scholarly journals Longitudinal tracing of neurochemical metabolic disorders in working memory neural circuit and optogenetics modulation in rats with vascular cognitive impairment

Author(s):  
Huawei Lin ◽  
Tingting Jin ◽  
Lewen Chen ◽  
Yaling Dai ◽  
Weiwei Jia ◽  
...  

Abstract Objective: Chronic cerebral ischemia leads to vascular cognitive impairment (VCI) that exacerbates along with ischemia time and eventually develops into dementia. Recent advances in molecular neuroimaging contribute to understand its pathological characteristics. We previously traced the anisotropic diffusion of water molecules suggests that chronic cerebral ischemia leads to irreversible progressive damage to white matter integrity. However, the abnormalities of gray matter activity following chronic cerebral ischemia remains not entirely understood.Methods: In this study, in vivo hydrogen proton magnetic resonance spectroscopy (1H-MRS) was applied to longitudinally track the neurochemical metabolic disorder of gray matter associated with working memory, and optogenetics modulation of neurochemical metabolism was performed for targeted treatment of VCI. Results: The results showed that the concentration of N-acetylaspartate (NAA) in the right hippocampus, left hippocampus, right medial prefrontal cortex (mPFC) and mediodorsal thalamus was decreased as early as 7 days after chronic cerebral ischemia, subsequently gamma-aminobutyric acid (GABA) declined whereas myo-inositol (mI) and glutamate (Glu) increased at 14 days, as well as choline (Cho) lost at 28 days, concurrently the change of Glu and GABA in the mPFC and hippocampus was ischemia time-dependent manner within 1 month. Behaviorally, working memory and object recognition memory were impaired at 14 days, 28 days that significantly correlated with neurochemical metabolic disorders. Interestingly, using optogenetics modulation of PV neurons in the mPFC, the metabolic abnormalities of NAA and GABA in working memory neural circuit could be repaired after chronic cerebral ischemia, together with behavior improvements. Conclusions: These findings suggested that as early as 1~4 weeks after chronic cerebral ischemia, the metabolism of NAA, Glu, mI and Cho was synchronously impaired in neural circuit of hippocampus-mediodorsal thalamus-mPFC, and the loss of GABA delayed in the hippocampus, and optogenetics modulation of parvalbumin (PV) neurons in the mPFC can improve the neurochemical metabolism of working memory neural circuit and enhance working memory.

2019 ◽  
Vol 11 (3S) ◽  
pp. 61-67 ◽  
Author(s):  
V. A. Parfenov

The paper reviews the literature on vascular cognitive impairment (VCI), the diagnosis widely used in foreign neurological practice, as well as chronic cerebral ischemia (CCI) and dyscirculatory encephalopathy (DEP), the common diagnoses in Russian neurological practice. According to the etiology, risk factors, and manifestations, Stages I and II DEP largely corresponds to moderate VCI; Stage III DEP does to severe VCI. The results of the author’s studies show that a considerable proportion of patients followed up with a diagnosis of CCI, DEP, have no signs of chronic cerebrovascular disease (CVD), but suffer from primary or secondary headache, vertigo of various origins, emotional disorders, and other diseases. The diagnosis of CCI, DEP should be based on the presence of CCI, the reliable neuroimaging signs of chronic CVD, and the ruling out of other diseases. When treating and preventing VCI, CCI, and DEP, a premium is placed upon both non-drug (regular physical activity, smoking cessation, rational nutrition) and drug therapy aimed at normalizing blood pressure and blood lipid spectrum, preventing blood clots, and improving cognitive functions.


2018 ◽  
Vol 10 (4) ◽  
pp. 139-145 ◽  
Author(s):  
V. A. Parfenov ◽  
S. A. Zhivolupov ◽  
V. V. Zakharov ◽  
L. A. Belova ◽  
O. V. Lagoda ◽  
...  

The paper presents the proceedings of the Round Table with the participation of leading neurologists, which is devoted to chronic cerebrovascular diseases. It is noted that chronic cerebral ischemia (CCI), or dyscirculatory encephalopathy (DEP), is one of the most common neurological diagnoses in our country. The pathogenesis, clinical presentations, diagnosis and treatment of CCI (DEP) and its matching with vascular cognitive impairment (CI), which is regarded in foreign literature as the main manifestation of chronic cerebrovascular disease (CVD) were considered. The authors analyze clinical trials evaluating the efficacy of vinpocetine (Cavinton) in chronic CVD, dizziness, CI, as well as the use of new vinpocetine formulations, such as Cavinton Comforte, in various neurological diseases, dysphagia in particular, in poststroke patients.


Stroke ◽  
2021 ◽  
Vol 52 (2) ◽  
pp. 458-470
Author(s):  
Keera N. Fishman ◽  
Andrea R. Ashbaugh ◽  
Richard H. Swartz

Background and Purpose: Cognitive impairment after stroke, especially executive and attention dysfunction, is common, negatively affects daily functioning, and has limited treatment options. A single-blind, parallel-design, randomized controlled trial was used to examine the impact of goal setting on poststroke cognitive performance. Methods: Stroke survivors (n=72; mean age, 68.38 [SD=11.84] years; 69.4% men) in the chronic phase (≥3 months) after stroke from an academic stroke prevention clinic were randomly assigned to receive goal-setting instructions (n=36) or standard instructions (n=36) after completing baseline cognitive measures of executive function (primary outcome), attention/working memory, verbal learning, and verbal recall. Results: A one-way mixed multivariate analysis of covariance (MANCOVA) found a group by instructional manipulation interaction effect for executive function (Wilks λ=0.66; F [3,66]=11.30; P ≤0.001; η 2 p =0.34), after adjusting for age and years of education. After similar adjustment, attention/working memory (Wilks λ=0.86; F [5,63]=2.10; P =0.043; η 2 p =0.16) and verbal learning ( F [1,60]=5.81; P =0.019; η 2 p =0.09) also showed improvement after instruction but not verbal recall (Wilks λ=0.95; F [1,56]=2.82; P =0.099; η 2 p =0.05). There were no adverse events. Conclusions: Goal setting improved executive function, attention/working memory, and learning in a heterogeneous sample in the chronic phase after stroke. This suggests that >3 months after stroke, vascular cognitive impairment is not a fixed deficit; there is a motivational contributor. Brief treatments targeting goal-oriented behavior and motivation may serve as a novel approach or adjunct treatment to improve cognitive outcomes after stroke. Future research should investigate the use of goal setting on functional outcomes (eg, instrumental activities of daily living and vocational function) in this population, highlighting new potential avenues for treatment for vascular cognitive impairment. Registration: URL: https://www.clinicaltrials.gov . Unique identifier: NCT03511300.


2020 ◽  
Vol 2020 ◽  
pp. 1-11
Author(s):  
Shu Zhu ◽  
Dongyu Min ◽  
Jianhong Zeng ◽  
Yetao Ju ◽  
Yao Liu ◽  
...  

Stem cells from human exfoliated deciduous teeth (SHED) are a unique postnatal stem cell population with high self-renewal ability that originates from the cranial neural crest. Since SHED are homologous to the central nervous system, they possess superior capacity to differentiate into neural cells. However, whether and how SHED ameliorate degenerative central nervous disease are unclear. Chronic cerebral ischemia (CCI) is a kind of neurological disease caused by long-term cerebral circulation insufficiency and is characterized by progressive cognitive and behavioral deterioration. In this study, we showed that either systemic transplantation of SHED or SHED infusion into the hippocampus ameliorated cognitive impairment of CCI rats in four weeks after SHED treatment by rescuing the number of neurons in the hippocampus area. Mechanistically, SHED transplantation decreased the apoptosis of neuronal cells in the hippocampus area of CCI rats through downregulation of cleaved caspase-3. In summary, SHED transplantation protected the neuronal function and reduced neuronal apoptosis, resulting in amelioration of cognitive impairment from CCI. Our findings suggest that SHED are a promising stem cell source for cell therapy of neurological diseases in the clinic.


2021 ◽  
Vol 2 (1) ◽  
pp. 56-61
Author(s):  
Munis Dilshod qizi Fayzieva ◽  
◽  
Durdona Djurabaevna Usmanova

The article presents the results of the analysis of literature sources on chronic cerebral ischemia, etiology and pathogenetic mechanisms of the development of cognitive impairment. In the pathogenesis of chronic cerebral ischemia, systemic and local factors are important, leading to disorders of cerebral hemodynamics, the most adverse effect is exerted by their combination. The most common cause of local disorders of cerebral blood flow is atherosclerotic stenosis and occlusion of intracerebral and extracranial vesselsthat perform transport and distribution functions.Keywords: chronic cerebral ischemia, cognitive disorders, neurological disorders


2016 ◽  
Vol 44 (03) ◽  
pp. 489-514 ◽  
Author(s):  
Yujin Jeon ◽  
Binna Kim ◽  
Jieun E. Kim ◽  
Bori R. Kim ◽  
Soonhyun Ban ◽  
...  

This randomized, double-blind, placebo-controlled trial examined whether the administration of ganglioside, an active ingredient of deer bone extract, can improve working memory performance by increasing gray matter volume and functional connectivity in the default mode network (DMN) in individuals with subjective cognitive impairment. Seventy-five individuals with subjective cognitive impairment were chosen to receive either ganglioside (330[Formula: see text][Formula: see text]g/day or 660[Formula: see text][Formula: see text]g/day) or a placebo for 8 weeks. Changes in working memory performance with treatment of either ganglioside or placebo were assessed as cognitive outcome measures. Using voxel-based morphometry and functional connectivity analyses, changes in gray matter volume and functional connectivity in the DMN were also assessed as brain outcome measures. Improvement in working memory performance was greater in the ganglioside group than in the placebo group. The ganglioside group, relative to the placebo group, showed greater increases in gray matter volume and functional connectivity in the DMN. A significant relationship between increased functional connectivity of the precuneus and improved working memory performance was observed in the ganglioside group. The current findings suggest that ganglioside has cognitive-enhancing effects in individuals with subjective cognitive impairment. Ganglioside-induced increases in gray matter volume and functional connectivity in the DMN may partly be responsible for the potential nootropic effects of ganglioside. The clinical trial was registered with ClinicalTrials.gov (identifier: NCT02379481).


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