Neurobehavioral effects of uremic toxin-indoxyl sulfate in the rat model.

Chronic kidney disease (CKD) is deemed to be a worldwide health concern connected with neurological manifestations. The etiology of central nervous system (CNS) disorders in CKD is still not fully understood, however particular attention is currently being paid to the impact of accumulated toxins. Indoxyl sulfate (IS) is one of the most potent uremic toxins. The purpose of the present study was to assess IS concentrations in the cerebellum, brainstem, cortex, hypothalamus, and striatum with hippocampus of rats chronically exposed to IS. To evaluate IS impact on neurochemical and behavioral alterations, we examined its influence on brain levels of norepinephrine, epinephrine, dopamine, serotonin and their metabolites, as well as changes in behavioral tests (open field test, elevated plus maze test, chimney test, T maze test, and splash test). Our results show the highest IS accumulation in the brainstem. IS leads to behavioral alterations involving apathetic behavior, increased stress sensitivity, and reduced locomotor and exploratory activity. Besides, IS contributes to the impairment of spatial memory and motor coordination. Furthermore, we observed reduced levels of norepinephrine, dopamine or serotonin, mainly in the brainstem. Our findings indicate that IS can be one of the crucial uremic factors responsible for altered mental status in CKD.

Recommendations for the evaluation and management of the anticipated and non-anticipated difficult airway of the Societat Catalana d'Anestesiologia, Reanimació i Terapèutica del Dolor, based on the adaptation of clinical practice guidelines and expert consensus. / Recomendaciones para la evaluación y manejo de la vía aérea difícil prevista y no prevista de la Societat Catalana d'Anestesiologia, Reanimació i Terapèutica del Dolor, basadas en la adaptación de guías de práctica clínica y consenso de expertos.

The Airway Division of the Catalan Society of Anaesthesiology, Intensive Care and Pain Management (SCARTD) presents its latest guidelines for the evaluation and management of the difficult airway. This update includes the technical advances and changes observed in clinical practice since publication of the first edition of the guidelines in 2008. The recommendations were defined by a consensus of experts from the 19 participating hospitals, and were adapted from 5 recently published international guidelines following an in-depth analysis and systematic comparison of their recommendations. The final document was sent to the members of SCARTD for evaluation, and was reviewed by 11 independent experts. The recommendations, therefore, are supported by the latest scientific evidence and endorsed by professionals in the field. This edition develops the definition of the difficult airway, including all airway management techniques, and places emphasis on evaluating and classifying the airway into 3 categories according to the anticipated degree of difficulty and additional safety considerations in order to plan the management strategy. Pre-management planning, in terms of preparing patients and resources and optimising communication and interaction between all professionals involved, plays a pivotal role in all the scenarios addressed. The guidelines reflect the increased presence of video laryngoscopes and second-generation devices in our setting, and promotes their routine use in intubation and their prompt use in cases of unanticipated difficult airway. They also address the increased use of ultrasound imaging as an aid to evaluation and decision-making. New scenarios have also been included, such as the risk of bronchoaspiration and difficult extubation Finally, the document outlines the training and continuing professional development programmes required to guarantee effective and safe implementation of the guidelines.

Differentiations of the effect of NMDA on the spatial learning of rats with 4 and 12 week diabetes mellitus.

This study examines possible interactions between behavioral effects and influence of N-methyl-D-aspartate acid (NMDA) receptors in 4 and 12-week streptozotocin (STZ) induced diabetic rats. Effects of NMDA receptor agonist on spatial learning were tested in control groups of rats and in rats with 4 and 12 weeks diabetes mellitus (DM). Experimental diabetes was induced by a single intravenous injection of streptozotocin at a dose of 65 m/kg, dissolved in citrate buffer. We used the water maze task and examined the acquisition and the retrieval of spatial memory in rats. In our present experiments, we observed that DM had no significant influence on acquisition and retrieval in 4 week diabetic rats on Morris water maze, but impaired examined parameters in 12 week diabetic rats in this test. The NMDA receptor agonist did not influence acquisition but increased recall on water maze in 12 week streptozotocin diabetic rats.

Effect of MPEP in Morris water maze in adult and old rats.

The present investigation assessed the effects of 2-methyl-6-(phenylethynyl)-pyridine (MPEP) on acquisition and reference memory in the Morris water maze in young adult rats aged 3-month and old rats aged 26-month. MPEP reduced the swim speed of the young adult rats during acquisition, shortened the distance they covered and reduced their swim speed in the probe trial. The untreated old rats had impaired acquisition of spatial learning, shortened distance and a lower swim speed in the probe trial in comparison with young rats. MPEP did not influence the activity of the old rats in the water maze. In summary, MPEP did not influence acquisition of spatial learning and reference memory in the young adult and old rats.

Effect of an NMDA receptor agonist on T-maze and passive avoidance test in 12-week streptozotocin-induced diabetic rats.

This study examined behavioral effects mediated by NMDA (N-methyl-D-aspartic acid) receptors in 12-week streptozotocin (STZ)-induced diabetic rats. Effects of an NMDA receptor agonist on behavior in the open field test, passive avoidance test and T-maze were examined in control groups of rats and in rats with diabetes mellitus (DM). We have used 116 rats for experiments. Experimental type I diabetes was induced by a single intravenous injection of streptozotocin at a dose of 65 mg/kg, dissolved in citrate buffer. Stimulation with the NMDA receptor agonist at a dose of 15 mg/kg was performed 30 min before the experiments. In control rats, NMDA increased the number of crossing and rearings in the open field test, improved acquisition and consolidation processes and did not influence recall in the passive avoidance situation and was ineffective in the T-maze. Diabetes significantly inhibited locomotor and exploratory activity and profoundly impaired acquisition, consolidation and recalling in a passive avoidance, and significantly decreased working memory in T-maze. NMDA treatment of diabetic rats significantly improved memory in passive avoidance and T-maze. The NMDA receptor agonist increased locomotor activity in open field test. The obtained results suggested that stimulation of NMDA receptors had beneficial effects on learning and memory in type I diabetic rats.

Antidepressant-like effects of baclofen and LY367385 in the forced swim test in rats.

Baclofen, an agonist of GABA(B) receptors and LY367385, an antagonist of mGluR(1a) receptors, given alone or jointly, reduced the immobility time in the forced swim test but only their separate administration enhanced motility in group of rats without hypoxia. Short-term hypoxia (2% O2, 98% N2, 4 min) did not change the activity of the rats in the forced swim test and it did robustly decrease the motility of these animals. LY367385 reduced the immobility time in the forced swim test but induced locomotion in rats subjected to hypoxia. The obtained results indicated that baclofen and LY367385 given alone or jointly induce an antidepressant-like effect in the forced swim test but only LY367385 possesses such activity in rats that had undergone hypoxia. Both tested ligands are involved in the motility of rats, however, LY367385 influences hypolocomotion hypoxia-induced.

Effects of baclofen and L-AP4 in passive avoidance test in rats after hypoxia-induced amnesia.

Hypoxia-induced cognitive deficits are mainly due to disturbances of the balance between the GABAergic and glutamatergic systems. Acquisition, consolidation and retention impairment in passive avoidance test, hypolocomotion in the open field test, an anxiogenic-like effect in the elevated plus-maze test and hypothermia were observed in rats subjected to hypoxia. Drugs which reduce glutamate release may possess neuroprotective activity. Both, agonists of GABA(B) (baclofen) and group III mGlu receptors (L-AP4) influence the release of glutamate. We studied the behavioral effects of baclofen on hypoxia-induced amnesia and the role of L-AP4 in these processes. Baclofen impaired acquisition, produced an anxiogenic-like effect and lowered body temperature but reduced the hypoxia-induced deficit of acquisition and consolidation of conditioned avoidance, diminished the anxiogenic-like effect, and reduced the motor inhibition produced by hypoxia. L-AP4 improved the acquisition, consolidation and retrieval processes as well as the hypoxia-induced consolidation deficit in the passive avoidance test. Co-administration of baclofen with L-AP4 improved consolidation and enhanced the baclofen activity vs. the respective group without hypoxia. In a group of rats that had undergone hypoxia, joint administration of baclofen and L-AP4 improved retrieval as well as enhanced the effect of baclofen and L-AP4 vs. their respective group without hypoxia. The agonist of group III mGluRs did not change locomotor activity but diminished baclofen-induced motility in rats without hypoxia. L-AP4 given alone or with baclofen produced an anxiogenic-like effect in rats without hypoxia but produced an anxiolytic-like effect in those that had undergone hypoxia. L-AP4 did not influence the activity of baclofen in the elevated plus-maze test. L-AP4 given alone or with baclofen did not change body temperature. It is concluded that baclofen and L-AP4 may cooperate in the consolidation process in rats without hypoxia and in retrieval of passive avoidance in animals that had undergone hypoxia. The observed interaction is probably the result of activation of the presynaptic receptors which influence glutamate and GABA release.

Influence of AIDA on certain behaviors in rats subjected to experimental hypoxia.

The influence of the blockade of group I metabotropic glutamate receptors (mGluRs) by AIDA [(RS)-1-aminoindan-1,5-dicarboxylic acid] on some behavioral effects was tested in control groups of rats and in rats that underwent short-term hypoxia. We used the following methods: the open field test, the passive avoidance test and the elevated "plus" maze test. In rats without hypoxia, AIDA (100 nmol icv) decreased the number of crossings in the open field test, impaired acquisition, improved consolidation and did not influence retrieval in the passive avoidance situation and was ineffective in the elevated "plus" maze. Short-term hypoxia (2% O2, 98% N2), as a model of experimentally induced amnesia, significantly inhibited locomotor and exploratory activity and profoundly impaired acquisition, consolidation and retrieval processes and did not exhibit proanxiogenic or anxiolytic effect in elevated "plus" maze. AIDA (100 nmol icv) used before hypoxia significantly improved consolidation and retrieval processes, but had no effect on acquisition and did not significantly influence all parameters of the elevated "plus" maze test. The obtained results suggest that AIDA, the selective antagonist of group I mGluRs, had beneficial effects on consolidation and retrieval of passive avoidance in rats undergoing hypoxia.

Behavioral effects of the selective blockade of metabotropic glutamate receptor subtype 5 in experimental hypoxia.

The behavioral activity of 2-methyl-6-(phenylethynyl)-pyridine (MPEP), a selective antagonist of metabotropic glutamate receptor subtype 5 (mGluR5), was assesed in control groups of rats and in rats that underwent short-term hypoxia. MPEP applied intravenously (iv) at the dose of 1 mg/kg was tested using the open field test, the passive avoidance test and the elevated "plus" maze test. MPEP significantly increased the number of crossings, rearings and bar approaches in the open field test. It improved the consolidation and retrieval in the passive avoidance situation and did not produce any significant effects in control rats in the elevated "plus" maze test. Hypoxia (2% O2, 98% N2) significantly inhibited locomotor and exploratory activity of rats and also impaired consolidation and retrieval processes, but it did not evoke any changes in the elevated "plus" maze test. MPEP in hypoxia-exposed groups of rats inhibited locomotor and exploratory activity in comparison with MPEP-treated control group. Hypoxia significantly diminished beneficial effect of MPEP on consolidation. In spite of experimental conditions of hypoxia, the effect of MPEP on retrieval was preserved. MPEP used before hypoxia did not significantly influence all parameters of the elevated "plus" maze test. In conclusion, MPEP had beneficial effect on retrieval in hypoxia.