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

2019 ◽  
Author(s):  
Xinyue Bu ◽  
Tang Li ◽  
Haiyun Wang ◽  
Zhengyuan Xia ◽  
Di Guo ◽  
...  
Keyword(s):  
Cognitive Impairment ◽  
Cognitive Function ◽  
Er Stress ◽  
Underlying Mechanism ◽  
Cerebral Hypoperfusion ◽  
Nissl Staining ◽  
Targeted Interventions ◽  
Biochemical Analyses ◽  
Common Combination ◽  
Fear Conditioning Test

Abstract 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.

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

2019 ◽  
Author(s):  
Xinyue Bu ◽  
Tang Li ◽  
Haiyun Wang ◽  
Zhengyuan Xia ◽  
Di Guo ◽  
...  
Keyword(s):  
Cognitive Impairment ◽  
Cognitive Function ◽  
Er Stress ◽  
Underlying Mechanism ◽  
Cerebral Hypoperfusion ◽  
Nissl Staining ◽  
Targeted Interventions ◽  
Biochemical Analyses ◽  
Common Combination ◽  
Fear Conditioning Test

Abstract 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.

scholarly journals 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

2020 ◽  
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 ◽  
Aging Rats ◽  
Biochemical Analyses ◽  
Common Carotid Arteries

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.

scholarly journals 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

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.

scholarly journals Combination of isoflurane and propofol as general anaesthesia during orthopaedic surgery of perioperative cerebral hypoperfusion rats to avoid cognitive impairment Anaesthesia during perioperative cerebral hypoperfusion

2020 ◽  
Author(s):  
Xinyue Bu ◽  
Tang Li ◽  
Haiyun Wang ◽  
Zhengyuan Xia ◽  
Di Guo ◽  
...  
Keyword(s):  
Cognitive Impairment ◽  
Cognitive Function ◽  
Er Stress ◽  
General Anaesthesia ◽  
Carotid Arteries ◽  
Underlying Mechanism ◽  
Cerebral Hypoperfusion ◽  
Nissl Staining ◽  
Biochemical Analyses ◽  
Common Carotid Arteries

Abstract 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.

scholarly journals Shikonin Attenuates Chronic Cerebral Hypoperfusion-Induced Cognitive Impairment by Inhibiting Apoptosis via PTEN/Akt/CREB/BDNF Signaling

2021 ◽  
Vol 2021 ◽  
pp. 1-9
Author(s):  
Yanqiu Jia ◽  
Zhe Li ◽  
Tianjun Wang ◽  
Mingyue Fan ◽  
Jiaxi Song ◽  
...  
Keyword(s):  
Cognitive Impairment ◽  
Signaling Pathway ◽  
Hippocampal Neurons ◽  
Sham Group ◽  
Chronic Cerebral Hypoperfusion ◽  
Cerebral Hypoperfusion ◽  
Terminal Deoxynucleotidyl Transferase ◽  
Vehicle Group ◽  
Nissl Staining ◽  
Bdnf Signaling

Shikonin (SK) exerts neuroprotective effects; however, to date, its protective effect against chronic cerebral hypoperfusion- (CCH-) induced vascular dementia (VaD) has not been investigated. Therefore, the current study investigated whether SK could mitigate the cognitive deficits caused by CCH. The effects of SK treatment on the PTEN/Akt/CREB/BDNF signaling pathway and apoptosis in hippocampal neurons were examined in a rat model of VaD established via bilateral common carotid artery occlusion (BCCAO). Fifty-two rats were randomly divided into 4 groups: sham, vehicle, SK-L (10 mg/kg SK per day), and SK-H (25 mg/kg SK per day). SK was regularly administered by gavage for 2 weeks. The results of the water maze test revealed that the escape latency in the vehicle group was significantly longer than that in the sham group, and rats in the vehicle group spent a smaller proportion of time in the target quadrant than those in the sham group. SK treatment reduced the escape latencies and increased the proportion of time spent in the target quadrant. Nissl staining showed morphological damage in the CA1 areas of the hippocampus in the vehicle group. SK treatment alleviated the injuries to hippocampal neurons. Western blot analysis showed higher p-PTEN and lower p-Akt, p-CREB, and BDNF expression in the vehicle group than in the sham group. SK administration reversed the upregulation of p-PTEN and the downregulation of p-Akt, p-CREB, and BDNF. The number of terminal deoxynucleotidyl transferase-mediated dUTP nick-end labeling- (TUNEL-) positive cells in the hippocampal CA1 region of the vehicle group was significantly increased. Treatment with SK decreased the number of positive cells. Furthermore, as marker proteins of apoptosis, bcl-2 expression was decreased and bax expression was increased; thus, the ratio of bcl-2/bax was decreased in the vehicle group. SK treatment upregulated the expression of bcl-2 and downregulated the expression of bax, thereby elevating the bcl-2/bax ratio. Moreover, the aforementioned effects of SK were dose-dependent. The effect of 25 mg/kg per day was more obvious than that of 10 mg/kg per day. In conclusion, SK inhibited hippocampal neuronal apoptosis to protect against CCH-induced injury by regulating the PTEN/Akt/CREB/BDNF signaling pathway, consequently improving cognitive impairment.

scholarly journals Attenuating vascular stenosis-induced astrogliosis preserves white matter integrity and cognitive function

2021 ◽  
Vol 18 (1) ◽  
Author(s):  
Qian Liu ◽  
Mohammad Iqbal H. Bhuiyan ◽  
Ruijia Liu ◽  
Shanshan Song ◽  
Gulnaz Begum ◽  
...  
Keyword(s):  
Blood Flow ◽  
Cerebral Blood Flow ◽  
Cognitive Impairment ◽  
Cognitive Function ◽  
White Matter ◽  
Spatial Working Memory ◽  
Ex Vivo ◽  
Cerebral Hypoperfusion ◽  
Cellular Mechanisms ◽  
Bilateral Carotid

Abstract Background Chronic cerebral hypoperfusion (CCH) causes white matter damage and cognitive impairment, in which astrogliosis is the major pathology. However, underlying cellular mechanisms are not well defined. Activation of Na+/H+ exchanger-1 (NHE1) in reactive astrocytes causes astrocytic hypertrophy and swelling. In this study, we examined the role of NHE1 protein in astrogliosis, white matter demyelination, and cognitive function in a murine CCH model with bilateral carotid artery stenosis (BCAS). Methods Sham, BCAS, or BCAS mice receiving vehicle or a selective NHE1 inhibitor HOE642 were monitored for changes of the regional cerebral blood flow and behavioral performance for 28 days. Ex vivo MRI-DTI was subsequently conducted to detect brain injury and demyelination. Astrogliosis and demyelination were further examined by immunofluorescence staining. Astrocytic transcriptional profiles were analyzed with bulk RNA-sequencing and RT-qPCR. Results Chronic cerebral blood flow reduction and spatial working memory deficits were detected in the BCAS mice, along with significantly reduced mean fractional anisotropy (FA) values in the corpus callosum, external capsule, and hippocampus in MRI DTI analysis. Compared with the sham control mice, the BCAS mice displayed demyelination and axonal damage and increased GFAP+ astrocytes and Iba1+ microglia. Pharmacological inhibition of NHE1 protein with its inhibitor HOE642 prevented the BCAS-induced gliosis, damage of white matter tracts and hippocampus, and significantly improved cognitive performance. Transcriptome and immunostaining analysis further revealed that NHE1 inhibition specifically attenuated pro-inflammatory pathways and NADPH oxidase activation. Conclusion Our study demonstrates that NHE1 protein is involved in astrogliosis with pro-inflammatory transformation induced by CCH, and its blockade has potentials for reducing astrogliosis, demyelination, and cognitive impairment.

scholarly journals Low oxygen post conditioning improves stroke-induced cognitive impairment

2018 ◽  
Author(s):  
Zidan Zhao ◽  
Lin Kooi Ong ◽  
Giovanni Pietrogrande ◽  
Sonia Sanchez Bezanilla ◽  
Kirby Warren ◽  
...  
Keyword(s):  
Cognitive Impairment ◽  
Cognitive Function ◽  
Learning Task ◽  
Experimental Stroke ◽  
Low Oxygen ◽  
Absolute Level ◽  
Associate Learning ◽  
Air Exposure ◽  
Post Stroke ◽  
Biochemical Analyses

AbstractPost-stroke cognitive impairment has proven to be notoriously difficult to treat. In the current study, we sought to both better understand cellular changes that underpin cognitive deficits and to consider the potential restorative benefits of low oxygen post conditioning (LOPC). We were motivated to use LOPC as an intervention as it is one of the few experimental interventions previously shown to improve cognitive function post-stroke. Experimental stroke was induced by photothrombotic occlusion in adult male C57BL/6 mice. Mice were randomly assigned to either a normal atmospheric air exposure or low oxygen (11% O2) exposure groups three days post-occlusion. On day 17 post-stroke, mice were euthanized for histology or biochemical analyses. Stroked mice exposed to LOPC was associated with marked reductions in amyloid-beta both in its absolute level and in the extent of its oligomerization. Exposure to LOPC post-stroke also improved cellular deficits induced by stroke including an increase in vessel density, a reduction in vascular leakage, and restoration of AQP4 polarisation. Critically, stroked mice exposed to LOPC exhibited robust improvements in cognitive function post-stroke, assessed using a touchscreen based paired- associate learning task. These findings provide compelling pre-clinical evidence of the potential clinical utility of LOPC for enhancing recovery post-stroke.

Curcumin Induces ABCA1 Expression and Apolipoprotein A-I-Mediated Cholesterol Transmembrane in the Chronic Cerebral Hypoperfusion Aging Rats

2013 ◽  
Vol 41 (05) ◽  
pp. 1027-1042 ◽  
Author(s):  
Mingyuan Tian ◽  
Xiong Zhang ◽  
Linhui Wang ◽  
Yu Li
Keyword(s):  
Cognitive Impairment ◽  
Lipoprotein Metabolism ◽  
Hdl Cholesterol ◽  
Vascular Cognitive Impairment ◽  
Vital Role ◽  
Cerebral Hypoperfusion ◽  
Dependent Manner ◽  
Curcumin Treatment ◽  
Nissl Staining ◽  
Abca1 Expression

Cerebral hypoperfusion or aging often results in the disturbances of cholesterol and lipoprotein, which have been well depicted as a common pathological status contributing to neurodegenerative diseases such as vascular dementia (VaD) and Alzheimer's dementia (AD). The pathway of the liver X receptor-β (LXR-β)/retinoic X receptor-α (RXR-α)/ABCA1 plays a vital role in lipoprotein metabolism. Curcumin, a kind of phenolic compound, has been widely used. It has been reported that curcumin can reduce the levels of cholesterol in serum, but the underlying mechanisms are poorly understood. In this study, we evaluated the effects of curcumin on the cholesterol level in brain, vascular cognitive impairment and explored whether the mechanisms for those effects are through activating LXR-β/RXR-α and ABCA1 expression and apoA-I. With a Morris water test, we found that curcumin treatment could attenuate cognitive impairment. With HE and Nissl staining, we found that curcumin could significantly ameliorate the abnormal changes of pyramidal neurons. Meanwhile, the expression of LXR-β, RXR-α, ABCA1 and apoA-I mRNA and protein were increased in a dose-dependent manner after curcumin treatment. Interestingly, both serum HDL cholesterol and total cholesterol levels were statistically higher in the curcumin treatment group than those other groups. We conclude that curcumin has the ability to activate permissive LXR-β/RXR-α signaling and thereby modulate ABCA1 and apoA-I-mediated cholesterol transmembrane transportation, which is a new preventive and therapeutic strategy for cerevascular diseases.

Improvement in cognitive function and cerebral perfusion after bur hole surgery in an adult with moyamoya disease

2011 ◽  
Vol 115 (2) ◽  
pp. 347-349 ◽  
Author(s):  
Lionel Calviere ◽  
Isabelle Catalaa ◽  
Fabienne Marlats ◽  
Anne-Christine Januel ◽  
Jacques Lagarrigue ◽  
...  
Keyword(s):  
Cognitive Impairment ◽  
Cognitive Function ◽  
Mr Imaging ◽  
Cognitive Dysfunction ◽  
Moyamoya Disease ◽  
Cerebral Perfusion ◽  
Cerebral Hypoperfusion ◽  
Complete Regression ◽  
Cerebrovascular Reserve ◽  
Old West

Recent studies have suggested that cognitive impairment may be a common complication in adults with moyamoya disease (MMD). However, the mechanisms of cognitive dysfunction have not been clarified. Whether cognitive impairment may occur as a consequence of cerebral hypoperfusion and may improve after revascularization surgery has not been determined. A 39-year-old West Indian woman with subacute dysexecutive cognitive syndrome and no history of stroke was diagnosed with MMD. Magnetic resonance imaging showed an old, small cerebral infarction in the left frontal white matter and no evidence of recent cerebral ischemia. Perfusion MR imaging with acetazolamide challenge demonstrated a reduced cerebrovascular reserve in both frontal lobes. Revascularization with bur hole surgery was performed, which resulted in complete regression of initial cognitive impairment. Improvement in cognitive function correlated with the development of transdural collaterals on angiography and improvement in cerebral perfusion on MR imaging. This case suggests a relationship between cognitive dysfunction and cerebral hypoperfusion in MMD. Cognitive impairment may be potentially reversible after bur hole surgery and cerebral perfusion improvement.

scholarly journals Inhibition of the Immunoproteasome Subunit LMP7 Ameliorates Cerebral White Matter Demyelination Possibly via TGFβ/Smad Signaling

2021 ◽  
Vol 2021 ◽  
pp. 1-12
Author(s):  
Xingyong Chen ◽  
Nannan Yao ◽  
Zejing Lin ◽  
Yinzhou Wang
Keyword(s):  
Cognitive Impairment ◽  
Cognitive Function ◽  
White Matter ◽  
Growth Factor ◽  
Ischemic Injury ◽  
Chronic Cerebral Hypoperfusion ◽  
Cerebral Hypoperfusion ◽  
Cerebral White Matter ◽  
Smad Signaling ◽  
Bilateral Carotid

Objectives. Chronic cerebral hypoperfusion induces white matter ischemic injury and cognitive impairment, whereas the mechanism remains unclear. Immunoproteasomes have been implicated in the pathogenesis of acute ischemia stroke and multiple sclerosis. However, the expression and role of immunoproteasomes in the brain of chronic cerebral hypoperfusion remain to be clarified. Methods. Chronic white matter ischemic injury mice models were induced by bilateral carotid artery stenosis (BCAS). A selective immunoproteasome subunit low-molecular-mass peptide-7 (LMP7) inhibitor PR957 was administered to mice. Cognitive function, white matter integrity, and potential pathways were assessed after BCAS. Results. The present study found that chronic cerebral hypoperfusion following BCAS induced cerebral white matter demyelination and cognitive impairment, accompanied with elevated expression of the immunoproteasomes LMP2 and LMP7, activation of astrocytes and microglia, and increased production of inflammatory cytokines (e.g., interleukin-1β (IL-1β), tumor necrosis factor-α (TNF-α), IL-10, transforming growth factor-β1 (TGFβ1), and insulin-like growth factor-1 (IGF-1)). However, inhibition of LMP7 with the specific proteasome inhibitor PR957 significantly mitigated the histological damage of the white matter, suppressed inflammatory response, and paralleled by an improvement of cognitive function. Furthermore, treatment of PR957 significantly upregulated the level of TGFβ1, the total expression level, and the phosphorylation level of Smad2/3 and promoted brain remyelination. Surprisingly, PR957 alone had no effects on the neuroinflammation response and the activation of TGFβ/Smad signaling in the sham-operated (BCAS-nonoperated) mice. Conclusions. The possible mechanism underlying this was attributed to that the immunoproteasome regulates TGFβ/Smad signaling-mediated neuroinflammation and oligodendrocyte remyelination.

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