The Effect of Long-Term Environmental Enrichment in Chronic Cerebral Hypoperfusion-Induced Memory Impairment in Rats

2016 ◽  
Vol 19 (3) ◽  
pp. 278-286 ◽  
Author(s):  
Jong-Min Park ◽  
Ho-Hyun Seong ◽  
Han-Byeol Jin ◽  
Youn-Jung Kim
Keyword(s):  
Cognitive Impairment ◽  
Vascular Dementia ◽  
Cognitive Functions ◽  
Environmental Enrichment ◽  
Nursing Intervention ◽  
Chronic Cerebral Hypoperfusion ◽  
Cerebral Hypoperfusion ◽  
Vegf Expression ◽  
Y Maze

Vascular dementia (VaD) is the second most common cause of dementia. It occurs when the cerebral blood supply is reduced by disarrangement of the circulatory system. Environmental enrichment (EE) has been associated with cognitive improvement, motor function recovery, and anxiety relief with respect to various neurodegenerative diseases and emotional stress models. The purpose of this study was to determine whether long-term EE influenced cognitive impairment in a rat model of chronic hypoperfusion induced by permanent occlusion of bilateral common carotid arteries (BCCAo). The Y-maze and Morris water maze tests were performed to evaluate the rats’ cognitive functions. Also, the protein expression of brain-derived neurotrophic factor (BDNF), phosphorylated cAMP-calcium response element binding protein (pCREB), and vascular endothelial growth factor (VEGF) were confirmed by Western blot. The microvessels and angiogenesis-associated proteins in the hippocampal region were investigated using immunohistochemistry. The VaD + EE group showed significantly better cognitive functions than the VaD group in both the Y-maze and MWM tests. In addition, the VaD + EE group showed significantly increased expression of BDNF, pCREB, and VEGF in the hippocampus compared to the VaD group. Rats in the VaD + EE group also had increased length of microvessels and VEGF expression in the hippocampus. These results suggest that long-term EE exerts neuroprotective effects against cognitive impairment induced by chronic cerebral hypoperfusion through the enhancement of BDNF, pCREB, and VEGF expression and indicate that EE may be a good nursing intervention in vascular dementia patients.

scholarly journals AIM2 Inflammasome Mediates Hallmark Neuropathological Alterations and Cognitive Impairment in a Mouse Model of Vascular Dementia

2020 ◽  
Author(s):  
Luting Poh ◽  
David Y. Fann ◽  
Peiyan Wong ◽  
Hong Meng Lim ◽  
Sok Lin Foo ◽  
...  
Keyword(s):  
Cognitive Impairment ◽  
Mouse Model ◽  
Vascular Dementia ◽  
Cell Activation ◽  
Memory Loss ◽  
Neuronal Loss ◽  
Brain Regions ◽  
Chronic Cerebral Hypoperfusion ◽  
Cerebral Hypoperfusion ◽  
Glial Cell Activation

AbstractChronic cerebral hypoperfusion is associated with vascular dementia (VaD). Cerebral hypoperfusion may initiate complex molecular and cellular inflammatory pathways that contribute to long-term cognitive impairment and memory loss. Here we used a bilateral common carotid artery stenosis (BCAS) mouse model of VaD to investigate its effect on the innate immune response – particularly the inflammasome signaling pathway. Comprehensive analyses revealed that chronic cerebral hypoperfusion induces a complex temporal expression and activation of inflammasome components and their downstream products (IL-1β and IL-18) in different brain regions, and promotes activation of apoptotic and pyroptotic cell death pathways. Polarized glial cell activation, white matter lesion formation and hippocampal neuronal loss also occurred in a spatiotemporal manner. Moreover, in AIM2 knockout mice we observed attenuated inflammasome-mediated production of proinflammatory cytokines, apoptosis and pyroptosis, as well as resistance to chronic microglial activation, myelin breakdown, hippocampal neuronal loss, and behavioural and cognitive deficits following BCAS. Hence, we have demonstrated that activation of the AIM2 inflammasome substantially contributes to the pathophysiology of chronic cerebral hypoperfusion-induced brain injury and may therefore represent a promising therapeutic target for attenuating cognitive impairment in VaD.

scholarly journals NXP031 Improves Cognitive Impairment in a Chronic Cerebral Hypoperfusion-Induced Vascular Dementia Rat Model through Nrf2 Signaling

2021 ◽  
Vol 22 (12) ◽  
pp. 6285
Author(s):  
Jae-Min Lee ◽  
Joo-Hee Lee ◽  
Min-Kyung Song ◽  
Youn-Jung Kim
Keyword(s):  
Oxidative Stress ◽  
Cognitive Impairment ◽  
Vitamin C ◽  
Vascular Dementia ◽  
Brain Regions ◽  
Artery Occlusion ◽  
Vital Role ◽  
Chronic Cerebral Hypoperfusion ◽  
Dna Aptamer ◽  
Cerebral Hypoperfusion

Vascular dementia (VaD) is a progressive cognitive impairment caused by a reduced blood supply to the brain. Chronic cerebral hypoperfusion (CCH) is one cause of VaD; it induces oxidative stress, neuroinflammation, and blood-brain barrier (BBB) disruption, damaging several brain regions. Vitamin C plays a vital role in preventing oxidative stress-related diseases induced by reactive oxygen species, but it is easily oxidized and loses its antioxidant activity. To overcome this weakness, we have developed a vitamin C/DNA aptamer complex (NXP031) that increases vitamin C’s antioxidant efficacy. Aptamers are short single-stranded nucleic acid polymers (DNA or RNA) that can interact with their corresponding target with high affinity. We established an animal model of VaD by permanent bilateral common carotid artery occlusion (BCCAO) in 12 week old Wistar rats. Twelve weeks after BCCAO, we injected NXP031 into the rats intraperitoneally for two weeks at moderate (200 mg/4 mg/kg) and high concentrations (200 mg/20 mg/kg). NXP031 administration alleviates cognitive impairment, microglial activity, and oxidative stress after CCH. NXP031 increased the expression of basal lamina (laminin), endothelial cell (RECA-1, PECAM-1), and pericyte (PDGFRβ); these markers maintain the BBB integrity. We found that NXP031 administration activated the Nrf2-ARE pathway and increased the expression of SOD-1 and GSTO1/2. These results suggest that this new aptamer complex, NXP031, could be a therapeutic intervention in CCH-induced VaD.

Exploring the Role of Remote Ischemic Preconditioning In Long Term Cognitive Impairment after Global Ischemia-Reperfusion-Induced Vascular Dementia in Mice

2020 ◽  
Author(s):  
Amteshwar Singh Jaggi
Keyword(s):  
Cognitive Impairment ◽  
Cerebral Ischemia ◽  
Vascular Dementia ◽  
Ischemic Preconditioning ◽  
Ischemia Reperfusion ◽  
Remote Ischemic Preconditioning ◽  
Global Cerebral Ischemia ◽  
Cerebral Ischemic ◽  
The Brain

Aim: The aim of the present study is to explore the neuroprotective effects of remote ischemic preconditioning in long term cognitive impairment after global cerebral ischemia induced-vascular dementia in mice. Material and methods: The mice were subjected to global cerebral ischemia by occluding the bilateral common carotid arteries for 12 minutes followed by the 24 hours of the reperfusion. The remote ischemic preconditioning stimulus was delivered in the form of 4 cycles of ischemia/reperfusion for 5 minutes each. The cerebral ischemic injury induced-long term cognitive impairment-related learning and memory alterations was assessed using morris water maze, the motor performances of the animals were evaluated using rota-rod test and neurological severity score. The cerebral infract size of the brain were quantified using triphenyltetrazolium chloride staining. Results: Global cerebral ischemia causes long term memory impairment, decreases motor performances and increases the brain infract size in animals. The delivery of remote ischemic preconditioning stimulus significantly abolished the long-term cognitive impairment and ameliorates the motor performances as well as cerebral infract size in brain. Conclusion: The remote ischemic preconditioning mediates neuro protection against global cerebral ischemic injury induced long-term cognitive impairment.

scholarly journals Depletion of acetate-producing bacteria from the gut microbiota facilitates cognitive impairment through the gut-brain neural mechanism in diabetic mice

Microbiome ◽  
2021 ◽  
Vol 9 (1) ◽  
Author(s):  
Hong Zheng ◽  
Pengtao Xu ◽  
Qiaoying Jiang ◽  
Qingqing Xu ◽  
Yafei Zheng ◽  
...  
Keyword(s):  
Cognitive Impairment ◽  
Gut Microbiota ◽  
Cognitive Functions ◽  
Neural Mechanism ◽  
Fecal Microbiota ◽  
Protective Role ◽  
Fecal Microbiota Transplant ◽  
Memory Impairments ◽  
The Impact

Abstract Background Modification of the gut microbiota has been reported to reduce the incidence of type 1 diabetes mellitus (T1D). We hypothesized that the gut microbiota shifts might also have an effect on cognitive functions in T1D. Herein we used a non-absorbable antibiotic vancomycin to modify the gut microbiota in streptozotocin (STZ)-induced T1D mice and studied the impact of microbial changes on cognitive performances in T1D mice and its potential gut-brain neural mechanism. Results We found that vancomycin exposure disrupted the gut microbiome, altered host metabolic phenotypes, and facilitated cognitive impairment in T1D mice. Long-term acetate deficiency due to depletion of acetate-producing bacteria resulted in the reduction of synaptophysin (SYP) in the hippocampus as well as learning and memory impairments. Exogenous acetate supplement or fecal microbiota transplant recovered hippocampal SYP level in vancomycin-treated T1D mice, and this effect was attenuated by vagal inhibition or vagotomy. Conclusions Our results demonstrate the protective role of microbiota metabolite acetate in cognitive functions and suggest long-term acetate deficiency as a risk factor of cognitive decline.

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.

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