Abstract WP491: HUCBC Treatment Promotes White Matter Remodeling and Improves Glymphatic Function and Cognitive Outcome in Rats With Vascular Dementia

Stroke ◽  
2020 ◽  
Vol 51 (Suppl_1) ◽  
Author(s):  
Poornima Venkat ◽  
Alex Zacharek ◽  
Michael Chopp ◽  
Jieli Chen
Keyword(s):  
White Matter ◽  
Vascular Dementia ◽  
Cognitive Outcome ◽  
Discrimination Index ◽  
Male Rats ◽  
Morris Water Maze Test ◽  
Therapeutic Effects ◽  
Term Memory ◽  
Test Discrimination ◽  
The Brain

Aim: Vascular Dementia (VaD) accounts for nearly 20% of all dementia. We have investigated the therapeutic effects of human umbilical cord blood cells (HUCBCs) treatment of VaD and tested mechanisms such as that white matter (WM) remodeling and glymphatic function that contribute to improving cognitive outcome. Methods: Male rats (6-8m old) were subjected to a multiple microinfarct model (MMI, 500-800 cholesterol crystals injected into the internal carotid artery) of VaD, and 3 days later treated with PBS or HUCBC (5х10 6 , i.v.) n=6/group. Cognitive tests were conducted and rats sacrificed at 28 days after MMI. To evaluate glymphatic function, fluorescent tracers (Texas Red dextran, MW: 3 kD and FITC-dextran, MW: 500 kD) were injected into the cisterna magna over 30min at 14 days after MMI. Rats (6/group/time point) were sacrificed at 30min, 3h, and 6h and tracer movement analyzed using laser scanning confocal microscopy. Results: HUCBC treatment significantly improves short term memory (Novel object recognition test discrimination index: MMI: 35.6±3.6%; MMI+HUCBC: 74.2±4.3%; p<0.0001), long term memory (odor test discrimination index: MMI: 49.9±5.8%; MMI+HUCBC: 69.2±4.8%; p<0.01) and spatial learning and memory (Morris water maze test: decreased latency and increased % of time in target quadrant, p<0.05) compared to control MMI rats. HUCBC treatment significantly increases axon and myelin density, increases oligodendrocyte and oligodendrocyte progenitor cells number, and increases Synaptophysin expression in the brain compared to control MMI rats. HUCBC treatment of MMI in rats significantly improves glymphatic function by reversing MMI induced delay in cerebrospinal fluid penetration into the brain parenchyma via paravascular pathways as well as delayed waste clearance from the brain. HUCBC treatment significantly decreases serum protein expression of BACE1, S100, MCP-1, and TGF-β which may contribute to HUCBC induced therapeutic effects. Conclusions: HUCBC treatment of an MMI rat model of VaD promotes WM remodeling, anti-inflammatory effects and improves glymphatic function which in concert may contribute to the improvement in cognition and memory. Thus, HUCBC treatment warrants further investigation as a potential therapy for VaD.

scholarly journals The Prophylactic and Therapeutic Effects of Fermented Cordyceps sinensis Powder, Cs-C-Q80, on Subcortical Ischemic Vascular Dementia in Mice

2018 ◽  
Vol 2018 ◽  
pp. 1-10
Author(s):  
Ying Chen ◽  
Lifeng Fu ◽  
Min Han ◽  
Meiying Jin ◽  
Jiaying Wu ◽  
...  
Keyword(s):  
Object Recognition ◽  
White Matter ◽  
Vascular Dementia ◽  
Morris Water Maze ◽  
Water Maze ◽  
Interleukin 1 ◽  
Cordyceps Sinensis ◽  
Morris Water Maze Test ◽  
Therapeutic Effects ◽  
Therapeutic Treatment

Corbrin Capsule, a preparation of Cordyceps sinensis analogue, is a pleiotropic traditional Chinese patent medicine with the main component of fermentative cordyceps fungus powder (Cs-C-Q80). The neuroprotective effects of Cs-C-Q80, as a substitution of Cordyceps sinensis, have not been fully identified. The objectives of this study were to explore the prophylactic and therapeutic effects of Cs-C-Q80 in vascular dementia mice model. The efficacy of Cs-C-Q80 was investigated in a molecular level as well. The subcortical ischemic vascular dementia was modelled by permanent right unilateral common carotid arteries occlusion (rUCCAO) in adult male mice. The animals were randomly divided and treated by gavage with vehicle (1% CMC-Na solution) (rUCCAO model) or Cs-C-Q80 powder at 0.2 g/kg or 1.0 g/kg, respectively. Preventive treatment was administrated by gavage daily for 7 days before rUCCAO, while therapeutic treatment was administrated continuously from 28 days after rUCCAO. Object recognition test and Morris water maze test were performed to evaluate the learning and working memory. The luxol fast blue stain (Kluver-Barrera method) and immunohistochemistry for myelin basic protein (MBP) were employed to determine the severity of white matter damage. Both preventive and therapeutic treatment with Cs-C-Q80 protected against the rUCCAO-induced memory impair in mice as determined by object recognition and Morris water maze tests. The histopathological analyses revealed significant white matter rarefaction and reduction of MBP expression in corpus callosum after rUCCAO, which could be counteracted by either preventive or therapeutic treatment with Cs-C-Q80. Moreover, the Cs-C-Q80 treatments inhibited rUCCAO-induced astrocytes activation and the tumor necrosis factor α (TNF-α) and interleukin-1β expression, indicating the anti-inflammatory roles of Cs-C-Q80 against subcortical ischemia. Cs-C-Q80 is a potential preparation for the prophylaxis and treatment of subcortical ischemic vascular dementia. The underlying pharmacological efficacy might be associated with suppression of myelin degeneration, glia activation, and inflammatory cytokines release.

Humanin-S14G Ameliorates Vascular Dementia Through Regulating miR-134

2021 ◽  
Vol 11 (4) ◽  
pp. 743-748
Author(s):  
Yuan Zhuang ◽  
Xutang Wang
Keyword(s):  
Vascular Dementia ◽  
Cognitive Ability ◽  
Sham Group ◽  
Learning Ability ◽  
Male Rats ◽  
Morris Water Maze Test ◽  
Bdnf Expression ◽  
Neuroprotective Effects ◽  
Synthetic Derivative ◽  
The Brain

Humanin-S14G is a synthetic derivative of Humanin with neuroprotective effects. miR-134 involves in the regulation of the nervous system. However, whether Humanin-S14G ameliorates VD through miR-134 remains poorly understood. Healthy male rats were assigned into sham group; VD group and Humanin-S14G group followed by analysis of learning ability by the Morris water maze test, expression of miR-134, Bcl-2 and Bax by Real time PCR, BDNF protein level by Western blot, IL-6 secretion by ELISA as well as pathological changes of hippocampal nerve region by HE staining. In VD model group, the learning and cognitive ability of the rats was significantly decreased and miR- 134 and IL-6 was significantly upregulated along with downregulated Bcl-2 and BDNF and upregulated Bax expression compared to sham group (P <0.05). Humanin-S14G significantly improved the learning and cognitive ability of VD model rats, decreased miR-134 and IL-6 level, increased Bcl-2 and BDNF expression, as well as inhibited Bax expression (P <0.05) and nerve damage was significantly improved. Humanin-S14G regulates miR-134 expression in the brain tissue of VD rats, promote the expression of BDNF, regulate cell apoptosis, inhibit inflammation, improve the learning function of vascular dementia, and delay the occurrence and development of vascular dementia.

scholarly journals Synergistic Effects of Mesenchymal Stem Cell Transplantation and Repetitive Transcranial Magnetic Stimulation on Promoting Autophagy and Synaptic Plasticity in Vascular Dementia

2018 ◽  
Vol 74 (9) ◽  
pp. 1341-1350 ◽  
Author(s):  
Fei Wang ◽  
Chi Zhang ◽  
Siyuan Hou ◽  
Xin Geng
Keyword(s):  
Transcranial Magnetic Stimulation ◽  
Vascular Dementia ◽  
Magnetic Stimulation ◽  
Repetitive Transcranial Magnetic Stimulation ◽  
Synergistic Effects ◽  
Morris Water Maze Test ◽  
Control Group ◽  
Sham Operation ◽  
Therapeutic Effects ◽  
Mesenchymal Stem Cell Transplantation

Abstract Repetitive transcranial magnetic stimulation (rTMS) and mesenchymal stem cells (MSCs) transplantation both showed therapeutic effects on cognition impairment in vascular dementia (VD) model rats. However, whether these two therapies have synergistic effects and the molecular mechanisms remain unclear. In our present study, rats were randomly divided into six groups: control group, sham operation group, VD group, MSC group, rTMS group, and MSC+rTMS group. The VD model rats were prepared using a modified 2VO method. rTMS treatment was implemented at a frequency of 5 Hz, the stimulation intensity for 0.5 Tesla, 20 strings every day with 10 pulses per string and six treatment courses. The results of the Morris water maze test showed that the learning and memory abilities of the MSC group, rTMS group, and MSC+rTMS group were better than that of the VD group, and the MSC+rTMS group showed the most significant effect. The protein expression levels of brain-derived neurotrophic factor, NR1, LC3-II, and Beclin-1 were the highest and p62 protein was the lowest in the MSC+rTMS group. Our findings demonstrated that rTMS could further enhance the effect of MSC transplantation on VD rats and provided an important basis for the combined application of MSC transplantation and rTMS to treat VD or other neurological diseases.

scholarly journals Influence of malignant growth and chronic neurogenic pain on neurosteroid levels in rat brain

2020 ◽  
Vol 66 (2) ◽  
pp. 151-155
Author(s):  
E.M. Frantsiyants ◽  
V.A. Bandovkina ◽  
I.V. Kaplieva ◽  
N.D. Cheryarina ◽  
E.I. Surikova ◽  
...  
Keyword(s):  
White Matter ◽  
Free Testosterone ◽  
Male Rats ◽  
Sex Steroid ◽  
Malignant Growth ◽  
Control Groups ◽  
Neurogenic Pain ◽  
Brain White Matter ◽  
Comparison Groups ◽  
The Brain

The aim of the study was to determine the level of sex steroid hormones in white matter of the brain of rats with tumors combined with chronic neurogenic pain (CNP), which was modeled by bilateral sciatic nerve ligation. The study included albino male rats (n=74). In the main group, M1 sarcoma was transplanted subcutaneously (n=11) or into the subclavian vein (n=11) 45 days after CNP modeling. Two comparison groups (n=13 each) included sham operated animals (without CNP) with M1 sarcoma transplanted subcutaneously and intravenously. Control groups included animals with CNP and sham operated animals. Rats were euthanized on day 21 of the carcinogenesis. Levels of total and free testosterone (T), estrone (E1), estradiol (E2), estriol (E3) and progesterone (P4) in the brain white matter were measured using ELISA kits (“Cusabio”, China). CNP caused a decrease in the total and free T by 1.5 times (p

Abstract T P410: Angiopoietin-1 Mimetic Peptide Treatment Promotes White Matter Remodeling And Improves Cognitive Function In Rats With Vascular Dementia

Stroke ◽  
2015 ◽  
Vol 46 (suppl_1) ◽  
Author(s):  
Poornima Venkat ◽  
Michael Chopp ◽  
Alex Zacharek ◽  
Ruizhuo Ning ◽  
Paul Van Slyke ◽  
...  
Keyword(s):  
Cognitive Function ◽  
White Matter ◽  
Protein Expression ◽  
Cognitive Decline ◽  
Vascular Dementia ◽  
Therapeutic Effects ◽  
Synaptic Protein ◽  
Spine Density ◽  
Mimetic Peptide ◽  
Angiopoietin 1

Background and Purpose: Vascular Dementia (VaD) affects cognitive and memory function. Clinically, a series of minor or silent strokes induce subcortical lesions and may lead to VaD. In this study, we developed a multiple microinfarct-based mild VaD model in retired breeder rats and tested the therapeutic effects of an Angiopoietin-1 mimetic peptide, Vasculotide (VT) on cognitive decline and white matter (WM) damage. Methods: Male retired breeder rats were subjected to a multiple microinfarct model (500 70-100 μm cholesterol crystals injected into the internal carotid artery) and treated with 1) PBS 2) VT (3 μg/Kg, i.p. injection) starting at 1 day for 14 days (n=6/group). Neurological and cognitive deficits were evaluated 2 and 6 weeks later. Rats were sacrificed on 7th week. Results: The multiple microinfarct model induced cognitive decline in retired breeder rats starting at 2 weeks which persisted to 6 weeks after surgery. Significant (p<0.05) loss in short term memory was observed using the Novel Object Recognition Task and memory loss was evident from the Odor Test. Anxiety-like behavior was observed during Open Field evaluation. Compared to non surgery rats, VaD significantly decreased neurite branching and spine density measured by Golgi staining; induced significant WM damage identified by decreased axon and myelin density, decreased oligodendrocyte progenitor cells and oligodendrocyte number; and decreased synaptic protein expression in the corpus callosum and striatum. VaD also significantly increased RAGE (Receptor for Advanced Glycation Endproducts) expression in the brain. Treatment of VaD with VT significantly (p<0.05) improved cognitive function and memory, decreased anxiety, significantly attenuated WM damage, increased neurite branching and spine density and synaptic protein expression as well as decreased RAGE expression compared to VaD control rats (p<0.05). Conclusion: Multiple microinfarcts can induce significant WM damage and cause decline in cognition and memory. VT treatment promotes WM remodeling, synaptic plasticity and anti-inflammation which in concert may contribute to the improvement in cognition and memory.

scholarly journals Potential Therapeutic Effects of New Ruthenium (III) Complex with Quercetin: Characterization, Structure, Gene Regulation, and Antitumor and Anti-Inflammatory Studies (RuIII/Q Novel Complex Is a Potent Immunoprotective Agent)

Crystals ◽  
2021 ◽  
Vol 11 (4) ◽  
pp. 367
Author(s):  
Moamen S. Refat ◽  
Reham Z. Hamza ◽  
Abdel Majid A. Adam ◽  
Hosam A. Saad ◽  
Adil A. Gobouri ◽  
...  
Keyword(s):  
Reproductive Toxicity ◽  
Average Diameter ◽  
Testicular Tissue ◽  
Male Rats ◽  
Flavonoid Compound ◽  
Therapeutic Effects ◽  
Ultrastructural Studies ◽  
Ameliorative Effect ◽  
Anti Inflammatory ◽  
The Brain

The aim of this study was to evaluate the antioxidant and anti-inflammatory effects of the new [Ru(Q)(Cl)2(H2O)2] complex (RuIII/Q). A new vital complex containing quercetin flavonoid compound (Q) with ruthenium (III) ions was synthesized. The molar conductivity of the RuIII/Q complex was measured in dimethylsulfoxide (DMSO) with value 12 (Ω−1 mol−1 cm−1, indicating their non-electrolytic nature. Infrared (FTIR) spectroscopic investigation of the RuIII/Q complex indicated that Q is coordinated as a bidentate with Ru metal ions through the oxygen of carbonyl C(4)=O group and oxygen of phenolic C(3)−O group based on the wavenumber shifts at 1654 and 1335 cm−1 respectively. The electronic (UV−Vis) spectra and the magnetic susceptibility value (1.85 B.M.) revealed that the Ru(III) complex has an octahedral geometry. The average diameter of the RuIII/Q nanoparticles was approximately 7–15 nm according to the transmission electron microscopy. The thermogravimetric study (TG/DTG) indicates that the RuIII/Q compound is quite stable until 300 °C. To assess biological activity, 60 male rats were allocated to six groups, namely control, DG (D-galactose), Q, RuIII/Q, DG plus Q, and DG plus RuIII/Q. Antioxidant enzymes (SOD, CAT, GPx, and GRx), markers of lipid peroxidation (such as MDA), expression of genes (namely Nrf2, Cu-ZnSOD, CAT, GPx, cyto c, P53, Bax, BCl2, caspase-3, and caspase-9 in testicular tissue), glutamate, 4-hydroxynonenal (HNE), GSH, HCY, amyloid beta, and GABA levels were evaluated in brain tissues. Cytokines, such as IL-6 and TNF-α, histological and ultrastructural studies were estimated in both the brain and testicular tissues, while the comet assay was performed in the brain tissue. RuIII/Q administration either alone or combined with DG reduced oxidative injury to normal levels and decreased apoptotic activities. Thus, RuIII/Q inhibited injury in both the testis and brain and reduced oxidative stress in male rats. The (RuIII/Q) complex has a potent ameliorative effect against aging neurotoxicity, reproductive toxicity, and antihepatic cancer activity induced by D-galactose (DG).

Chronic immobilization stress induces anxiety-related behaviors and affects brain essential minerals in male rats

2020 ◽  
pp. 1-8
Author(s):  
Zafer Sahin ◽  
Alpaslan Ozkurkculer ◽  
Omer Faruk Kalkan ◽  
Ahmet Ozkaya ◽  
Aynur Koc ◽  
...  
Keyword(s):  
Immobilization Stress ◽  
Central Area ◽  
Essential Elements ◽  
Male Rats ◽  
Control Group ◽  
Male Wistar Rats ◽  
Swimming Test ◽  
The Brain ◽  
Center Area ◽  
Chronic Immobilization Stress

Abstract. Alterations of essential elements in the brain are associated with the pathophysiology of many neuropsychiatric disorders. It is known that chronic/overwhelming stress may cause some anxiety and/or depression. We aimed to investigate the effects of two different chronic immobilization stress protocols on anxiety-related behaviors and brain minerals. Adult male Wistar rats were divided into 3 groups as follows ( n = 10/group): control, immobilization stress-1 (45 minutes daily for 7-day) and immobilization stress-2 (45 minutes twice a day for 7-day). Stress-related behaviors were evaluated by open field test and forced swimming test. In the immobilization stress-1 and immobilization stress-2 groups, percentage of time spent in the central area (6.38 ± 0.41% and 6.28 ± 1.03% respectively, p < 0.05) and rearing frequency (2.75 ± 0.41 and 3.85 ± 0.46, p < 0.01 and p < 0.05, respectively) were lower, latency to center area (49.11 ± 5.87 s and 44.92 ± 8.04 s, p < 0.01 and p < 0.01, respectively), were higher than the control group (8.65 ± 0.49%, 5.37 ± 0.44 and 15.3 ± 3.32 s, respectively). In the immobilization stress-1 group, zinc (12.65 ± 0.1 ppm, p < 0.001), magnesium (170.4 ± 1.7 ppm, p < 0.005) and phosphate (2.76 ± 0.1 ppm, p < 0.05) levels were lower than the control group (13.87 ± 0.16 ppm, 179.31 ± 1.87 ppm and 3.11 ± 0.06 ppm, respectively). In the immobilization stress-2 group, magnesium (171.56 ± 1.87 ppm, p < 0.05), phosphate (2.44 ± 0.07 ppm, p < 0.001) levels were lower, and manganese (373.68 ± 5.76 ppb, p < 0.001) and copper (2.79 ± 0.15 ppm, p < 0.05) levels were higher than the control group (179.31 ± 1.87 ppm, 3.11 ± 0.06 ppm, 327.25 ± 8.35 ppb and 2.45 ± 0.05 ppm, respectively). Our results indicated that 7-day chronic immobilization stress increased anxiety-related behaviors in both stress groups. Zinc, magnesium, phosphate, copper and manganese levels were affected in the brain.

The Acute Effect of Alcohol on Various Memory Processes

2010 ◽  
Vol 24 (4) ◽  
pp. 249-252 ◽  
Author(s):  
Márk Molnár ◽  
Roland Boha ◽  
Balázs Czigler ◽  
Zsófia Anna Gaál
Keyword(s):  
Low Dose ◽  
Short Term Memory ◽  
Acute Effect ◽  
Long Term Memory ◽  
Term Memory ◽  
Memory Processes ◽  
Different Types ◽  
The Brain ◽  
Legal Consequences

This review surveys relevant and recent data of the pertinent literature regarding the acute effect of alcohol on various kinds of memory processes with special emphasis on working memory. The characteristics of different types of long-term memory (LTM) and short-term memory (STM) processes are summarized with an attempt to relate these to various structures in the brain. LTM is typically impaired by chronic alcohol intake but according to some data a single dose of ethanol may have long lasting effects if administered at a critically important age. The most commonly seen deleterious acute effect of alcohol to STM appears following large doses of ethanol in conditions of “binge drinking” causing the “blackout” phenomenon. However, with the application of various techniques and well-structured behavioral paradigms it is possible to detect, albeit occasionally, subtle changes of cognitive processes even as a result of a low dose of alcohol. These data may be important for the consideration of legal consequences of low-dose ethanol intake in conditions such as driving, etc.

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