scholarly journals In Vivo Studies of Protein Misfolding and Neurodegeneration Induced by Metabolic Syndrome Relative to Chronic Cerebral Hypoperfusion: A Critical Review

2020 ◽  
Author(s):  
María I. Herrera ◽  
Juan P. Luaces ◽  
Lucas D. Udovin ◽  
Nicolás Toro-Urrego ◽  
Matilde Otero-Losada ◽  
...  
Keyword(s):  
Metabolic Syndrome ◽  
Cognitive Impairment ◽  
Cerebrovascular Disease ◽  
Protein Misfolding ◽  
Basic Research ◽  
Experimental Models ◽  
Chronic Cerebral Hypoperfusion ◽  
Cerebral Hypoperfusion ◽  
In Vivo Studies

Metabolic syndrome (MetS) leads to microvascular dysfunction and chronic cerebral hypoperfusion (CCH) in an insidious way. Clinical evidence and several rodent models have contributed to determining the neurodegenerative effect of a sustained decrease in cerebral blood flow (CBF). Protein misfolding and aggregation derived from CCH might account for the establishment of vascular cognitive impairment and dementia (VCID) and Alzheimer’s disease (AD). However, the complex and multifactorial etiology of cerebrovascular disease demands the combination of experimental models in scientific research. In this sense, the present work aims at summarizing the differential available rodent paradigms for studying the establishment of cognitive decline resulting from protein misfolding induced by MetS in association with CCH. Revising experimental findings in the field will help further basic research on the pathophysiology of cerebrovascular disease and the future testing of protein-remodeling factors as neuroprotective agents for the prevention of cognitive impairment.

scholarly journals Neuroprotection Targeting Protein Misfolding on Chronic Cerebral Hypoperfusion in the Context of Metabolic Syndrome

2018 ◽  
Vol 12 ◽  
Author(s):  
María I. Herrera ◽  
Lucas D. Udovin ◽  
Nicolás Toro-Urrego ◽  
Carlos F. Kusnier ◽  
Juan P. Luaces ◽  
...  
Keyword(s):  
Metabolic Syndrome ◽  
Protein Misfolding ◽  
Chronic Cerebral Hypoperfusion ◽  
Cerebral Hypoperfusion

scholarly journals TREM-2-p38 MAPK signaling regulates neuroinflammation during chronic cerebral hypoperfusion combined with diabetes mellitus

2020 ◽  
Vol 17 (1) ◽  
Author(s):  
Jiawei Zhang ◽  
Yu Liu ◽  
Yaling Zheng ◽  
Yan Luo ◽  
Yu Du ◽  
...  
Keyword(s):  
Diabetes Mellitus ◽  
Cognitive Impairment ◽  
Inflammatory Response ◽  
P38 Mapk ◽  
High Glucose ◽  
Mapk Signaling ◽  
Chronic Cerebral Hypoperfusion ◽  
Cerebral Hypoperfusion

Abstract Background Diabetes mellitus (DM) and chronic cerebral hypoperfusion(CCH)are both risk factors for cognitive impairment. However, whether DM and CCH can synergistically promote cognitive impairment and the related pathological mechanisms remain unknown. Methods To investigate the effect of DM and CCH on cognitive function, rats fed with high-fat diet (HFD) and injected with low-dose streptozotocin (STZ) followed by bilateral common carotid artery occlusion (BCCAO) were induced to mimic DM and CCH in vivo and mouse BV2 microglial cells were exposed to hypoxia and/or high glucose to mimic CCH complicated with DM pathologies in vitro. To further explore the underlying mechanism, TREM-2-specific small interfering RNA and TREM-2 overexpression lentivirus were used to knock out and overexpress TREM-2, respectively. Results Cognitive deficits, neuronal cell death, neuroinflammation with microglial activation, and TREM-2-MAPK signaling were enhanced when DM was superimposed on CCH both in vivo and in vitro. Manipulating TREM-2 expression levels markedly regulated the p38 MAPK signaling and the inflammatory response in vitro. TREM-2 knockout intensified while TREM-2 overexpression suppressed the p38 MAPK signaling and subsequent pro-inflammatory mediator production under high glucose and hypoxia condition. Conclusions These results suggest that TREM-2 negatively regulates p38 MAPK-mediated inflammatory response when DM was synergistically superimposed on CCH and highlight the importance of TREM-2 as a potential target of immune regulation in DM and CCH.

Cognitive impairment and chronic cerebral hypoperfusion: What can be learned from experimental models

2002 ◽  
Vol 203-204 ◽  
pp. 263-266 ◽  
Author(s):  
Cristina Sarti ◽  
Leonardo Pantoni ◽  
Luciano Bartolini ◽  
Domenico Inzitari
Keyword(s):  
Cognitive Impairment ◽  
Experimental Models ◽  
Chronic Cerebral Hypoperfusion ◽  
Cerebral Hypoperfusion

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

2017 ◽  
Vol 7 (1) ◽  
Author(s):  
Wan li ◽  
Huihui Liu ◽  
Hanjie Jiang ◽  
Chen Wang ◽  
Yongfei Guo ◽  
...  
Keyword(s):  
Cognitive Impairment ◽  
Active Ingredient ◽  
Chronic Cerebral Hypoperfusion ◽  
Cerebral Hypoperfusion

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

2014 ◽  
pp. 95-102 ◽  
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

scholarly journals The Challenging Melanoma Landscape: From Early Drug Discovery to Clinical Approval

Cells ◽  
2021 ◽  
Vol 10 (11) ◽  
pp. 3088
Author(s):  
Mariana Matias ◽  
Jacinta O. Pinho ◽  
Maria João Penetra ◽  
Gonçalo Campos ◽  
Catarina Pinto Reis ◽  
...  
Keyword(s):  
Therapeutic Potential ◽  
Drug Evaluation ◽  
Three Dimensional ◽  
Experimental Models ◽  
In Vivo Studies ◽  
Murine Models ◽  
In Vivo Experiments ◽  
Novel Therapeutic Strategies

Melanoma is recognized as the most dangerous type of skin cancer, with high mortality and resistance to currently used treatments. To overcome the limitations of the available therapeutic options, the discovery and development of new, more effective, and safer therapies is required. In this review, the different research steps involved in the process of antimelanoma drug evaluation and selection are explored, including information regarding in silico, in vitro, and in vivo experiments, as well as clinical trial phases. Details are given about the most used cell lines and assays to perform both two- and three-dimensional in vitro screening of drug candidates towards melanoma. For in vivo studies, murine models are, undoubtedly, the most widely used for assessing the therapeutic potential of new compounds and to study the underlying mechanisms of action. Here, the main melanoma murine models are described as well as other animal species. A section is dedicated to ongoing clinical studies, demonstrating the wide interest and successful efforts devoted to melanoma therapy, in particular at advanced stages of the disease, and a final section includes some considerations regarding approval for marketing by regulatory agencies. Overall, considerable commitment is being directed to the continuous development of optimized experimental models, important for the understanding of melanoma biology and for the evaluation and validation of novel therapeutic strategies.

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

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.

Therapeutic Benefits of Methylene Blue on Cognitive Impairment during Chronic Cerebral Hypoperfusion

2014 ◽  
Vol 42 (s4) ◽  
pp. S525-S535 ◽  
Author(s):  
Allison Auchter ◽  
Justin Williams ◽  
Bryan Barksdale ◽  
Marie H. Monfils ◽  
Francisco Gonzalez-Lima
Keyword(s):  
Methylene Blue ◽  
Cognitive Impairment ◽  
Chronic Cerebral Hypoperfusion ◽  
Cerebral Hypoperfusion ◽  
Therapeutic Benefits

scholarly journals Tripchlorolide May Improve Spatial Cognition Dysfunction and Synaptic Plasticity after Chronic Cerebral Hypoperfusion

2019 ◽  
Vol 2019 ◽  
pp. 1-14 ◽  
Author(s):  
Zhao-Hui Yao ◽  
Xiao-li Yao ◽  
Shao-feng Zhang ◽  
Ji-chang Hu ◽  
Yong Zhang
Keyword(s):  
Cognitive Impairment ◽  
Synaptic Plasticity ◽  
Learning And Memory ◽  
Spatial Learning ◽  
Long Term Potentiation ◽  
Chronic Cerebral Hypoperfusion ◽  
Synaptic Proteins ◽  
Cerebral Hypoperfusion ◽  
Spatial Learning And Memory ◽  
Pathophysiological Mechanism

Chronic cerebral hypoperfusion (CCH) is a common pathophysiological mechanism that underlies cognitive decline and degenerative processes in dementia and other neurodegenerative diseases. Low cerebral blood flow (CBF) during CCH leads to disturbances in the homeostasis of hemodynamics and energy metabolism, which in turn results in oxidative stress, astroglia overactivation, and synaptic protein downregulation. These events contribute to synaptic plasticity and cognitive dysfunction after CCH. Tripchlorolide (TRC) is an herbal compound with potent neuroprotective effects. The potential of TRC to improve CCH-induced cognitive impairment has not yet been determined. In the current study, we employed behavioral techniques, electrophysiology, Western blotting, immunofluorescence, and Golgi staining to investigate the effect of TRC on spatial learning and memory impairment and on synaptic plasticity changes in rats after CCH. Our findings showed that TRC could rescue CCH-induced spatial learning and memory dysfunction and improve long-term potentiation (LTP) disorders. We also found that TRC could prevent CCH-induced reductions in N-methyl-D-aspartic acid receptor 2B, synapsin I, and postsynaptic density protein 95 levels. Moreover, TRC upregulated cAMP-response element binding protein, which is an important transcription factor for synaptic proteins. TRC also prevented the reduction in dendritic spine density that is caused by CCH. However, sham rats treated with TRC did not show any improvement in cognition. Because CCH causes disturbances in brain energy homeostasis, TRC therapy may resolve this instability by correcting a variety of cognitive-related signaling pathways. However, for the normal brain, TRC treatment led to neither disturbance nor improvement in neural plasticity. Additionally, this treatment neither impaired nor further improved cognition. In conclusion, we found that TRC can improve spatial learning and memory, enhance synaptic plasticity, upregulate the expression of some synaptic proteins, and increase the density of dendritic spines. Our findings suggest that TRC may be beneficial in the treatment of cognitive impairment induced by CCH.

Nuclear receptor TLX may be through regulating the SIRT1/NF-κB pathway to ameliorate cognitive impairment in chronic cerebral hypoperfusion

2021 ◽  
Vol 166 ◽  
pp. 142-149
Author(s):  
Chujie Qu ◽  
Changhua Qu ◽  
Linling Xu ◽  
Jun Shen ◽  
Dongwei Lv ◽  
...  
Keyword(s):  
Cognitive Impairment ◽  
Nuclear Receptor ◽  
Chronic Cerebral Hypoperfusion ◽  
Cerebral Hypoperfusion
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