Background: Perioperative cerebral hypoperfusion (CH) is common, although the underlying mechanism of cognitive impairment that results due to perioperative cerebral hypoperfusion remains to be determined. Isoflurane anesthesia induces neuronal injury via endoplasmic reticulum (ER) stress, whereas a sub-anesthetic dose of propofol improves postoperative cognitive function. However, the effects of the combination of isoflurane plus propofol, which is a common aesthetic combination administered to patients, on ER stress and cognition remain unknown. Methods: We sought to determine the effects of isoflurane plus propofol on ER stress and cognitive function in rats insulted by cerebral hypoperfusion. Ligation of the bilateral common carotid arteries (CCA) was adopted to develop the cerebral hypoperfusion rat model. A second surgery, open reduction and internal fixation (ORIF), requiring general anesthesia, was performed 30 days later so that the effects of anesthetics on the cognitive function of CH rats could be assessed. Rats received isoflurane alone (1.9%), propofol alone (40 mg•kg −1 •h −1) or a combination of isoflurane and propofol (1% and 20 mg•kg −1 •h −1 or 1.4% and 10 mg•kg −1 •h −1). Behavioral studies (contextual fear conditioning [FC] test), histological analyses (Nissl staining) and biochemical analyses (western blotting of the harvested rat brain tissues) were employed. Results: Hippocampus-dependent memory of rats in group IP 1 (1% isoflurane plus 20 mg•kg −1 •h −1 propofol) was not impaired, and expression level of γ-aminobutyric acid A type receptor α1 subunit, a key cognition-related protein, remained normal. ER stress alleviator, binding immunoglobulin protein, increased extremely while ER stress transcription factor, C/EBP homologous protein, showed no statistical Bu et al. Anesthesia During Perioperative Cerebral Hypoperfusion difference compared with the control group. Numbers of surviving neurons confirmed the substantial neuronal damage caused by propofol or isoflurane alone. Conclusions: These data suggest that ER stress contributes to the underlying mechanism of cognitive impairment and that the combination of isoflurane and propofol did not aggravate cognitive impairment and ER stress in aging rats with CH that were further subjected to ORIF surgery.

Backgrounds : Aging-related impairment of cerebral blood flow regulation leads to the disruption of neuronal micro-environmental homeostasis. Anesthetics should be carefully selected for aging patients since they have less cognition capacity. Effects and mechanisms of propofol or isoflurane have been widely investigated. However, how different combinations of propofol and isoflurane affect neurons and the mechanism still needs to be demonstrated. Methods : We cultured rat hippocampal neurons and established a hypoxic injury model to imitate the micro-environment of aging brains. Three different combinations of propofol and isoflurane were applied to find out an optimum group via Cell Counting Kit-8 (CCK8) assay, lactic acid dehydrogenase (LDH) assay, real-time qPCR, and immunofluorescence of key proteins. Then BiP was silenced by small interfering RNA (siRNA) to explore the mechanism of how isoflurane and propofol affect neurons. Endoplasmic reticulum (ER) stress was measured by Western blot and immunofluorescence. To detect GABA A R α1 subunit proteostasis and its function, real-time qPCR, immunoprecipitation, and Western blot were carried out. Results : Hypoxic neurons showed no different changes on cell viability, LDH leakage, and ER stress after treatment with 1% isoflurane and 1.2 μg/ml of propofol. Hypoxic neurons showed a sharp increase of LDH leakage and ER stress and a decrease of cell viability after treatment with 1.4% isoflurane and 0.6 μg/ml of propofol or 0.5% isoflurane and 1.8 μg/ml of propofol. After knockdown of BiP, the application of 1% isoflurane and 1.2 μg/ml of propofol led to the decrease of GABA A R α1 subunit protein content and viability of cell, as well as aggravation of ER stress. Conclusion : A combination of 1% isoflurane and 1.2 μg/ml of propofol causes the least damage than do other dosages of both two drugs, and endogenous BiP plays an important role in this process.

Background: Perioperative cerebral hypoperfusion often occurs. However, the underlying mechanism and targeted interventions remain mostly to be determined. Anesthetic isoflurane induces neuronal injury via endoplasmic reticulum (ER) stress, whereas sub-anesthetic dose of propofol improves postoperative cognitive function. However, the effects of the combination of isoflurane plus propofol, which is a common combination of anesthesia for patient, on ER stress and the associated cognitive function remain unknown. Methods: We therefore set out to determine the effects of isoflurane plus propofol on the ER stress and cognitive function in the rats insulted by cerebral hypoperfusion. The rats received isoflurane alone (1.9%), propofol alone (40 mg·kg -1 ·h -1 ) or a combination of isoflurane and propofol (1% and 20 mg·kg -1 ·h -1 or 1.4% and 10 mg·kg -1 ·h -1 ). Behavior studies (Fear Conditioning test) and biochemical analyses (Nissl staining and western blotting for the harvested rat brain tissues) were employed in the studies. Results: We found that the combination of 1% isoflurane plus 20 mg·kg -1 ·h -1 propofol attenuated the cerebral hypoperfusion-induced cognitive impairment and the ER stress. Conclusions: These data suggest that ER stress contributes to the underlying mechanism of cognitive impairment and the combination of isoflurane and propofol was able to preserve cognitive function in the rats after cerebral hypoperfusion via prevention of ER stress. These findings have established a system to study the strategy in preventing and treating perioperative cerebral hypoperfusion, leading to promotion of the future larger scale studies.

Background: Perioperative cerebral hypoperfusion often occurs. However, the underlying mechanism of cognitive impairment resulting when perioperative cerebral hypoperfusion occurs remain mostly to be determined. Anesthetic isoflurane induces neuronal injury via endoplasmic reticulum (ER) stress, whereas sub-anesthetic dose of propofol improves postoperative cognitive function. However, the effects of the combination of isoflurane plus propofol, which is a common combination of anesthesia for patient, on ER stress and the associated cognitive function remain unknown. Methods: We therefore set out to determine the effects of isoflurane plus propofol on the ER stress and cognitive function in the rats insulted by cerebral hypoperfusion. In order to get closer to the actual situation in the clinic, high incidence of fracture forces aging people to undergo surgeries needs general anesthesia, we introduce a surgery of tibial fracture with internal fixation to aging rats. The rats received isoflurane alone (1.9%), propofol alone (40 mg·kg-1·h-1) or a combination of isoflurane and propofol (1% and 20 mg·kg-1·h-1 or 1.4% and 10 mg·kg-1·h-1). Behavior studies (Fear Conditioning test), histological analyses (Nissl staining) and biochemical analyses (western blotting for the harvested rat brain tissues) were employed in the studies. Results: We found that the combination of 1% isoflurane plus 20 mg·kg-1·h-1 propofol attenuated the cerebral hypoperfusion-induced cognitive impairment and the ER stress. Conclusions: These data suggest that ER stress contributes to the underlying mechanism of cognitive impairment and the combination of isoflurane and propofol was able to preserve cognitive function in the rats after cerebral hypoperfusion via prevention of ER stress. These findings have established a system to study the strategy in preventing and treating perioperative cerebral hypoperfusion, leading to promotion of the future larger scale studies.

Background: Perioperative cerebral hypoperfusion (CH) is common, although the underlying mechanism of cognitive impairment that results due to perioperative cerebral hypoperfusion remains to be determined. Isoflurane anaesthesia induces neuronal injury via endoplasmic reticulum (ER) stress, whereas a sub-anaesthetic dose of propofol improves postoperative cognitive function. However, the effects of the combination of isoflurane plus propofol, which is a common aesthetic combination administered to patients, on ER stress and cognition remain unknown. Methods: We sought to determine the effects of isoflurane plus propofol on ER stress and cognitive function in rats insulted by cerebral hypoperfusion. Ligation of the bilateral common carotid arteries (CCA) was adopted to develop the cerebral hypoperfusion rat model. A second surgery, open reduction and internal fixation (ORIF), requiring general anaesthesia, was performed 30 days later so that the effects of anaesthetics on the cognitive function of CH rats could be assessed. Rats received isoflurane alone (1.9%), propofol alone (40 mg·kg-1·h-1) or a combination of isoflurane and propofol (1% and 20 mg·kg-1·h-1 or 1.4% and 10 mg·kg-1·h-1). Behavioural studies (fear conditioning [FC] test), histological analyses (Nissl staining) and biochemical analyses (western blotting of the harvested rat brain tissues) were employed. Results: The combination of 1% isoflurane plus 20 mg·kg-1·h-1 propofol did not aggravate cognitive impairment or ER stress in ageing rats with CH that were further subjected ORIF surgery. Conclusions: These data suggest that ER stress contributes to the underlying mechanism of cognitive impairment and that the combination of isoflurane and propofol did not aggravate cognitive impairment and ER stress in ageing rats with CH that were further subjected ORIF surgery.