General Anesthesia In Rats Research Articles

Effects of propofol and halothane on long-term potentiation in the rat hippocampus after transient cerebral ischaemia

Propofol is reported to have protective effects on cerebral ischaemia-induced neuronal death. The aim of this study was to explore whether propofol and halothane can protect hippocampal neuronal function from ischaemic injury during general anaesthesia in rats. Rats were divided into 2-vessel occlusion (incomplete cerebral ischaemia) and 4-vessel occlusion (complete cerebral ischaemia) groups consisting of three subgroups each (sham-operated, propofol and halothane groups). One hour after starting propofol 1 mg kg(-1) min(-1) with 30% O2 and N2 or halothane 0.8% in 30% O2 and N2 rats with or without bilateral vertebral artery occlusion had bilateral common carotid arteries occluded by vessel clips for 10 min. Anaesthesia was maintained for another 1 h. Seven days after ischaemia-reperfusion, hippocampal long-term potentiation in the perforant path-dentate gyrus synapse was determined as an index of cerebral outcome. In the propofol groups, the formation of long-term potentiation was significantly impaired in the 2-vessel and 4-vessel occlusion groups compared to the respective sham-operated groups (P < 0.01 and P < 0.05, respectively). Impaired formation of long-term potentiation in propofol groups was comparable to that in halothane groups. The formation of long-team potentiation in the propofol and halothane 2-vessel group was not significantly different from that in the awake 2-vessel group. Propofol and halothane administered during ischaemia do not possess protective effects against hippocampal neuronal dysfunction induced by cerebral ischaemia-reperfusion as evaluated by our transient ischaemic rat models.

Altered hippocampal gene expression 2 days after general anesthesia in rats

We profiled changes in gene expression in the hippocampus 2 days after a 4 h general anesthetic with isoflurane and nitrous oxide. Eighteen month old Fisher 344 rats were anesthetized for 4 h with 1.2% isoflurane and 70% nitrous oxide ( N = 9) whereas control rats breathed 30% oxygen for 4 h ( N = 9). Rats were sacrificed 48 h later and RNA extracted from the hippocampus for gene expression profiling. Three gene arrays were used per group, with samples prepared by pooling RNA from three rats. Differentially expressed genes were analyzed based on a weighted error statistical model. Microarray results for 6 differentially expressed genes were verified with reverse transcriptase polymerase chain reaction. Compared to unanesthetized controls, 297 genes were differentially expressed 2 days following anesthesia ( P < 0.05). Of these, 113 are named genes; 64% were up-regulated and 36% were down-regulated. The majority of differentially expressed genes are implicated in cell stress and replication, signal transduction, transcription, protein biosynthesis, cell structure, and metabolism. The correlation between fold changes on array and reverse transcriptase polymerase chain reaction was good ( R 2 = 0.85) for the 6 genes examined with both methods. These results demonstrate that in rats general anesthesia is associated with persistent changes in hippocampal gene expression, suggesting that recovery of the brain from anesthesia is considerably slower than generally recognized.

Quantified EEG analysis monitoring in a novel model of general anaesthesia in rats

The aim of this research was to evaluate the safety and reliability of an anaesthetic mixture (Equitensine: pentobarbital, chloral hydrate, dihydroxypropane, ethanol) which, unlike other ‘classic’ anaesthetics, such as ketamine [ The Electroencephalogram in Anaesthesia, Springer, Berlin, 1984], has been demonstrated not to induce alterations in the extracellular concentrations of cerebral excitatory amino acids. Quantified EEG analysis monitoring and behavioural observation were used to quantify the degree and the time course of the changes in cerebral electrical activity, analgesia and sedation induced, in rats, by the compound under investigation. Equitensine (0.33 ml/100 g), administered intraperitoneally, induced analgesia (monitored by the tail flick method) for 60–70 min and a pattern of behavioural sedation (loss of the righting reflex) lasting, on average, 130–150 min. The EEG monitoring revealed a pattern typical of burst suppression which lasted 15–20 min, followed by another, lasting 270–300 min, characterized by slow waves of high amplitude. The quantified EEG analysis demonstrated that the changes in cerebral electrical activity lasted longer than behavioural observation suggested. The compound under examination was found to be safe, reliable and non-invasive to administer and sustain in all the animals, and quantified EEG analysis proved to be a very sensitive method for highlighting the functional changes in the central nervous system.

Experimental spinal cord injury: effect of a calcium channel antagonist (nicardipine).

Variable benefits from the use of a number of calcium channel blockers in experimental spinal cord injury have been reported. To our knowledge, these agents have not been previously tested in a contusion model of cord injury in which neurological outcome is one of the critical outcome parameters. We carried out preliminary behavioral toxicity testing to identify a range of low, moderate, and high dosage levels of the calcium channel blocker, nicardipine; these dosage levels were to be used subsequently in formal testing. After laminectomy at T8 under general anesthesia in rats, a 10-g weight was dropped from a height of 5 cm onto the spinal cord. The animals were randomly assigned to four groups: control or one of three nicardipine treatment groups: (a) low dose (1 mg/kg, followed by a continuous 23-hour infusion of 0.5 mg/kg/hour), (b) moderate dose (10 mg/kg, followed by 5 mg/kg/hour for 23 hours, and (c) high dose (20 mg/kg, followed by 23-hour infusion of 10 mg/kg/hour). Functional recovery was tested over the course of 4 weeks with the Tarlov scale, the inclined plane, and a sensory-motor battery of tests (combined behavioral score). After sacrifice at 4 weeks, morphometric analysis of residual gray and white matter was performed at the epicenter of the spinal cord injury. Statistical analysis of the behavioral data failed to reveal any differences among the control or nicardipine treatment groups. The morphometric analysis similarly failed to show differences between the control and any treatment group.(ABSTRACT TRUNCATED AT 250 WORDS)