scholarly journals Effects ofFructus mumeExtract on MAPK and NF-κB Signaling and the Resultant Improvement in the Cognitive Deficits Induced by Chronic Cerebral Hypoperfusion

2012 ◽  
Vol 2012 ◽  
pp. 1-13 ◽  
Author(s):  
Won Kyung Jeon ◽  
Jinhua Ma ◽  
Bo-Ryoung Choi ◽  
Seol-Heui Han ◽  
Qinghao Jin ◽  
...  
Keyword(s):  
Microglial Activation ◽  
Molecular Mechanisms ◽  
Therapeutic Potential ◽  
Artery Occlusion ◽  
Chronic Cerebral Hypoperfusion ◽  
Mitogen Activated Protein Kinase ◽  
Daily Administration ◽  
Cerebral Hypoperfusion ◽  
Memory Impairments ◽  
The Status

Fructus mume(F. mume) has been used as a medicinal food in Japan and has been reported to have anti-inflammatory effects in inflammatory bowel disease and macrophage-mediated inflammation. We investigated the effects ofF. mumeextracts on cognitive dysfunction in rats with chronic cerebral hypoperfusion and the molecular mechanisms underlying these effects. Chronic cerebral hypoperfusion was induced in male Wister rats by bilateral common artery occlusion (BCCAo). Daily administration ofF. mumeextracts was started on day 20 after post-BCCAo and continued for 40 days. The status of hippocampus-dependent memory was evaluated in control rats, rats with chronic cerebral hypoperfusion, and rats with chronic cerebral hypoperfusion that were administeredF. mume. The levels of microglial activation were measured in the hippocampus and the fimbria of hippocampus, and expression levels of hippocampal mitogen-activated protein kinase (MAPK) and nuclear factor-κB (NF-κB) were examined. Rats that received chronic cerebral hypoperfusion showed spatial memory impairments relative to the control rats; these impairments were reduced by daily administration ofF. mume. Administration ofF. mumemitigated the microglial activation and alterations of hippocampal MAPK and NF-κB signaling in the rats with chronic cerebral hypoperfusion. These results indicate thatF. mumemay possess therapeutic potential for the prevention of vascular dementia via inhibition of inflammatory processes.

scholarly journals URB597 protects against NLRP3 inflammasome activation by inhibiting autophagy dysfunction in a rat model of chronic cerebral hypoperfusion

2019 ◽  
Vol 16 (1) ◽  
Author(s):  
Shao-Hua Su ◽  
Yi-Fang Wu ◽  
Qi Lin ◽  
Da-Peng Wang ◽  
Jian Hai
Keyword(s):  
Proinflammatory Cytokines ◽  
Rat Model ◽  
Nlrp3 Inflammasome ◽  
Therapeutic Potential ◽  
Artery Occlusion ◽  
Chronic Cerebral Hypoperfusion ◽  
Cerebral Hypoperfusion ◽  
Ultrastructural Changes ◽  
Inflammasome Activation ◽  
Related Proteins

Abstract Background Previous studies reported that URB597 (URB) had therapeutic potential for treating chronic cerebral hypoperfusion (CCH)-induced neuroinflammation and autophagy dysfunction. However, the interaction mechanisms underlying the CCH-induced abnormal excessive autophagy and neuroinflammation remain unknown. In this study, we investigated the roles of impaired autophagy in nucleotide-binding oligomerization domain-like receptor family pyrin domain-containing (NLRP) 3 inflammasome activation in the rat hippocampus and the underlying mechanisms under the condition of induced CCH as well as the effect of URB treatment. Methods The CCH rat model was established by bilateral common carotid artery occlusion (BCCAo), and rats were randomly divided into 11 groups as follows: (1) sham-operated, (2) BCCAo; (3) BCCAo+autophagy inhibitor 3-methyladenine (3-MA), (4) BCCAo+lysosome inhibitor chloroquine (CQ), (5) BCCAo+microglial activation inhibitor minocycline, (6) BCCAo+ROS scavenger N-acetylcysteine (NAC), (7) BCCAo+URB, (8) BCCAo+URB+3-MA, (9) BCCAo+URB+CQ, (10) BCCAo+URB+minocycline, (11) BCCAo+URB+NAC. The cell localizations of LC3, p62, LAMP1, TOM20 and NLRP3 were assessed by immunofluorescence staining. The levels of autophagy-related proteins (LC3, p62, LAMP1, BNIP3 and parkin), NLRP3 inflammasome-related proteins (NLRP3, CASP1 and IL-1β), microglial marker (OX-42) and proinflammatory cytokines (iNOS and COX-2) were evaluated by western blotting, and proinflammatory cytokines (IL-1β and TNF-a) were determined by ELISA. Reactive oxygen species (ROS) were assessed by dihydroethidium staining. The mitochondrial ultrastructural changes were examined by electron microscopy. Results CCH induced microglial overactivation and ROS accumulation, promoting the activation of the NLRP3 inflammasome and the release of IL-1β. Blocked autophagy and mitophagy flux enhanced the activation of the NLRP3-CASP1 inflammasome pathway. However, URB alleviated impaired autophagy and mitophagy by decreasing mitochondrial ROS and microglial overactivation as well as restoring lysosomal function, which would further inhibit the activation of the NLRP3-CASP1 inflammasome pathway. Conclusion These findings extended previous studies indicating the function of URB in the mitigation of chronic ischemic injury of the brain.

scholarly journals Acupuncture Rescues Cognitive Impairment and Upregulates Dopamine-β-Hydroxylase Expression in Chronic Cerebral Hypoperfusion Rats

2018 ◽  
Vol 2018 ◽  
pp. 1-8 ◽  
Author(s):  
Ling-Yong Xiao ◽  
Jing-Wen Yang ◽  
Xue-Rui Wang ◽  
Yang Ye ◽  
Na-Na Yang ◽  
...  
Keyword(s):  
Long Term Potentiation ◽  
Artery Occlusion ◽  
Carotid Artery Occlusion ◽  
Chronic Cerebral Hypoperfusion ◽  
Cerebral Hypoperfusion ◽  
Vessel Occlusion ◽  
Memory Impairments ◽  
Beneficial Effects ◽  
Hippocampus Dependent Memory

Alteration of dopamine (DA) and noradrenaline (NA) contributes to cognitive function. Acupuncture has been shown to affect DA and NA in chronic cerebral hypoperfusion (CCH) rats. However, the effect of acupuncture on DA-β-hydroxylase (DBH), the biosynthetic enzyme of NA, remains unknown. In CCH rats we established chronic hypoperfusion by bilateral common carotid artery occlusion (two-vessel occlusion, 2VO) and treated them with acupuncture. Acupuncture displayed beneficial effects on hippocampus-dependent memory impairments, including nonspatial and spatial memory. That is also reflected in hippocampus long-term-potentiation (LTP). Moreover, DBH expression in the hippocampus and DBH activity in cerebrospinal fluid were upregulated after acupuncture treatment. In conclusion, these in vivo findings suggest that acupuncture exerts a therapeutic effect on hippocampus-dependent memory and hippocampus LTP in CCH rats, which may be partially related to the modulation of DBH in the hippocampus.

scholarly journals Electroacupuncture Attenuates Cognitive Impairment in Rat Model of Chronic Cerebral Hypoperfusion via miR-137/NOX4 Axis

2021 ◽  
Vol 2021 ◽  
pp. 1-10
Author(s):  
Xiaochen Bi ◽  
Yanfei Feng ◽  
Zemin Wu ◽  
Jianqiao Fang
Keyword(s):  
Oxidative Stress ◽  
Neuronal Apoptosis ◽  
Molecular Mechanisms ◽  
Artery Occlusion ◽  
Chronic Cerebral Hypoperfusion ◽  
Cerebral Hypoperfusion ◽  
Control Group ◽  
Spatial Learning And Memory ◽  
Protective Effects ◽  
And Oxidative Stress

Electroacupuncture has shown protective effects on cognitive decline. However, the underlying molecular mechanisms are not clear. The present study was conducted to determine whether the cognitive function was ameliorated in cerebral hypoperfusion rats following electroacupuncture and to investigate the role of miR-137/NOX4 axis. In this study, chronic cerebral hypoperfusion (CCH) model was established by bilateral common carotid artery occlusion. Electroacupuncture treatment attenuated brain injury in CCH model group via regulating miR-137/NOX4 axis. Furthermore, the data of neuronal apoptosis and oxidative stress were observed. Our findings indicated that (1) neuronal apoptosis and oxidative stress in CCH rats were significantly increased compared with control group; (2) the animal cognitive performance was evaluated using the Morris water maze (MWM). The results showed that electroacupuncture therapy ameliorated spatial learning and memory impairment in cerebral hypoperfusion rats; and (3) electroacupuncture therapy reduces neuronal apoptosis and oxidative stress by activating miR-137/NOX4 axis. These results suggest that electroacupuncture therapy for CCH may be mediated by miR-137/NOX4 axis. Electroacupuncture therapy may act as a potential therapeutic approach for chronic cerebral hypoperfusion.

scholarly journals Contribution of p38 MAPK to the Ameliorating Effect of Enriched Environment on the Cognitive Deficits Induced by Chronic Cerebral Hypoperfusion

2016 ◽  
Vol 40 (3-4) ◽  
pp. 549-557 ◽  
Author(s):  
Yu-Wang Li ◽  
Qing-Yun Li ◽  
Jin-Hua Wang ◽  
Xiao-Lin Xu
Keyword(s):  
P38 Mapk ◽  
Cognitive Deficits ◽  
Mapk Signaling ◽  
Selective Inhibitor ◽  
Enriched Environment ◽  
Chronic Cerebral Hypoperfusion ◽  
Mitogen Activated Protein Kinase ◽  
Cerebral Hypoperfusion ◽  
Memory Impairments ◽  
Mitogen Activated Protein

Background/Aims: An enriched environment (EE) ameliorates learning and memory impairments induced by chronic cerebral hypoperfusion, and the p38 mitogen-activated protein kinase (p38 MAPK) signaling pathway exerts both beneficial and deleterious effects on the nervous system during the progression of ischemia. Methods: The present study investigated whether p38 MAPK participates in the process by which EE exposure ameliorates the cognitive deficits induced by chronic cerebral hypoperfusion. Results: EE exposure significantly enhanced the cognitive performance of vascular dementia (VD) model rats, and p38 MAPK protein decreased in parallel with cognitive improvements. Inhibition of p38 MAPK function by its selective inhibitor SB203580 improved the cognition index of VD rats and upregulated p38 MAPK expression with p38 MAPK antisense oligodeoxynucleotides. This impaired cognition in VD rats could not be rescued by EE exposure. Conclusion: p38 MAPK participates in the process by which EE exposure ameliorates cognitive deficits induced by chronic cerebral hypoperfusion.

Effect of endogenous sulfur dioxide on spatial learning and memory and hippocampal damages in the experimental model of chronic cerebral hypoperfusion

2020 ◽  
Vol 31 (3) ◽  
Author(s):  
Elaheh Ghasemi ◽  
Faezeh Afkhami Aghda ◽  
Mohammad Ebrahim Rezvani ◽  
Azadeh Shahrokhi Raeini ◽  
Zeynab Hafizibarjin ◽  
...  
Keyword(s):  
Oxidative Stress ◽  
Sulfur Dioxide ◽  
Tissue Damage ◽  
Neuronal Damage ◽  
Artery Occlusion ◽  
Carotid Artery Occlusion ◽  
Vital Role ◽  
Chronic Cerebral Hypoperfusion ◽  
Cerebral Hypoperfusion ◽  
Spatial Learning And Memory

AbstractBackgroundThe vascular changes due to cerebrovascular damage, especially on the capillaries, play a vital role in causing vascular dementia. Increasing oxidative stress can lead to tissue damage while reducing brain blood flow. The use of factors reducing the oxidative stress level can decrease the brain damages. Sulfur dioxide (SO2) is one of the most important air pollutants that lead to the development of severe brain damage in large quantities. However, studies have recently confirmed the protective effect of SO2 in cardiac ischemic injury, atherosclerosis and pulmonary infections.MethodsThe permanent bilateral common carotid artery occlusion (BCAO) method was used to induce chronic cerebral hypoperfusion (CCH). Two treatment groups of SO2 were studied. The animal cognitive performance was evaluated using the Morris water maze. Hippocampal tissue damage was examined after 2 months of BCAO. In the biochemical analysis, the activity of catalase and lipid peroxidation of the hippocampus was studied.ResultsNeuronal damage in hippocampus, as well as cognitive impairment in ischemia groups treated with SO2 showed a significant improvement. Catalase activity was also significantly increased in the hippocampus of treated groups.ConclusionsAccording to the results, SO2 is likely to be effective in reducing the CCH-caused damages by increasing the antioxidant capacity of the hippocampus.

scholarly journals Alternations of Septal-hippocampal System in the Adult Wistar Rat with Spatial Memory Impairments Induced by Chronic Cerebral Hypoperfusion

2011 ◽  
Vol 20 (2) ◽  
pp. 92-99 ◽  
Author(s):  
Bo-Ryoung Choi ◽  
Kyoung Ja Kwon ◽  
Seung Hwa Park ◽  
Won Kyung Jeon ◽  
Seol-Heui Han ◽  
...  
Keyword(s):  
Spatial Memory ◽  
Wistar Rat ◽  
Chronic Cerebral Hypoperfusion ◽  
Cerebral Hypoperfusion ◽  
Memory Impairments

Vitexin regulates EPAC and NLRP3 and ameliorates chronic cerebral hypoperfusion injury

2021 ◽  
Author(s):  
Qilong Zhang ◽  
Zhijia Fan ◽  
wei xue ◽  
Fanfan Sun ◽  
Huaqing Zhu ◽  
...  
Keyword(s):  
Neuronal Damage ◽  
Critical Factor ◽  
Underlying Mechanism ◽  
Cerebrovascular Diseases ◽  
Artery Occlusion ◽  
Chronic Cerebral Hypoperfusion ◽  
Cerebral Hypoperfusion ◽  
Protective Effects ◽  
Ht22 Cells

Chronic cerebral hypoperfusion (CCH), as a critical factor of chronic cerebrovascular diseases, has greatly influenced the health of patients with vascular dementia (VD). The putative protective effects of vitexin on the CCH need further investigations. In the current study, the role of vitexin and its underlying mechanism were investigated with permanent bilateral common carotid artery occlusion (2VO) in rats as well as HT22 cells with OGD/R injury model. The results demonstrated that vitexin improved cognitive dysfunction as well as alleviated pathological neuronal damage in HE and TUNEL results. The decreased levels of Epac1, Epac2, Rap1 and p-ERK were reversed by vitexin in rats with CCH. Furthermore, this study indicated that vitexin alleviated CCH-induced inflammation injuries by reducing the expression of NLRP3, Caspase-1, IL-1β, IL-6, and cleaved Caspase-3. In vitro, vitexin increased the expression of Epac1 and Epac2, decreased the activation of the NLRP3-mediated inflammation, and improved cell viability. Taken together, our findings suggest that vitexin can reduce the degree of the progressing pathological damage in the cortex and hippocampus and inhibit further deterioration of cognitive function in rats with CCH. Epac and NLRP3 can be regulated by vitexin, which provides enlightenment for the protection of CCH injury.

scholarly journals Electroacupuncture Improved Chronic Cerebral Hypoperfusion-Induced Anxiety-Like Behavior and Memory Impairments in Spontaneously Hypertensive Rats by Downregulating the ACE/Ang II/AT1R Axis and Upregulating the ACE2/Ang-(1-7)/MasR Axis

2020 ◽  
Vol 2020 ◽  
pp. 1-12 ◽  
Author(s):  
Peipei Feng ◽  
Zemin Wu ◽  
Hao Liu ◽  
Yafang Shen ◽  
Xu Yao ◽  
...  
Keyword(s):  
Angiotensin Ii ◽  
Angiotensin Converting Enzyme ◽  
Spontaneously Hypertensive Rats ◽  
Chronic Cerebral Hypoperfusion ◽  
Cerebral Hypoperfusion ◽  
Ang Ii ◽  
Converting Enzyme ◽  
Hypertensive Rats ◽  
Spontaneously Hypertensive ◽  
Memory Impairments

Electroacupuncture (EA) can effectively alleviate anxiety disorders and memory impairments caused by various neurodegenerative diseases; however, the molecular mechanisms underlying its neuroprotective effects are unclear. Previous studies have shown that the renin-angiotensin system (RAS) comprises of two axes with mutual antagonism: the classical angiotensin converting enzyme/angiotensin II/angiotensin II type 1 receptor (ACE/Ang II/AT1R) axis and the protective angiotensin converting enzyme 2/angiotensin-(1-7)/Mas receptor (ACE2/Ang-(1-7)/MasR) axis. In this study, we observed that chronic cerebral hypoperfusion (CCH) mediated anxiety-like behavior and memory impairments in spontaneously hypertensive rats (SHR) via upregulation of the hippocampal classical axis (ACE/Ang II/AT1R) and the partial hippocampal protective axis (ACE2/Ang-(1-7)). However, Ang II levels were much higher than those of Ang-(1–7), indicating that the ACE/Ang II/AT1R axis plays a dominant role in the comorbidity of CCH and hypertension. Moreover, candesartan cilexetil (Canc) and perindopril (Peril) were used as positive control drugs. We found that EA, Canc, and Peril attenuated CCH-induced anxiety-like behavior and memory impairments in SHR, potentially via downregulation of the hippocampal classical axis (ACE/Ang II/AT1R) and upregulation of the whole hippocampal protective axis (ACE2/Ang-(1-7)/MasR). These results suggest that EA therapy for CCH with hypertension may be mediated by two hippocampal RAS axes.

scholarly journals Characterization of Tauopathy in a Rat Model of Post-Stroke Dementia Combining Acute Infarct and Chronic Cerebral Hypoperfusion

2020 ◽  
Vol 21 (18) ◽  
pp. 6929
Author(s):  
Dong Bin Back ◽  
Bo-Ryoung Choi ◽  
Jung-Soo Han ◽  
Kyoung Ja Kwon ◽  
Dong-Hee Choi ◽  
...  
Keyword(s):  
Ischemic Stroke ◽  
Cognitive Impairment ◽  
Acute Ischemic Stroke ◽  
Rat Model ◽  
Artery Occlusion ◽  
Chronic Cerebral Hypoperfusion ◽  
Cerebral Hypoperfusion ◽  
Tau Hyperphosphorylation ◽  
Post Stroke

Post-stroke dementia (PSD) is a major neurodegenerative consequence of stroke. Tauopathy has been reported in diverse neurodegenerative diseases. We investigated the cognitive impairment and pathomechanism associated with tauopathy in a rat model of PSD by modeling acute ischemic stroke and underlying chronic cerebral hypoperfusion (CCH). We performed middle cerebral artery occlusion (MCAO) surgery in rats to mimic acute ischemic stroke, followed by bilateral common carotid artery occlusion (BCCAo) surgery to mimic CCH. We performed behavioral tests and focused on the characterization of tauopathy through histology. Parenchymal infiltration of cerebrospinal fluid (CSF) tracers after intracisternal injection was examined to evaluate glymphatic function. In an animal model of PSD, cognitive impairment was aggravated when BCCAo was combined with MCAO. Tauopathy, manifested by tau hyperphosphorylation, was prominent in the peri-infarct area when CCH was combined. Synergistic accentuation of tauopathy was evident in the white matter. Microtubules in the neuronal axon and myelin sheath showed partial colocalization with the hyperphosphorylated tau, whereas oligodendrocytes showed near-complete colocalization. Parenchymal infiltration of CSF tracers was attenuated in the PSD model. Our experimental results suggest a hypothesis that CCH may aggravate cognitive impairment and tau hyperphosphorylation in a rat model of PSD by interfering with tau clearance through the glymphatic system. Therapeutic strategies to improve the clearance of brain metabolic wastes, including tau, may be a promising approach to prevent PSD after stroke.

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