No abstract

Background: The mechanisms of emergence from general anesthesia remain to be elucidated. Recent studies indicate that the central histaminergic system plays a critical role in maintaining wakefulness. In addition, the neural pathways that regulate the wake-sleep cycle are involved in general anesthesia. In this study, we determined the role of the central histaminergic system in emergence from propofol anesthesia using microinjections and single-unit recordings in rats.Methods: All rats were implanted with unilateral guide cannulae or bilateral cannulae. Return of righting reflex could be used as an index of recovery of consciousness in rats. Neuronal activity was collected. The placement of the injection cannulae and/or microelectrodes was verified in coronal sections (10 μm) cut with a cryostat microtome. Animals with incorrect placements were removed from this study. The neuronal activity was subjected to an off-line clustering analysis (K-means) using the Plexon Off-line Sorter to identify one or more individual units recorded from the same electrode from each other and noise.Results: We found intracerebroventricular (icv) microinjections of histamine decreased the emergence time in a dose-dependent manner and had an excitatory effect on the firing activity of medial prefrontal cortex (mPFC) neurons, while the decrease of emergence time was completely reversed by the pre-treatment with triprolidine (80 μg/5 μL) but not cimetidine (100 μg/5 μL). Moreover, the presumed histaminergic neurons fired in a state-dependent manner, and there was a dramatic increase in firing activity before regain of righting reflex. Furthermore, bidirectional manipulations of emergence were achieved through the microinjection of gamma-aminobutyric acid (GABA) (10 μg/side) and a potent H3 receptor inverse agonist ciproxifan (1 μg/side) into the posterior hypothalamus, where the tuberomammillary nucleus (TMN) resides. Combine the behavioral and neurophysiologic evidence, the central histaminergic system promotes emergence from propofol anesthesia in rats.Conclusions: Our findings suggest an important role of the central histaminergic system in a broader field of state transitions, such as emergence from propofol anesthesia.

BackgroundHypothermia is an effective method of reducing brain injury caused by a variety of neurological insults. It is aimed to elucidate whether a change in the expression of PERK‐mediated pathway proteins is an indicator of the neuroprotective effect of mild hypothermia after cerebral ischaemia/reperfusion.MethodsOne hundred and ninety‐two male C57BL/6 mice were randomly divided into three groups: a sham group, a cerebral normothermic ischaemia/reperfusion (I/R) group and a cerebral hypothermic I/R group. A cerebral ischaemia model was established by ligating the bilateral common carotid artery for 15 min. Mice in the hypothermia group stayed in a cage that was set at 33°C, sprayed with a spray of 70% ethanol, and blown with two high‐speed fans. The state of neurons was assessed on micropreparations stained with haematoxylin–eosin and TUNEL. The expressions of GRP78, p‐perk, p‐eif2α, ATF4 and CHOP were measured by western blot analysis 6, 12, 24 and 72 h after reperfusion.ResultsThe number of surviving cells was significantly higher in the hypothermia group than in the group without hypothermia (p < .05). The GRP78 expression in the hypothermia group was statistically higher (p < .05) than in the ischaemia/reperfusion group. Optical densities of p‐perk, p‐eif2α and ATF4 in hippocampus CA1 neurons ischaemia were statistically significantly lower in the hypothermia group than in the ischaemia/reperfusion group (p < .05). The CHOP expression in the hypothermia group was statistically lower (p < .05) than in the ischaemia/reperfusion group.ConclusionMild hypothermia for 6 h promoted moderate neuroprotection by mediating the expression of GRP78, p‐PERK, p‐eIF2α, ATF4 and CHOP.

Background: The mechanisms of emergence from general anesthesia remain to be elucidated. Recent studies indicate that the central histaminergic system plays a critical role in maintaining wakefulness. Methods: Role of the central histaminergic system in emergence from propofol anesthesia using microinjections and single-unit recordings in rats was evaluated. Results: Intracerebroventricular (icv) microinjections of histamine decreased the emergence time in a dose-dependent manner and had an excitatory effect on the firing activity of medial prefrontal cortex (mPFC) neurons, while the decrease of emergence time was completely reversed by the pre-treatment with triprolidine (80 μg/5 μl) but not cimetidine (100 μg/5 μl). Moreover, the presumed histaminergic neurons fired in a state-dependent manner, and there was a dramatic increase in firing activity before regain of righting reflex. Furthermore, bidirectional manipulations of emergence were achieved through the microinjection of GABA (10 μg/side) and a potent H3 receptor inverse agonist ciproxian (1 μg/side) into the posterior hypothalamus, where the tuberomammillary nucleus (TMN) resides. Conclusion: Combining the behavioral and neurophysiologic evidence, the central histaminergic system promotes emergence from propofol anesthesia in rats. Our findings suggest an important role of the central histaminergic system in a broader field of state transitions, such as emergence from propofol anesthesia.