectiveIn ungulates, α2-adrenergic agonists can decrease oxygenation possibly through alteration of pulmonary perfusion. Sodium nitroprusside can decrease pulmonary vascular resistance (PVR) and increase cardiac output (Q˙t) through vasodilation. The objective was to determine if sodium nitroprusside would improve pulmonary perfusion and attenuate the increased alveolar–arterial (a–a) gradient resulting from medetomidine–azaperone–alfaxalone (MAA) administration. Study designProspective, randomized, crossover study with a 2 week rest period. AnimalsA group of eight adult female captive white-tailed deer (Odocoileus virginianus). MethodsDeer were administered MAA intramuscularly (IM), and auricular artery and pulmonary artery balloon catheters were placed. Deer spontaneously breathed air. Saline or sodium nitroprusside (0.07 mg kg–1) were administered IM 40 minutes after MAA injection. Heart rate (HR), mean arterial pressure (MAP), mean pulmonary arterial pressure (MPAP), pulmonary artery occlusion pressure (PAOP), right atrial pressure (RAP), Q˙t, arterial pH, PaCO2 and PaO2 were obtained immediately before nitroprusside injection (baseline) and 5, 10 and 15 minutes afterwards. Mixed venous blood samples were obtained at baseline and at 5 minutes. Systemic vascular resistance (SVR), PVR, intrapulmonary shunt fraction (Q˙s/Q˙t), a–a gradient, oxygen delivery (D˙O2) and oxygen extraction ratio (O2ER) were calculated. Statistical analysis was performed with repeated measures analysis of variance with correction factors. A p value < 0.05 was considered significant. ResultsWith nitroprusside, MAP, MPAP, PAOP, RAP, SVR and O2ER significantly decreased and HR, Q˙t and D˙O2 increased compared with baseline and between treatments. There was a significant decrease in PVR and a–a gradient and increase in PaO2 compared with baseline and saline treatment. Changes were not sustained. Conclusions and clinical relevanceNitroprusside temporarily changed hemodynamic variables, increased PaO2 and decreased a–a gradient. Nitroprusside possibly led to better pulmonary perfusion of ventilated alveoli. However, IM nitroprusside at this dose is not recommended because of severe systemic hypotension and short action.

Exacerbated Headache-Related Pain in the Single Prolonged Stress Preclinical Model of Post-traumatic Stress Disorder

Chronic headache pain is one of the most commonly reported comorbid pain conditions with post-traumatic stress disorder (PTSD) patients and resistant to effective treatment, yet no combined preclinical model of the two disorders has been reported. Here, we used a modified chronic headache pain model to investigate the contribution of single prolonged stress (SPS) model of PTSD with sodium nitroprusside (SNP)-induced hyperalgesia. Injection of SNP (2 mg/kg, i.p.) occurred every other day from day 7 to day 15 after initiation of SPS in rats. Paw withdrawal threshold (PWT) to von Frey stimuli and tail flick latencies (TFL) dramatically decreased as early as 7 days after SPS and lasted until at least day 21. Basal PWT and TFL also significantly decreased during the SNP treatment period. The lower nociceptive thresholds recovered in 6 days following the final SNP injection in SNP group, but not in SPS + SNP group. Elevated nociceptin/OFQ (N/OFQ) levels observed in cerebrospinal fluid of SPS rats were even higher in SPS + SNP group. Glial fibrillary acidic protein (GFAP) and N/OFQ peptide (NOP) receptor mRNA expression increased in dorsal root ganglia (DRG) 21 days after SPS exposure; mRNA increases in the SPS/SNP group was more pronounced than SPS or SNP alone. GFAP protein expression was upregulated in trigeminal ganglia by SPS. Our results indicate that traumatic stress exaggerated chronic SNP-induced nociceptive hypersensitivity, and that N/OFQ and activated satellite glia cells may play an important role in the interaction between both conditions.

Attenuated baroreflex in a Parkinson's disease animal model coincides with impaired activation of non-C1 neurons.

Orthostatic hypotension is one of the most common symptoms observed in Parkinson's disease (PD), a neurodegenerative disease caused by death of dopaminergic neurons in the substantia nigra pars compacta (SNc), and it is associated with denervation of the heart and impairment of the baroreflex. Here, we aimed to investigate if the impaired baroreflex was associated with lower activation of cardiovascular brainstem areas in a 6-hydroxydopamine (6-OHDA) animal model of PD. The PD model was generated with male Wistar rats by injection of 6-OHDA or vehicle into the striatum. After 20 or 60days, the femoral vein and artery were cannulated to assess cardiovascular parameters during injection of sodium nitroprusside (SNP) or phenylephrine (Phe). Brainstem slices were submitted to immunohistochemistry and immunofluorescence. After 6-OHDA injection, 75% of the dopaminergic neurons in the SNc were absent, confirming establishment of the PD model. Intravenous (iv) injection of SNP generated reduced hypotension and tachycardia response, and the noncatecholaminergic (nonC1) neurons of the rostral ventrolateral medulla (RVLM) were less activated. Additionally, iv injection of Phe increased blood pressure and bradycardia to the same extent and activated equivalent numbers of neurons in the nucleus of the solitary tract and the caudal ventrolateral medulla as well as cholinergic neurons of the dorsal motor nucleus of the vagus and the nucleus ambiguus between control and PD animals. In summary, these data showed that in the PD model, impairment of cardiovascular autonomic control was observed only during deactivation of the baroreflex, which could be related to reduced activation of non-C1 neurons within the RVLM.

Enhancement of the antipsychotic effect of risperidone by sodium nitroprusside in rats

Recently, a single injection of the nitric oxide donor sodium nitroprusside (SNP) was found to induce a rapid and sustained antipsychotic effect in treatment-resistant schizophrenia (TRS). Moreover, a single i.p. injection of SNP in rats was found to generate both rapid and persisting changes in brain synaptic plasticity, including enhanced excitatory postsynaptic current responses and spine morphology in layer V pyramidal cells in the medial prefrontal cortex (mPFC) brain slices. Here we used the conditioned avoidance response (CAR) test in rats to investigate the antipsychotic-like efficacy of SNP in combination with low-dose risperidone. In addition, we performed microdialysis experiments in freely moving rats to measure neurotransmitter efflux in the mPFC and the nucleus accumbens (NAc). Risperidone caused only 20% suppression of CAR, which is far below the degree of CAR suppression required to predict a significant clinical antipsychotic effect. Addition of a low dose of SNP to risperidone dramatically enhanced the antipsychotic-like effect to a clinically relevant level. SNP significantly enhanced the risperidone-induced dopamine output in the mPFC but not in the NAc. The increased prefrontal dopamine release induced by the drug combination may also improve cognition as indicated by previous preclinical and clinical studies and, furthermore, via enhanced synaptic spine function and morphology in mPFC generate a both rapid and prolonged antipsychotic and pro-cognitive effect. Our results delineate SNP as a promising new treatment option for schizophrenia, including TRS, when added to currently available antipsychotic medication in order to improve efficacy at maintained or even reduced dosage.

Effects of novel hexahydropyrimidine derivatives as potential ligands of M1 muscarinic acetylcholine receptor on cognitive function, hypoxia-induced lethality, and oxidative stress in rodents

The neurodegenerative diseases have a complex pathogenetic mechanism comprising oxidative stress and receptor system dysfunction caused by various damaging factors such as, for example, brain hypoxia. The purpose of this study was to elucidate the influence of hexahydropyrimidine derivatives on learning, memory, and orientation and locomotor activities in the passive avoidance (PA) and open field (OF) tests and to evaluate these compounds for their potential antihypoxic and antioxidant action on normobaric hypercapnic hypoxia and toxic hypoxia models. We demonstrated that compounds 1a and 1e administered as a single 100 mg/kg dose (p.o.) one hour before the tests increased the latency time to enter the dark compartment for the first time and reduced the time spent in the dark compartment on the 2nd, 7th, and 14th days of PAT and increased the number of squares crossed and hole-pokings in the OF test. It was also shown that single administration of compounds 1a and 1e (in 100 mg/kg dose, p.o.) one hour before generation of hypoxia increased the life span of mice under normobaric hypoxia by 30% (P < 0.05) and, after injection of sodium nitroprusside, they decreased the malondialdehyde (MDA) level and increased the catalase level in the brain of mice. According to molecular docking results, compounds 1а and 1е are bound in the orthosteric active site of M1 muscarinic receptor via supramolecular interactions with a number of functional amino acids.The results indicate that hexahydropyrimidine derivatives have a beneficial effect on the memory, learning processes, and orientation and locomotor activities of rats in an unfamiliar environment and exhibit antihypoxic and antioxidant activities under hypoxia in mice. The cognitive enhancement can be mediated by the effect of lead compounds on the M1 muscarinic acetylcholine receptor.

Effects of ginkgo biloba extract on learning and memory and protection of hippocampal neurons in rats with vascular dementia

Objective To investigate the effects of ginkgo biloba extracts (EGb761) on learning and memory and the protective effect on hippocampal neurons in rats with vascular dementia (VD). Methods Ninety rats were randomly divided into sham-operated group, model group and EGb761-treated group, with 30 rats in each group. Rats in each group were examined at 15 days, 1 month and 2 months, with 10 rats in each time point. VD model was established by bilateral carotid artery occlusion combinding with injection of sodium nitroprusside. Morris water maze test was used to detect the learning and memory function of rats. The expression of glial fibrillary acidic protein (GFAP) was observed by immunofluorescence. Western-blot was used to detect the protein expression of P-glycoprotein (P-GP), excitatory amino acid transporters 2(EAAT2), caspase-3 and cleaved caspase-3.RT-PCR was used to detect the mRNA expression of P-GP and EAAT2 in the hippocampus of rats in each group. Results Compared with sham-operated group, the escape latency (EL) was significantly prolonged at each time point in model group (sham-operated group: 15 days(15.52±3.23)s, 1 month(14.21±2.62)s, 2 months(15.37±1.66)s; model group: 15 days(30.35±2.30)s, 1 month(40.78±3.55)s, 2 months(33.88±1.47)s; all P<0.01). The EL of EGb761-treated group was significantly shorter than that of the model group(EGb761-treated group: 15 days(25.69±2.44)s, 1 month(20.78±1.72)s, 2 months(18.23±1.67)s, all P<0.01). Immunofluorescence showed that the expression of GFAP in EGb761-treated group was lower than that of the model group (P<0.01). Western blot showed that cleaved caspase-3 protein expression in EGb761-treated group at each time point was significantly lower than that in the model group (P<0.01). Western-blot and RT-PCR results showed that the protein and mRNA expression of P-GP and EAAT2 in EGb761-treated group at 15 day and 1 month time points were significant increased than those in the model group (P<0.01). At 2 month time point, which were lower than those in the model group (P<0.01). Conclusion EGb761 can improve the learning and memory ability of VD rats, and regulate the protein and mRNA expression of P-GP and EAAT2 in hippocampus of VD rats at different time points (up-regulated in 1 month and down-regulated in 2 month), and down-regulate the expression of cleaved caspase-3 and GFAP at different time points, thereby delaying the brain damage of VD rats and protecting neurons. Key words: Ginkgo biloba extracts; Vascular dementia rats; P-glycoprotein; Excitatory amino acid transporters 2; Glial fibrillary acidic protein

Application of Tetrode Technology for Analysis of Changes in Neural Excitability of Medial Vestibular Nucleus by Acute Arterial Hypotension

Objectives Excitability o medial vestibular nucleus (MVN) in the brainstem can be affected by changes in the arterial blood pressure. Several animal studies have demonstrated that acute hypotension results in the alteration of multiunit activities and expression of cFos protein in the MVN. In the field of extracellular electrophysiological recording, tetrode technology and spike sorting algorithms can easily identify single unit activity from multiunit activities in the brain. However, detailed properties of electrophysiological changes in single unit of the MVN during acute hypotension have been unknown. Methods Therefore, we applied tetrode techniques and electrophysiological characterization methods to know the effect of acute hypotension on single unit activities of the MVN of rats. Results Twoor3typesofunitcouldbeclassifiedaccordingtothemorphologyofspikes and firing properties of neurons. Acute hypotension elicited 4 types of changes in spontaneous firing of single unit in the MVN. Most of these neurons showed excitatory responses for about within 1 minute after the induction of acute hypotension and then returned to the baseline activity 10 minutes after the injection of sodium nitroprusside. There was also gradual increase in spontaneous firing in some units. In contrast small proportion of units showed rapid reduction of firing rate just after acute hypotension. Conclusions Therefore, application of tetrode technology and spike sorting algorithms is another method for the monitoring of electrical activity of vestibular nuclear during acute hypotension. Keywords: Medial vestibular nucleus; Acute arterial hypotension; Tetrode electrode; Spike sorting; Neuronal firing 중심 단어: ë‚´ì¸¡ì „ì •í•µ, 급성 ì €í˜ˆì••, í ŒíŠ¸ë¡œë“œ ì „ê·¹, 스파이크 분류, ì‹ ê²½ 흥분

Sodium nitroprusside is effective in preventing and/or reversing the development of schizophrenia-related behaviors in an animal model: The SHR strain.

The treatment of schizophrenia with antipsychotics is still unsatisfactory. Therefore, the search for new treatments and prevention is crucial, and animal models are fundamental tools for this objective. Preclinical and clinical data evidence the antipsychotic profile of sodium nitroprusside (SNP), a nitric oxide (NO) donor. We aimed to investigate SNP in treating and/or preventing the schizophrenia-related behaviors presented by the spontaneously hypertensive rats (SHR) strain. Wistar rats (WR) and SHRs were submitted to two schemes of treatment: (i) a single injection of SNP or vehicle in adulthood; (ii) a long-term early treatment from 30 to 60 postnatal day with SNP or vehicle. The following behaviors were evaluated 24hours after the acute treatment or 30days after the long-term treatment: locomotion, social interaction, and contextual fear conditioning. Spontaneously hypertensive rats presented hyperlocomotion, decreased social interaction, and impaired contextual fear conditioning. Single injection of SNP decreased social interaction in both strains and induced a deficit in contextual fear conditioning in WR. Oppositely, early treatment with SNP prevented the behavioral abnormalities in adult SHRs without promoting any effects in WR. Our preclinical data point to SNP as a preventive and safe strategy with a broad range of effectiveness to the positive, negative, and cognitive symptoms of schizophrenia.

Inhibition of overexpression of Giα proteins and nitroxidative stress contribute to sodium nitroprusside-induced attenuation of high blood pressure in SHR.

We earlier showed that vascular smooth muscle cells (VSMC) from spontaneously hypertensive rats (SHR) exhibit enhanced expression of Giα proteins which was attributed to the decreased levels of nitric oxide (NO), because elevation of the intracellular levels of NO by NO donors; sodium nitroprusside (SNP) and S‐Nitroso‐N‐acetyl‐DL‐penicillamine (SNAP), attenuated the enhanced expression of Giα proteins. Since the enhanced expression of Giα proteins is implicated in the pathogenesis of hypertension, the present study was undertaken to investigate if treatment of SHR with SNP could also attenuate the development of high blood pressure (BP) and explore the underlying molecular mechanisms. Intraperitoneal injection of SNP at a concentration of 0.5 mg/kg body weight twice a week for 2 weeks into SHR attenuated the high blood pressure by about 80 mmHg without affecting the BP in WKY rats. SNP treatment also attenuated the enhanced levels of superoxide anion (O2 −), hydrogen peroxide (H2O2), peroxynitrite (ONOO −), and NADPH oxidase activity in VSMC from SHR to control levels. In addition, the overexpression of different subunits of NADPH oxidase; Nox‐1, Nox‐2, Nox‐4, P22phox, and P47phox, and Giα proteins in VSMC from SHR were also attenuated by SNP treatment. On the other hand, SNP treatment augmented the decreased levels of intracellular NO, eNOS, and cGMP in VSMC from SHR. These results suggest that SNP treatment attenuates the development of high BP in SHR through the elevation of intracellular levels of cGMP and inhibition of the enhanced levels of Giα proteins and nitroxidative stress.