Combination of Isoflurane and Propofol as General Anesthesia During Orthopedic Surgery of Perioperative Cerebral Hypoperfusion Rats to Avoid Cognitive Impairment

Abstract 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. A ligation of bilateral common carotid arteries (CCA) surgery was adopted to prepare rats as cerebral hypoperfusion (CH) animal model. A second surgery, open reduction and internal fixation (ORIF), requiring general anesthesia, was operated 30 days later so that the effects of anesthetics on cognitive function of these CH rats could be assessed. 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 propol did not aggravate the cognitive impairment and the ER stress in aging rats with cerebral hypoperusion and being subjected to an ORIF surgery. Conclusions: These data suggest that ER stress contributes to the underlying mechanism of cognitive impairment and the combination of isoflurane and propofol did not aggravate the cognitive impairment and the ER stress in aging rats with cerebral hypoperfusion and being subjected to an ORIF surgery.

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Combination of isoflurane and propofol, a means for general anesthesia in the orthopedic surgery of perioperative cerebral hypoperfusion rats to avoid cognitive impairment Anesthesia of perioperative cerebral hypoperfusion

10.21203/rs.2.14325/v3 ◽

2019 ◽

Author(s):

Xinyue Bu ◽

Tang Li ◽

Haiyun Wang ◽

Zhengyuan Xia ◽

Di Guo ◽

...

Keyword(s):

Cognitive Impairment ◽

Cognitive Function ◽

Er Stress ◽

General Anesthesia ◽

Underlying Mechanism ◽

Cerebral Hypoperfusion ◽

Nissl Staining ◽

High Incidence ◽

Biochemical Analyses ◽

Aging People

Abstract 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.

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Intradialytic Cerebral Hypoperfusion as Mechanism for Cognitive Impairment in Patients on Hemodialysis

Journal of the American Society of Nephrology ◽

10.1681/asn.2019050461 ◽

2019 ◽

Vol 30 (11) ◽

pp. 2052-2058 ◽

Cited By ~ 7

Author(s):

Dawn F. Wolfgram

Keyword(s):

Cognitive Impairment ◽

Cerebral Perfusion ◽

Ischemic Injury ◽

Hemodialysis Patients ◽

Cognitive Outcomes ◽

Cerebral Injury ◽

Cerebral Hypoperfusion ◽

Increased Risk ◽

Cerebral Ischemic Injury ◽

Cerebral Ischemic

The high frequency of cognitive impairment in individuals on hemodialysis is well characterized. In-center hemodialysis patients are disproportionately affected by cognitive impairment compared with other dialysis populations, identifying hemodialysis itself as a possible factor. The pathophysiology of cognitive impairment has multiple components, but vascular-mediated cerebral injury appears to contribute based on studies demonstrating increased cerebral ischemic lesions and atrophy in brain imaging of patients on hemodialysis. Patients on hemodialysis may be at increased risk for cerebral ischemic injury disease due to vasculopathy associated with ESKD and from their comorbid diseases, such as hypertension and diabetes. This review focuses on the intradialytic cerebral hypoperfusion that can occur during routine hemodialysis due to the circulatory stress of hemodialysis. This includes a review of current methods used to monitor intradialytic cerebral perfusion and the structural and functional cognitive outcomes that have been associated with changes in intradialytic cerebral perfusion. Monitoring of intradialytic cerebral perfusion may become clinically relevant as nephrologists try to avoid the cognitive complications seen with hemodialysis. Identifying the appropriate methods to assess risk for cerebral ischemic injury and the relationship of intradialytic cerebral hypoperfusion to cognitive outcomes will help inform the decision to use intradialytic cerebral perfusion monitoring in the clinical setting as part of a strategy to prevent cognitive decline.

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Intranasal insulin rescues repeated anesthesia-induced deficits in synaptic plasticity and memory and prevents apoptosis in neonatal mice via mTORC1

Scientific Reports ◽

10.1038/s41598-021-94849-3 ◽

2021 ◽

Vol 11 (1) ◽

Author(s):

Patricia Soriano Roque ◽

Mehdi Hooshmandi ◽

Laura Neagu-Lund ◽

Shelly Yin ◽

Noosha Yousefpour ◽

...

Keyword(s):

Cognitive Impairment ◽

Synaptic Plasticity ◽

General Anesthesia ◽

Preventive Treatment ◽

Intranasal Insulin ◽

Translational Repressor ◽

Beneficial Effects ◽

Underlying Mechanisms ◽

Induced Apoptosis ◽

Preclinical And Clinical Studies

AbstractLong-lasting cognitive impairment in juveniles undergoing repeated general anesthesia has been observed in numerous preclinical and clinical studies, yet, the underlying mechanisms remain unknown and no preventive treatment is available. We found that daily intranasal insulin administration to juvenile mice for 7 days prior to repeated isoflurane anesthesia rescues deficits in hippocampus-dependent memory and synaptic plasticity in adulthood. Moreover, intranasal insulin prevented anesthesia-induced apoptosis of hippocampal cells, which is thought to underlie cognitive impairment. Inhibition of the mechanistic target of rapamycin complex 1 (mTORC1), a major intracellular effector of insulin receptor, blocked the beneficial effects of intranasal insulin on anesthesia-induced apoptosis. Consistent with this finding, mice lacking mTORC1 downstream translational repressor 4E-BP2 showed no induction of repeated anesthesia-induced apoptosis. Our study demonstrates that intranasal insulin prevents general anesthesia-induced apoptosis of hippocampal cells, and deficits in synaptic plasticity and memory, and suggests that the rescue effect is mediated via mTORC1/4E-BP2 signaling.

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Cannabinoid receptor agonist WIN55,212-2 and fatty acid amide hydrolase inhibitor URB597 may protect against cognitive impairment in rats of chronic cerebral hypoperfusion via PI3K/AKT signaling

Behavioural Brain Research ◽

10.1016/j.bbr.2016.07.009 ◽

2016 ◽

Vol 313 ◽

pp. 334-344 ◽

Cited By ~ 24

Author(s):

Shao-Hua Su ◽

Yue-Qing Wang ◽

Yi-Fang Wu ◽

Da-Peng Wang ◽

Qi Lin ◽

...

Keyword(s):

Cognitive Impairment ◽

Fatty Acid ◽

Receptor Agonist ◽

Cannabinoid Receptor ◽

Fatty Acid Amide Hydrolase ◽

Acid Amide ◽

Akt Signaling ◽

Cerebral Hypoperfusion ◽

Amide Hydrolase ◽

Fatty Acid Amide

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Is Childhood General Anesthesia Exposure An Etiological Contributor to Cognitive Impairment?

Science Insights ◽

10.15354/si.21.re005 ◽

2021 ◽

Vol 36 (3) ◽

pp. 251-259

Author(s):

Yi Tian ◽

Peiyu Liu ◽

Weisong Liu ◽

Qiaojing Xu ◽

Xiangkun Zhao

Keyword(s):

Risk Factors ◽

Early Childhood ◽

Cognitive Impairment ◽

General Anesthesia ◽

Strong Correlation ◽

Clinical Studies ◽

Clinical Evidence ◽

Preclinical Studies ◽

Invasive Procedures ◽

Immature Brain

General anesthesia is necessary for patients to undergo surgery and invasive procedures. However, numerous preclinical studies have demonstrated widespread developmental neurotoxicity of the commonly used anesthetics and sedatives for the immature brain. Clinical studies also suggest a strong correlation between childhood anesthesia exposure and subsequent behavioral or cognitive impairment in adulthood. These findings have attracted increasing attention of anesthesiologists, pediatricians, and caregivers about the safety of anesthesia exposure in children, especially during early childhood. Herein, the aim of this review was to present the molecular mechanism of general anesthesia and its effects on the developing brain and introduce the recent clinical evidence of changes in cognition function post-childhood general anesthesia exposure. More importantly, some of the spots will be importantly discussed to scrutinize the phenomena; only in this way, it may help minimize or eliminate relevant risk factors.

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(S)-Oxiracetam is the Active Ingredient in Oxiracetam that Alleviates the Cognitive Impairment Induced by Chronic Cerebral Hypoperfusion in Rats

Scientific Reports ◽

10.1038/s41598-017-10283-4 ◽

2017 ◽

Vol 7 (1) ◽

Cited By ~ 10

Author(s):

Wan li ◽

Huihui Liu ◽

Hanjie Jiang ◽

Chen Wang ◽

Yongfei Guo ◽

...

Keyword(s):

Cognitive Impairment ◽

Active Ingredient ◽

Chronic Cerebral Hypoperfusion ◽

Cerebral Hypoperfusion

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A Mouse Model of Chronic Cerebral Hypoperfusion Characterizing Features of Vascular Cognitive Impairment

Methods in Molecular Biology - Cerebral Angiogenesis ◽

10.1007/978-1-4939-0320-7_8 ◽

2014 ◽

pp. 95-102 ◽

Cited By ~ 13

Author(s):

Masafumi Ihara ◽

Akihiko Taguchi ◽

Takakuni Maki ◽

Kazuo Washida ◽

Hidekazu Tomimoto

Keyword(s):

Cognitive Impairment ◽

Mouse Model ◽

Vascular Cognitive Impairment ◽

Chronic Cerebral Hypoperfusion ◽

Cerebral Hypoperfusion

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Dl-3-n-Butylphthalide Alleviates Hippocampal Neuron Damage in Chronic Cerebral Hypoperfusion via Regulation of the CNTF/CNTFRα/JAK2/STAT3 Signaling Pathways

Frontiers in Aging Neuroscience ◽

10.3389/fnagi.2020.587403 ◽

2021 ◽

Vol 12 ◽

Author(s):

Wenxian Li ◽

Di Wei ◽

Zheng Zhu ◽

Xiaomei Xie ◽

Shuqin Zhan ◽

...

Keyword(s):

Cognitive Impairment ◽

Signaling Pathways ◽

Neuronal Death ◽

Neuronal Apoptosis ◽

Vascular Cognitive Impairment ◽

Chronic Cerebral Hypoperfusion ◽

Cerebral Hypoperfusion ◽

Stat3 Pathway ◽

Stat3 Signaling

Chronic cerebral hypoperfusion (CCH) contributes to cognitive impairments, and hippocampal neuronal death is one of the key factors involved in this process. Dl-3-n-butylphthalide (D3NB) is a synthetic compound originally isolated from the seeds of Apium graveolens, which exhibits neuroprotective effects against some neurological diseases. However, the protective mechanisms of D3NB in a CCH model mimicking vascular cognitive impairment remains to be explored. We induced CCH in rats by a bilateral common carotid artery occlusion (BCCAO) operation. Animals were randomly divided into a sham-operated group, CCH 4-week group, CCH 8-week group, and the corresponding D3NB-treatment groups. Cultured primary hippocampal neurons were exposed to oxygen-glucose deprivation/reperfusion (OGD/R) to mimic CCH in vitro. We aimed to explore the effects of D3NB treatment on hippocampal neuronal death after CCH as well as its underlying molecular mechanism. We observed memory impairment and increased hippocampal neuronal apoptosis in the CCH groups, combined with inhibition of CNTF/CNTFRα/JAK2/STAT3 signaling, as compared with that of sham control rats. D3NB significantly attenuated cognitive impairment in CCH rats and decreased hippocampal neuronal apoptosis after BCCAO in vivo or OGD/R in vitro. More importantly, D3NB reversed the inhibition of CNTF/CNTFRα expression and activated the JAK2/STAT3 pathway. Additionally, JAK2/STAT3 pathway inhibitor AG490 counteracted the protective effects of D3NB in vitro. Our results suggest that D3NB could improve cognitive function after CCH and that this neuroprotective effect may be associated with reduced hippocampal neuronal apoptosis via modulation of CNTF/CNTFRα/JAK2/STAT3 signaling pathways. D3NB may be a promising therapeutic strategy for vascular cognitive impairment induced by CCH.

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