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.

Zhuyu Annao decoction promotes angiogenesis in mice with cerebral hemorrhage by inhibiting the activity of PHD3

2021 ◽  
pp. 096032712110085
Author(s):  
L Wu ◽  
Y Hu ◽  
L Jiang ◽  
N Liang ◽  
P Liu ◽  
...  
Keyword(s):  
Oxidative Stress ◽  
Signaling Pathway ◽  
Morris Water Maze ◽  
Cerebral Hemorrhage ◽  
Water Maze ◽  
Luciferase Reporter ◽  
Morris Water Maze Test ◽  
Therapeutic Effects ◽  
Vascular Endothelial ◽  
Behavioral Experiments

Some traditional Chinese decoctions, such as Zhuyu Annao, exert favorable therapeutic effects on acute cerebral hemorrhage, hemorrhagic stroke, and other neurological diseases, but the underlying mechanism remains unclear. This study aimed to determine whether Zhuyu Annao decoction (ZYAND) protects the injured brain by promoting angiogenesis following intracerebral hemorrhage (ICH) and elucidate its specific mechanism. The effect of ZYAND on the nervous system of mice after ICH was explored through behavioral experiments, such as the Morris water maze and Rotarod tests, and its effects on oxidative stress were explored by detecting several oxidative stress markers, including malondialdehyde, nitric oxide, glutathione peroxidase, and superoxide dismutase. Real-time quantitative RT-PCR and WB were used to detect the effects of ZYAND on the levels of prolyl hydroxylase domain 3 (PHD3), hypoxia-inducible factor-1α (HIF-1α), and vascular endothelial growth factor (VEGF) in the brain tissues of mice. The effect of ZYAND on the NF-κB signaling pathway was detected using a luciferase reporter gene. A human umbilical cord vascular endothelial cell angiogenesis experiment was performed to determine whether ZYAND promotes angiogenesis. The Morris water maze test and other behavioral experiments verified that ZYAND improved the neurobehavior of mice after ICH. ZYAND activated the PHD3/HIF-1α signaling pathway, inhibiting the oxidative damage caused by ICH. In angiogenesis experiments, it was found that ZYAND promoted VEGF-induced angiogenesis by upregulating the expression of HIF-1α, and NF-κB signaling regulated the expression of HIF-1α by inhibiting PHD3. ZYAND exerts a reparative effect on brain tissue damaged after ICH through the NF-κB/ PHD3/HIF-1α/VEGF signaling axis.

scholarly journals Predicting outcome of Morris water maze test in vascular dementia mouse model with deep learning

PLoS ONE ◽  
2018 ◽  
Vol 13 (2) ◽  
pp. e0191708 ◽  
Author(s):  
Akinori Higaki ◽  
Masaki Mogi ◽  
Jun Iwanami ◽  
Li-Juan Min ◽  
Hui-Yu Bai ◽  
...  
Keyword(s):  
Deep Learning ◽  
Mouse Model ◽  
Vascular Dementia ◽  
Morris Water Maze ◽  
Water Maze ◽  
Morris Water Maze Test ◽  
Maze Test ◽  
Predicting Outcome

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 Inhibition of Rho Kinase by Fasudil Ameliorates Cognition Impairment in APP/PS1 Transgenic Mice via Modulation of Gut Microbiota and Metabolites

2021 ◽  
Author(s):  
Yuqing Yan ◽  
Ye Gao ◽  
Qingli Fang ◽  
Nianping Zhang ◽  
Gajendra Kumar ◽  
...  
Keyword(s):  
Gut Microbiota ◽  
Morris Water Maze ◽  
Water Maze ◽  
Kinase Inhibitor ◽  
Rho Kinase ◽  
Morris Water Maze Test ◽  
Therapeutic Effects ◽  
Model Of Alzheimer’S Disease ◽  
Potential Biomarker ◽  
Potential Biomarkers

Abstract Background: Fasudil, a Rho kinase inhibitor, exerts therapeutic effects in the mouse model of Alzheimer’s disease (AD), a chronic neurodegenerative disease with progressive loss of memory. However, the mechanisms remain unclear. In addition, the gut microbiota and its metabolites have been implicated in AD. Methods: Here, we examined the effect of fasudil on learning and memory using the Morris water-maze (MWM) test in APPswe/PSEN1dE9 transgenic (APP/PS1) mice (8 months old) treated (i.p.) with fasudil (25 mg/kg/day; ADF) or saline (ADNS) and in age- and gender-matched wild-type (WT) mice. Fecal metagenomics and metabolites were analyzed to identify novel biomarkers of AD and to elucidate the mechanisms whereby fasudil produced beneficial effects in AD mice. Results: Morris water maze test showed significant improvement of spatial memory in APP/PS1 mice treated with fasudil as compared to ADNS. The metagenomic analysis revealed the abundance of the dominant phyla in all the three groups, including Bacteroidetes (23.7% - 44%) and Firmicutes (6.4% - 26.6%), and the increased relative abundance ratio of Firmicutes/Bacteroidetes in ADNS (59.1%) compared to WT (31.7%). In contrast, the Firmicutes/Bacteroidetes ratio was decreased to the WT level in ADF (32.8%). Lefse analysis results of metagenomics showed s_Prevotella_sp_CAG873 as an ADF potential biomarker, while s_Helicobacter_typhlonius and s_Helicobacter_sp_MIT_03-1616 as ADNS potential biomarkers. Metabolite analysis revealed the increment of various metabolites, including glutamate, hypoxanthine, thymine, hexanoyl-CoA, and leukotriene, were relative to ADNS or ADF microbiota potential biomarkers and mainly involved in the metabolism of nucleotide, lipids, sugars, and the inflammatory pathway. Conclusions: Memory deficit in APP/PS1 mice was correlated with the gut microbiome and metabolite status. Fasudil reversed the abnormal gut microbiota and subsequently regulated the related metabolisms to normal in the AD mice. It is believed that fasudil can be a novel strategy for the treatment of AD via remodeling of the gut microbiota and metabolites. The novel results also provide valuable references for the use of gut microbiota and metabolites as diagnostic biomarkers and/or therapeutic targets in clinical studies of AD.

scholarly journals Luteolin attenuates cognitive dysfunction induced by chronic cerebral hypoperfusion through the modulation of the PI3K/Akt pathway in rats

2021 ◽  
Vol 0 (0) ◽  
Author(s):  
Haitao He ◽  
Xi Chen
Keyword(s):  
Cerebral Cortex ◽  
Object Recognition ◽  
Cognitive Dysfunction ◽  
Morris Water Maze ◽  
Water Maze ◽  
Sham Group ◽  
Cerebral Hypoperfusion ◽  
Morris Water Maze Test ◽  
Model Group ◽  
Group I

Abstract Introduction In our study, we evaluated the beneficial effect of luteolin in the treatment of cognitive dysfunction in rat models induced by cerebral hypoperfusion by two-vessel occlusion (2-VO). Material and Methods Seventy-five male Sprague Dawley rats were subjected to 2-VO surgery, in all but 15 (the sham group, group I) the ligation being permanent to impair cognitive abilities. The sham group rats received saline instead of a drug; 15 2-VO rats were not injected at all (the model group, group II); 15 2-VO rats were administered luteolin at 50 mg/kg b.w. (the lut 50 group, group III); to a further 15 luteolin was given at 100 mg/kg b.w. (the lut 100 group, group IV); and the final 15 received nimodipine at 16 mg/kg b.w. as positive controls (the nimodipine group, group V). Object recognition and Morris water maze tests were performed to investigate memory ability. A Western blot test was also conducted to assess expression of phosphatidylinositol 3-kinase (PI3K), its downstream target protein kinase B (Akt), and the phosphorylated form (P-Akt) in cerebral cortex and hippocampus tissue samples. Results Significant variations in the discrimination index in the object recognition test, the escape latencies in the Morris water maze test, and expression levels of PI3K-p110α and PI3K-p85 were observed three months after 2-VO surgery in both lut groups, with a significant change in the nimodipine group compared to the model group. P-Akt and Akt were expressed significantly higher in both lut groups and the nimodipine group than in the model group. Conclusion Luteolin treatment of rats cognitively dysfunctional after experimental cerebral hypo perfusion was neuroprotective by activating the PI3K/Akt signals which inhibit neuronal death in the cerebral cortex and hippocampal region.

Abstract P233: Mas Receptor Deficiency Does Not Impair Cognitive Funcion of Vascular Dementia Model in the Presence of Angiotensin II Type 2 Receptor

Hypertension ◽  
2017 ◽  
Vol 70 (suppl_1) ◽  
Author(s):  
Akinori Higaki ◽  
Masaki Mogi ◽  
Jun Iwanami ◽  
Li-Juan Min ◽  
Harumi Kan-no ◽  
...  
Keyword(s):  
Vascular Dementia ◽  
Morris Water Maze ◽  
Knockout Mice ◽  
Water Maze ◽  
Morris Water Maze Test ◽  
Mas Receptor ◽  
Maze Test ◽  
Y Maze ◽  
Significant Difference

Objective: Angiotensin (Ang) converting enzyme (ACE) 2/ Ang-(1-7)/Mas receptor axis has been considered as protective arm in the renin-angiotensin system and Ang-(1-7) is thought to interact with Ang II type 2 (AT 2 ) receptor according. Mas receptor is expressed highly in hippocampus and blood vessels in brain, but its actual function is still unclear. Thus, we examined the possible roles of Mas receptor in relation to the vascular cognitive impairment focusing on the interaction with AT 2 receptor. Design and Methods: Male 10-week-old C57BL6 mice (wild-type, WT), Mas1 receptor knockout mice (MasKO) and AT 2 /Mas1 receptor double knockout mice (DKO) were subjected to bilateral carotid artery stenosis (BCAS) surgery. After six weeks from the treatment, we evaluated their cognitive function with Y-maze test and the Morris water maze test. Results: The cerebral blood flow (CBF) in each BCAS group was significantly reduced compared to its sham-operated counterparts (WT; 31.5±0.6 vs 28.0±0.8, MasKO; 31.7±0.8 vs 27.7±0.8, DKO; 33.0±0.5 vs 29.1±0.7). The alternation behavior (%) was significantly reduced in WT mice with BCAS compared to sham mice (69.6±3.5 vs 57.9±2.1), but there was no significant difference in MasKO and DKO mice (MasKO; 64.1±2.5 vs 63.1±2.5, DKO; 67.6±2.1 vs 61.1±4.0) in Y maze test. In the Morris water maze test, the mean arrival time at platform at day 5 (sec) was significantly higher in WT-BCAS mice than WT-sham mice (Sham; 20.9±4.6 vs BCAS; 47.3±6.5). In contrast to the results in WT, there was no significant difference in MasKO mice (Sham; 32.8±8.5 vs BCAS; 34.5±7.3). DKO-sham mice showed significantly lower spatial learning ability compared with WT-sham mice (DKO; 77.4±11.9 vs WT; 20.9±4.6). The total cell count in dentate gyrus area was significantly lower in WT-BCAS compared to WT-sham (sham; 255.7±7.0 vs BCAS; 209.4±5.4), but there was no significant change in MasKO mice(sham; 256.5±2.5 vs BCAS; 233.2±16.4). We could not see significant difference in the number of DCX-positive cells and the expressions of proinflammatory cytokines such as IL-6, TNF-α and MCP-1in all mouse groups. Conclusion: Mas receptor deficiency seems to be beneficial in vascular dementia on condition that AT 2 receptor exists.

scholarly journals Effects of oral ingestion of hyoscyamine from Daturastramonium seeds on the hippocampus in adult Wistar rats (Rattusnorvegicus)

2021 ◽  
Vol 13 (2) ◽  
pp. 36-46
Author(s):  
A. T. Idris ◽  
A.M. Sunday ◽  
A.I. Ibrahim ◽  
O.N. James ◽  
A.K. Musa ◽  
...  
Keyword(s):  
Object Recognition ◽  
Morris Water Maze ◽  
Repeated Measures ◽  
Water Maze ◽  
Wistar Rats ◽  
Morris Water Maze Test ◽  
Control Group ◽  
Novel Object Recognition ◽  
Oral Ingestion ◽  
Novel Object

The study aimed to evaluate the effects of oral ingestion of hyoscyamine fraction of Daturastramonium seeds on the hippocampus in adult Wistar rats. Fresh seeds of D. stramonium were procured and fractionated using high-performance liquid chromatography (HPLC). Twenty-four healthy adult Wistar rats weighed 230±0.50 grams, were procured and divided equally into four groups for the experiment. The group one received an equivalent bodyweight of normal saline, while three other groups received 200, 400 and 800 mg/kgbwt of hyoscyamine fraction of D. stramonium respectively for three weeks. At the end of the experiment, the animals were subjected to memory test using Morris water maze (MWM) and Novel object recognition test (NORT) test paradigms. The data obtained were expressed as mean ± SEM and repeated measures ANOVA with Fisher’s multiple comparisons post-hoc tests were used to obtain mean differences using Minitab 17 (LLC., U.K.) statistical package software. P < 0.05  was considered statistically significant. There was a statistically significant increase in the exploration time (p = 0.031) and escape latency period (p < 0.001) in the novel object recognition and Morris water maze test between the groups in the treated compared to the control group. The CA3 region of the treated group showed significant neuronal lesions, cytoplasmic vacuolations, pyknosis and necrosis. . In conclusion, exposure to hyoscyamine fraction of D.stramonium at adulthood impaired memory in Wistar rats.  

scholarly journals Hydrolase-Treated Royal Jelly Attenuates H2O2- and Glutamate-Induced SH-SY5Y Cell Damage and Promotes Cognitive Enhancement in a Rat Model of Vascular Dementia

2021 ◽  
Vol 2021 ◽  
pp. 1-11
Author(s):  
Nualpun Sirinupong ◽  
Worrapanitch Chansuwan ◽  
Pratchaya Kaewkaen
Keyword(s):  
Vascular Dementia ◽  
Morris Water Maze ◽  
Water Maze ◽  
Royal Jelly ◽  
Cell Damage ◽  
Acetylcholinesterase Inhibitor ◽  
Neuroblastoma Cells ◽  
Morris Water Maze Test ◽  
Radial Arm Maze

Vascular dementia (VaD) is the second most common type of dementia following Alzheimer’s disease, but the therapeutic efficacy is still not effective. This makes the searching for novel neuroprotective agents important. Therefore, we hypothesized that royal jelly, a well-known traditional medicine, could attenuate memory impairment and brain damage in vascular dementia. This study determined the effects of royal jelly hydrolysate (RJH) and possible mechanism of cell damage and cognitive-enhancing effect in animal study. An in vitro study assessed the effects of RJH on acetylcholinesterase inhibitor, cell viability, and cell damage in SH-SY5Y neuroblastoma cells. Then, an in vivo study examined vascular dementia by the occlusion of the right middle cerebral artery (Rt.MCAO); adult male Wistar rats had been orally given RJH at doses ranging from 10, 50, to 100 mg/kg for 14 days before and 14 days after the occlusion of Rt.MCAO to mimic the VaD condition. Rats’ spatial memory was evaluated using Morris water maze and radial arm maze every 7 days after Rt.MCAO throughout a 14-day experimental period, and then, they were sacrificed and the acetylcholinesterase (AChE) activity in the hippocampus was determined. The results showed that RJH has no cytotoxic effect with the final concentration up to 500 μg protein/ml and reduces cell death from the H2O2- and glutamate-induced cell damage in in vitro neuroblastoma cells. Importantly, RJH significantly improved memory performance in Morris water maze test and radial arm maze and decreased the level of acetyl cholinesterase activity. In conclusion, RJH is the potential neuroprotective agent and cognitive enhancer for VaD.

scholarly journals Musical Electroacupuncture May Be a Better Choice than Electroacupuncture in a Mouse Model of Alzheimer’s Disease

2016 ◽  
Vol 2016 ◽  
pp. 1-9 ◽  
Author(s):  
Jing Jiang ◽  
Gang Liu ◽  
Suhua Shi ◽  
Zhigang Li
Keyword(s):  
Alzheimer’S Disease ◽  
Alzheimer's Disease ◽  
Mouse Model ◽  
Frontal Lobe ◽  
Morris Water Maze ◽  
Water Maze ◽  
Morris Water Maze Test ◽  
Maze Test ◽  
Model Of Alzheimer’S Disease ◽  
Samp8 Mice

Objectives. To compare musical electroacupuncture and electroacupuncture in a mouse model of Alzheimer’s disease.Methods. In this study, 7.5-month-old male senescence-accelerated mouse prone 8 (SAMP8) mice were used as an Alzheimer’s disease animal model. In the normal control paradigm, 7.5-month-old male SAMR1 mice were used as the blank control group (N group). After 15 days of treatment, using Morris water maze test, micro-PET, and immunohistochemistry, the differences among the musical electroacupuncture (MEA), electroacupuncture (EA), Alzheimer’s disease (AD), and normal (N) groups were assessed.Results. The Morris water maze test, micro-PET, and immunohistochemistry revealed that MEA and EA therapies could improve spatial learning and memory ability, glucose metabolism level in the brain, and Aβamyloid content in the frontal lobe, compared with the AD group (P<0.05). Moreover, MEA therapy performed better than EA treatment in decreasing amyloid-beta levels in the frontal lobe of mice with AD.Conclusion. MEA therapy may be superior to EA in treating Alzheimer’s disease as demonstrated in SAMP8 mice.

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