Rat Model Of Vascular Dementia Research Articles

Glycyrrhizic Acid Ameliorates Cognitive Impairment in a Rat Model of Vascular Dementia Associated with Oxidative Damage and Inhibition of Voltage-Gated Sodium Channels.

Vascular dementia (VD) is the second most common cause of cognitive impairment in the elderly population. Our study aims to investigate the neuroprotective effects of glycyrrhizic acid (GA), a major active constituent of Glycyrrhiza glabra root, in a VD rat model induced by permanent occlusion of the bilateral common carotid arteries. Spatial cognitive function was examined by the Morris water maze test and synaptic plasticity was explored by assessing long-term potentiation. The results showed that GA (20 mg/kg for 5 days) significantly improved the performance of learning and memory of VD rats in the Morris water maze test and attenuated induction of long-term potentiation. Histopathological studies showed that GA significantly attenuated cell damage in VD rats. Malondialdehyde levels and superoxide dismutase activity were analyzed in the hippocampus and cortex to investigate anti-oxidant status. The results showed that GA decreased the level of lipid peroxidation and increased the activity of superoxide dismutase in VD rats. Lastly, whole-cell patch-clamp analysis was used to examine the effect of GA on voltage-gated sodium channels (VGSCs) in hippocampal CA1 pyramidal neurons. GA (10, 20 and 50 μM) inhibited the current amplitude of the VGSCs. These results suggest that the neuroprotective e.ects of GA in VD rats relate to the reduction of oxidative stress and inhibition of VGSCs. Our study provides experimental evidence for the application of GA in the treatment of cognitive deficits induced by Alzheimer's disease, stroke, or traumatic brain injury.

Effects of a Cardiotonic Medicine, Danshen Pills, on Cognitive Ability and Expression of PSD-95 in a Vascular Dementia Rat Model

A widely used Chinese cardiotonic proprietary medicine, compound Danshen dripping pills (CDDP, Fufang Danshen Diwan) has also begun to be used for treatment of vascular dementia (VaD). We tried to explore the mechanism of CDDP action in this case. A VaD experimental model was built in rats by bilateral ligation of the common carotid arteries. The cognitive ability of experimental animals was evaluated in the Morris water maze test. Synaptic ultrastructural changes in the hippocampus were detected by transmission electron microscopy; expression of PSD-95 mRNA in the hippocampus was examined using hybridization in situ. The latter index (mRNA expression) in the VaD group was significantly lower than those in the CDDP and sham-operated groups (P < 0.05). CDDP treatment considerably improved disturbed ultrastructural synaptic characteristics in the hippocampus of VaD rats. The mean escape latency in the Morris water maze test was significantly shorter in CDDP-treated VaD rats, compared with that those of the VaD group (P < 0.05). In the CDDP group compared to the VaD one, escape strategies improved from edge and random searches to more linear swim pathway (P < 0.05). Thus, decreasing expression of PSD-95 plays an important role in the pathogenesis of VaD. CDDP treatment improves the learning and memory ability of VaD rats by improving neural synaptic ultrastructural characteristics and increasing expression of PSD-95 mRNA in the hippocampus.

Protective Effect of Low-Intensity Pulsed Ultrasound on Memory Impairment and Brain Damage in a Rat Model of Vascular Dementia.

Purpose To investigate the neuroprotective effects of low-intensity pulsed (LIP) ultrasound on memory impairment and central nervous system injury in a rat model of vascular dementia. Materials and Methods All animal experiments were approved by the animal care and use committee and adhered to experimental animal care guidelines. A 1.0-MHz focused ultrasound transducer was used to stimulate the brain noninvasively with 50-msec bursts at a 5% duty cycle, repetition frequency of 1 Hz, and spatial peak temporal average intensity of 528 mW/cm2. LIP ultrasound treatment was performed daily with triple sonications in each hemisphere. The duration of each sonicaton was 5 minutes, with a 5-minute interval between each sonication. Permanent bilateral common carotid artery occlusion (BCCAO) was used as a model of vascular dementia. After 2 weeks of LIP ultrasound, neuroprotective effects of LIP ultrasound were evaluated with behavioral analysis, including the passive avoidance task and elevated plus maze. Myelin content was detected with carbon 11 (11C) Pittsburgh compound B (PIB). Brain sections were stained with hematoxylin-eosin and Luxol fast blue. Two-way analysis of variance and Student t test were used for statistical analyses, with a significance level of .05. Results Protein expressions of brain-derived neurotrophic factor (BDNF) in the BCCAO rats treated with LIP ultrasound were significantly higher than those in BCCAO rats (1.1 ± 0.0 vs 0.8 ± 0.1, P < .05). BCCAO rats exhibited neuronal damage and demyelination. Compared with the BCCAO group, 11C PIB accumulation in the BCCAO rats treated with LIP ultrasound was significantly (P < .05) increased by 67.4% and 203.0% in the hippocampus and corpus callosum, respectively. Hematoxylin-eosin staining showed that neuronal injury in the hippocampal cornu ammonis 1 region was alleviated with LIP ultrasound. Luxol fast blue staining of the corpus callosum was significantly greater in the BCCAO rats treated with LIP ultrasound than in the untreated BCCAO rats (mean, 94.5% ± 2.3 [standard error] vs 86.6% ± 1.0; P < .05). Moreover, LIP ultrasound stimulation significantly improved learning and memory abilities and morphology in rats with vascular dementia compared with rats with untreated vascular dementia (P < .05). Conclusion These results suggest LIP ultrasound stimulation protects against brain injury in the hippocampus and corpus callosum in rats with vascular dementia. The beneficial effect of LIP ultrasound may be partly induced by upregulation of protein expression of BDNF. © RSNA, 2016.

Tanshinol suppresses inflammatory factors in a rat model of vascular dementia and protects LPS-treated neurons via the MST1-FOXO3 signaling pathway

Neuroinflammation plays an important role in vascular dementia(VD). Our previous work showed that mammalian Ste20-like kinase 1 (MST1) and the gene for a downstream transcription factor, FOXO3, play major roles in lipopolysaccharide (LPS)-induced apoptosis in hippocampal neurons. The neurotoxic effects of LPS are derived from its ability to cause an inflammatory response. We also previously showed that Tanshinol (TSL) provides neuro-protection in a rat model of VD. The present study further explores the effects of TSL on the neuroinflammatory aspects of VD and investigates whether TSL affects the MST1-FOXO3signaling pathway. VD was induced in rats using transient bilateral coronary artery occlusion. Interleukin(IL)-1β, IL-6, and tumor necrosis factor (TNF)-α levels were measured using enzyme-linked immunoabsorbent assay kits. Cell apoptosis was assessed by Hoechst 33342 staining. Protein and mRNA levels were evaluated by western blotting and quantitative polymerase chain reaction, respectively. TSL improved working memory and significantly inhibited plasma and hippocampal protein levels of IL-1β, IL-6, and TNF-α in a rat model of VD. LPS induced apoptosis in hippocampal neurons and increasedMST1 and p-FOXO3 protein expression, whereas MST1 siRNA transfection almost completely reversed LPS-induced neuronal apoptosis, indicating that LPS-induced cytotoxicity in hippocampal neurons is associated with MST1. TSL protected against LPS-induced cell apoptosis and suppressed IL-1β, IL-6, and TNF-α mRNA and protein expression as well as MST1 and p-FOXO3 protein expression in neurons. The present study provided novel mechanisms by which TSL exerts its neuroprotective activity and indicates that TSL may be a potential neuro-protective agent in VD.

GABAB receptors in the hippocampal dentate gyrus are involved in spatial learning and memory impairment in a rat model of vascular dementia.

The roles of γ-aminobutyric acid (GABA) and GABAB receptors of the hippocampal dentate gyrus (DG) in spatial learning and memory impairment were investigated in a rat model of vascular dementia (VaD) established by permanent bilateral carotid occlusion. The extracellular concentration of GABA in the DG was determined by in vivo microdialysis and HPLC, and spatial learning and memory were assessed by the Morris water maze (MWM) test. Next, the possible involvement of GABAB receptors in spatial learning and memory impairments of VaD rats was examined by microinjection of its antagonist into the DG region. In VaD group rats, the extracellular concentration of GABA in the DG was significantly increased, and during MWM test, the escape latency was increased in place navigation trial and the percentage of time spent in target quadrant and the number of platform crossings were decreased in spatial probe trial, compared with the sham group. In sham-operated rats, the extracellular concentrations of glutamate (Glu) and glycine (Gly) in the DG were significantly increased during place navigation trial of MWM test, and these responses were inhibited in VaD rats. Saclofen (an antagonist of GABAB receptor) significantly attenuated the spatial learning and memory impairment in VaD rats, and partly reversed the inhibitory effects of VaD in responses of Glu and Gly in the DG during MWM test. Our results suggest that GABA and GABAB receptors in the hippocampal DG are involved in spatial learning and memory impairment in VaD rats, in part by attenuating the responses of Glu and Gly during spatial learning.

RETRACTED: Neuroprotective and memory enhancing effects of auraptene in a rat model of vascular dementia: Experimental study and histopathological evaluation

Vascular dementia and Alzheimer disease are most common type of dementia. These diseases have been associated with cognitive decline and affected personal behavioral activities. Moreover, the pattern of cerebral blood flow in mild cognitive disorder has appeared as a predictive indication for the development into Alzheimer's disease. Permanent, bilateral occlusion of the common carotid arteries (2VO) is a standard animal model to study vascular dementia and chronic cerebral hypoperfusion. In present study neuroprotective and memory enhancing effects of auraptene (AUR), a citrus coumarin, were studied in 2VO rats. Different doses (25, 8 & 4mg/kg) of AUR were administered orally. The spatial memory performance was tested with Morris water maze after 2VO induction. Biochemical experiments and histopathological evaluations were also applied to investigate the neuroprotective effect of AUR in brain tissue. In comparison with 2VO group, AUR could significantly decrease the scape latency time in treated rats. Also AUR increased the percentage of time spent and traveled pathway in target quadrant on final trial test day. All behavioral results were confirmed by biochemical and histopathological data. Biochemical data indicated that AUR could decrease malondialdehyde (MDA), as lipid peroxidation indicator, and increase glutathione (GSH) content in cortex and hippocampus tissues. Histopathological data showed that AUR could protect cerebrocortical and hippocampus neurons against ischemia. This study demonstrated the memory enhancing effect and neuroprotective activity of AUR after induction of brain ischemia in a rat model of vascular dementia.

Hydroxysafflor yellow A increases BDNF and NMDARs in the hippocampus in a vascular dementia rat model

Hydroxysafflor yellow A (HSYA) is a drug that exerts angiogenesis regulatory and neuroprotective effects and has become an effective therapy for brain and heart ischemic disorders. There is no definite evidence supporting a therapeutic effect of HSYA in vascular dementia (VaD). We used HSYA in a rat model of chronic cerebral ischemia to determine its potential therapeutic effects in VaD. The Morris water maze (MWM) was used to evaluate spatial cognitive function, and long-term potentiation (LTP) was tested as a marker of synaptic plasticity. The expression levels of brain-derived neurotrophic factor (BDNF) and two subunits of N-methyl-d-aspartate receptor (NMDAR; GluN2A and GluN2B) in the hippocampus were measured via western blotting. The MWM results showed that the experimental VaD group had longer escape latencies than the sham group, whereas the HSYA group had a decreased escape latency compared with the VaD group (P<0.05). The LTP at CA3-CA1 synapses in the hippocampus was also enhanced in the HSYA compared with the VaD group (P<0.05). The western blotting results revealed lower hippocampal BDNF and GluN2B expression in the VaD group compared with the sham group and significantly higher hippocampal expression in the HSYA group compared with the VaD group. No significant change in GluN2A expression was detected. The results indicate that HSYA may enhance the endogenous expression of BDNF and GluN2B, which are associated with the synaptic plasticity of the hippocampus, and may improve spatial learning and memory abilities in a rat model of VaD.

Hyperbaric oxygen therapy can improve the learning capacity and memory in vascular dementia

Objective To explore the influence of hyperbaric oxygen therapy (HBOT) on the learning and memory ability using a rat model of vascular dementia (VD). Methods Sixty Sprague-Dawley rats were selected and divided into a normal group, a sham operation group, a VD group and an HBOT group, each of 15 rats using a random number table. The improved four-vessel method was used to establish a VD model in all except the rats in the normal group, but for the sham operation group, the vertebral artery was not subjected to firing and the arteria carotis communis was not clipped. The HBOT group was then given HBOT for 7 days. The Morris water maze test was used to evaluate their learning and memory ability of all 4 groups. Results Compared to the normal group, the mean escape latency of the sham operation group, the VD group and the HBOT group was significantly longer in each case (P<0.05). Their platform quadrant crossing times were also significantly less, and their quadrant swimming distance as a proportion of their total swimming distance was significantly smaller (P<0.05). Compared with the sham operation group, the mean escape latency of the VD and HBOT groups was significantly longer (P<0.05), the times of crossing platform quadrant were less and their quadrant swimming distance was a smaller proportion of their total swimming distance. As compared with the VD group, the mean escape latency of the HBOT group was significantly shorter [(25.73±6.20) s], the average platform quadrant crossing times were significantly more [(9.51±2.25) times] and the platform quadrant swimming distance of the HBOT group was significantly longer [(494.72±208.26)], representing a significantly larger proportion of the total swimming distance [(28.71±5.32)%](P<0.05). Conclusion HBOT can effectively improve learning and memory in vascular dementia, at least in rats. Key words: Hyperbaric oxygen therapy; Vascular Dementia; Morris water maze; Learning; Memory

A rat model of vascular dementia for evaluating Chinese medicine prescriptions.

To develop a new model of vascular dementia for evaluating Chinese medicine prescriptions. Eighty-eight male Wistar rats were randomly divided into 4 groups. At d00, d42, d70, d98 (ni=20, 20, 24, 24) during fatty-feeding, rats in each group were further divided into 10 or 12 subgroups (ni=2), respectively. Lacunar stroke were replicated with the injection of thrombi which coagulated artificially from itself blood. The median lethal doses (LD50) were regressed from accumulative mortality in each geometric thrombus doses (k=0.75, 0.5, 0.85, 0.85), respectively. The degree of vascular dementia was evaluated as exploratory, learning and memorizing abilities. The median effective dose of thrombus for replicating rat model was regressed from dementia scores which were derived from the abilities. The linear correlation was regressed between the values of LD50 or effective dose (ED50) and the durations (days) of hypercholesterolemia. This model of vascular dementia was pathologically confirmed as the neural injuries from lacunar stroke in rats. The hypercholesterolemia was indicated as elevated total cholesterol, triglyeerides low-density lipoprotein cholesterol, and decreased high-density lipoprotein cholesterol. The values of LD50 with its 95% confidence intervals (CI) were 1525.0 (1361.0-1709.0), 584.3 (490.1-696.6), 168.7 (163.7-173.8), or 62.4 (59.5-65.4) mg/mL, at d00, d42, d70, and d98, respectively. There is a linear regression between the values of LD50 and the durations of hypercholesterolemia (y=-15.33x+1390.0, r=0.963, P<0.05). The values of ED50 with its 95% CI were 528.8 (340.5-821.4), 217.0 (20.84-2259.0), 96.3 (23.4-402.6), or 47.0 (43.7-50.6) mg/mL from dementia score, at d00, d42, d70, and d98, respectively. There is a linear regression between the values of ED50 and the durations of hypercholesterolemia (y=-4.992x+484.2, r=0.965, P<0.05). The neural injuries were demonstrated as neural degeneration and necrosis. For evaluating Chinese medicine, a model of vascular dementia in rats is set up with the lacunar stroke from self-thrombosis during hypercholesterolemia. This model from lacunar stroke is useful to investigate the pathogenesis and treatment of vascular dementia.

Effect of exercise-induced neurogenesis on cognitive function deficit in a rat model of vascular dementia.

Chronic cerebral hypoperfusion (CCH) is strongly correlated with progressive cognitive decline in neurological diseases, such as vascular dementia (VaD) and Alzheimer's disease. Exercise can enhance learning and memory, and delay age-related cognitive decline. However, exercise-induced hippocampal neurogenesis in experimental animals submitted to CCH has not been investigated. The present study aimed to investigate whether hippocampal neurogenesis induced by exercise can improve cognitive deficit in a rat model of VaD. Male Wistar rats (age, 8 weeks; weight, 292±3.05 g; n=12–13/group) were subjected to bilateral common carotid artery occlusion (2VO) or sham-surgery and each group was then subdivided randomly into no exercise and treadmill exercise groups. Exercise groups performed treadmill exercise daily at 15 m/min for 30 min for 4 weeks from the third to the seventh week after 2VO. It was demonstrated that the number of neural progenitor cells and mature neurons in the subgranular zone of 2VO rats was increased by exercise, and cognitive impairment in 2VO rats was attenuated by treadmill exercise. In addition, mature brain-derived neurotrophic factor (BDNF) levels in the hippocampus were increased in the exercise groups. Thus the present study suggests that exercise delays cognitive decline by the enhancing neurogenesis and increasing BDNF expression in the context of VaD.

Rannasangpei Is a Therapeutic Agent in the Treatment of Vascular Dementia.

Rannasangpei (RSNP) is used as a therapeutic agent in the treatment of cardiovascular diseases, neurological disorders, and neurodegeneration in China; however, its potential use in the treatment of vascular dementia (VD) was unclear. In this study, our aim was to examine the neuroprotective effect of RSNP in a VD rat model, which was induced by permanent bilateral common carotid artery occlusion (2VO). Four-week administration with two doses of RSNP was investigated in our study. Severe cognitive deficit in the VD model, which was confirmed in Morris water maze (MWM) test, was significantly restored by the administration of RSNP. ELISA revealed that the treatments with both doses of RSNP could reinstate the cholinergic activity in the VD animals by elevating the production of choline acetyltransferase (ChAT) and reducing the acetylcholinesterase (AChE); the treatment of RSNP could also reboot the level of superoxide dismutase (SOD) and decrease malondialdehyde (MDA). Moreover, Western blot and quantitative PCR (Q-PCR) results indicated that the RSNP could suppress the apoptosis in the hippocampus of the VD animals by increasing the expression ratio of B-cell lymphoma-2 (Bcl-2) to Bcl-2-associated X protein (Bax). These results suggested that RSNP might be a therapeutic agent in the treatment of vascular dementia in the future.

Effect of selective serotonin reuptake inhibitors on expression of 5-HT1AR and neurotransmitters in rats with vascular dementia.

5-hydroxytryptamine receptor 1A (5-HT1AR) is closely associated with cognitive functions. Selective serotonin reuptake inhibitors (SSRIs) can protect individuals from brain damage following ischemia/hypoxia. To investigate the function of SSRIs in vascular dementia (VD), we established a rat model of VD, and observed the effect of SSRIs on the expression of 5-HT1AR mRNA and neurotransmitters. Male SD rats (6 months) were randomly assigned into sham, model, and SSRI groups (N = 30). VD was achieved by permanent ligation of the bilateral common carotid artery. Escitalopram, a highly selective 5-HT reabsorption inhibitor, was ip injected into the rats for three consecutive weeks. The Morris water-maze was used to test learning and memory. H&E staining for neuronal injury was conducted on cortical and hippocampal tissues. HPLC was used to determine the levels of dopamine (DA), 5-HT, and norepinephrine (NE). RT-PCR was used to determine expression of 5-HT1AR mRNA. As compared to control rats, model animals demonstrated elongated escape latency, lower platform crossing times, and significant injuries to hippocampal CA1 neurons. This was accompanied by reductions in DA, 5-HT, and NE levels in hippocampal tissues, as well as reduced cortical 5-HT and decreased 5-HT1AR mRNA expression (P < 0.05). Escitalopram treatments reduced escape latency, elevated platform crossing times, improved CA1 neuronal damage, increased DA and 5-HT levels in hippocampal and cortical neurons, as well as elevated expression of 5-HT1AR mRNA (P < 0.05). Therefore, SSRIs may improve cognitive dysfunction of VD rats, possibly by stimulating expression of neurotransmitters and protecting neurons.

Paeoniflorin improves regional cerebral blood flow and suppresses inflammatory factors in the hippocampus of rats with vascular dementia.

To explore the delayed neuroprotection induced by paeoniflorin (PF), the principal component of Paeoniae radix prescribed in Chinese medicine, and its underlying mechanisms in rats subjected to vascular dementia (VD). A rat model of VD was induced by bilateral common carotid arteries occlusion (BCCAO). Low-dose or high-dose PF (20 or 40 mg/kg once per day) was administrated for 28 days after VD. The behavioral analysis of rat was measured by water morris. Regional cerebral blood volume (rCBV), regional cerebral blood flflow (rCBF) and mean transit time (MTT) were measured in the bilateral hippocampus by perfusion-weighted imaging (PWI). The levels of interleukin-1β (IL-1β), interleukin-6 (IL-6), and tumor necrosis factor alpha (TNF-α) were measured by commercially available enzyme-linked immunosorbent assay kits. Protein levels were evaluated by western blot analysis. mRNA levels were evaluated by real time-polymerase chain reaction. Western blotting was used to estimate p65 translocation. The behavioral analysis showed that PF could decrease the escape latency time (P<0.05), and increase the residence time of the original platform quadrant and the across platform frequency in water maze in VD rats (P<0.05). Likewise, PF remarkably promoted the rCBV (P<0.05), rCBF and decreased per minute MTT (P<0.05) in hippocampus of VD rats. Furthermore, PF decreased the release of IL-1β, IL-6 and TNF-α as well as inhibited the mRNA expression of IL-1β, IL-6 and TNF-α in the hippocampus of VD rats (P<0.05 or P<0.01). PF also could decrease the protein expressions of inducible nitric oxide synthase and cyclooxygenase-2 in the hippocampus of VD rats (P<0.05 or P<0.01). In addition, PF signifificantly inhibited the nuclear factor κB (NF-κB) pathway in the hippocampus of VD rats. PF signifificantly attenuates cognitive impairment, improves hippocampus perfusion and inhibits inflflammatory response in VD rats. In addition, the anti-inflflammatory effects of PF might be due to inhibiting the NF-κB pathway. PF may be a potential clinical application in improving VD.

Repetitive transcranial magnetic stimulation enhances spatial learning and synaptic plasticity via the VEGF and BDNF–NMDAR pathways in a rat model of vascular dementia

This study aimed to evaluate the effects of repetitive transcranial magnetic stimulation (rTMS) on learning and memory in a rat model of vascular dementia (VaD) and to analyze the associated mechanisms. Bilateral carotid artery occlusion (2-VO) was used to establish a rat model of VaD. High-frequency (5Hz) rTMS was performed on rats for four weeks. Spatial learning and memory abilities were evaluated using the Morris water maze (MWM), and synaptic plasticity in the hippocampus was assessed via long-term potentiation (LTP). Hippocampal expression of vascular endothelial growth factor (VEGF), brain-derived neurotrophic factor (BDNF) and three subunits of the N-methyl-d-aspartic acid receptor (NMDAR), NR1, NR2A and NR2B, was analyzed by Western blotting. Compared with the VaD group, escape latency was decreased (P<0.05) and the time spent in the target quadrant and the percentage of swimming distance within that quadrant were increased (P<0.05) in the rTMS group. LTP at hippocampal CA3-CA1 synapses was enhanced by rTMS (P<0.05). VEGF expression was up-regulated following 2-VO and was further increased by rTMS (P<0.05). BDNF, NR1 and NR2B expression was decreased in the VaD group and increased by rTMS (P<0.05). There were no significant differences in NR2A expression among the three groups. These results suggest that rTMS improved learning and memory in the VaD model rats via the up-regulation of VEGF, BDNF and NMDARs. In addition, NR2B may be more important than NR2A for LTP induction in the hippocampus during rTMS treatment of VaD.

Involuntary, Forced and Voluntary Exercises Equally Attenuate Neurocognitive Deficits in Vascular Dementia by the BDNF-pCREB Mediated Pathway.

A rat model of vascular dementia was used to compare the effects of involuntary exercise induced by functional electrical stimulation (FES), forced exercise and voluntary exercise on the recovery of cognitive function recovery and its underlying mechanisms. In an involuntary exercise (I-EX) group, FES was used to induce involuntary gait-like running on ladder at 12m/min. A forced exercise group (F-EX) and a voluntary exercise group (V-EX) exercised by wheel running. The Barnes maze was used for behavioral assessment. Brain-derived neurotrophic factor (BDNF), phosphorylated extracellular signal-regulated kinase 1 and 2 (ERK1/2) and cAMP response element binding protein (CREB) positive cells in hippocampal CA1, CA2/3 and dentate gyrus (DG) regions were evaluated using immunohistochemical methods. Western blotting was used to assess the levels of BDNF, phosphorylated protein kinase B (Akt), tropomyosin receptor kinase B (TrkB), mitogen-activated protein kinase 1 and 2 (MEK1/2), ERK1/2 and CREB in BDNF-pCREB signaling in the hippocampus and prefrontal cortex. Involuntary, forced and voluntary exercises were all found to reverse the cognitive deficits of vascular dementia with about equal effectiveness. The number of BDNF, pCREB and pERK1/2 immunopositive cells was significantly increased in the hippocampal CA1, CA2/3 and DG regions in all three exercise groups. In addition, involuntary exercise activated BDNF and the phosphorylation of Akt, TrkB, MEK1/2, ERK1/2 and CREB in the hippocampus and prefrontal cortex equally as well as voluntary or forced exercise. These results suggest that involuntary exercise induced by FES may be as beneficial for alleviating cognitive deficits after cerebral ischemia.

Comparison of two programs for quantification of 1H MR spectra of rat brain using a vascular dementia model

Abstract The quantification of in vivo 1H magnetic resonance (MR) spectra measured from the rat brains provides important information about the brain metabolite concentrations and can help to understand the role of the metabolites under normal and pathological conditions. The purpose of this study was to compare the most frequently used algorithms for quantification of 1H spectra: LCModel (Linear Combination of Model spectra) and QUEST (QUantitation based on QUantum ESTimation) from jMRUI software (Java based Magnetic Resonance User Interface). The comparison was done on a rat model of vascular dementia (VD). The MR spectra were measured on 4.7T spectrometer with ultra-short echo time by sequence SPECIAL. For these types of spectra the contribution from the macromolecules and lipids is large. Our analysis revealed that all values determined by QUEST, except for one value, were lower in comparison to values obtained by LCModel. The minimal differences were found in N-acetylaspartate/(phospho) creatine (−0.3 %) and maximal in inositol in both control and VD rats. This underestimation of a metabolite concentration in QUEST may be caused by an overestimation of baseline. Although our study found the different values of metabolite concentrations by these two methods, the quantified metabolite changes in pathological brain were comparable in both analyses.

Effects of Hydrogen Sulfide on Modulation of Theta-Gamma Coupling in Hippocampus in Vascular Dementia Rats.

Our previous study showed that hydrogen sulfide (H2S) could alleviate the cognitive deficits in vascular dementia (VD) rats associated with the improvement of synaptic plasticity. Neural oscillations are reported to interact with each other through either identical-frequency or cross-frequency coupling. This study examined whether impaired neural couplings could be alleviated by H2S in the hippocampal CA3-CA1 of VD rats and explored its possible mechanism. A VD rat model was established by two-vessel occlusion. Sodium hydrosulfide (NaHS), a kind of H2S donor, was administered intraperitoneally (5.6 mg/kg/day) for 3 weeks. Local field potentials were simultaneously collected in the hippocampal CA3 and CA1. The effects of NaHS on the modulation of theta-gamma coupling were evaluated by using the measurements of both phase-phase coupling and phase-amplitude coupling, while several other approaches including behavior, electrophysiology, western blot, immunofluorescence staining were also employed. The results showed that NaHS significantly prevented spatial learning and memory impairments (p < 0.01). NaHS considerably alleviated the impairment of neural coupling in VD rats in an identical-frequency rhythm and between cross-frequency bands. Moreover, the expression of cystathionine-β-synthase (CBS) was markedly attenuated in VD rats. NaHS elevated the expression of CBS to maintain the intrinsic balance of H2S. Interestingly, it was observed that NaHS increased the protein expression of N-methyl-D-aspartic acid receptor 2A (NMDAR2A) in VD rats. In conclusion, the data suggest that NaHS played the neuroprotective role partly via modulating the expression of NMDAR2A in order to alleviate the impairments of neural couplings in VD rats.

마자인(麻子仁)이 치매병태모델의 운동과 인지기능에 미치는 실험적 연구

마자인(麻子仁)이 치매병태모델의 운동과 인지기능에 미치는 실험적 연구

Global Gene Expression Profile of the Hippocampus in a Rat Model of Vascular Dementia.

Vascular dementia (VD) has been one of the most serious public health problems worldwide. It is well known that cerebral hypoperfusion is the key pathophysiological basis of VD, but it remains unclear how global genes in hippocampus respond to cerebral ischemia-reperfusion. In this study, we aimed to reveal the global gene expression profile in the hippocampus of VD using a rat model. VD was induced by repeated occlusion of common carotid arteries followed by reperfusion. The rats with VD were characterized by deficit of memory and cognitive function and by the histopathological changes in the hippocampus, such as a reduction in the number and the size of neurons accompanied by an increase in intercellular space. Microarray analysis of global genes displayed up-regulation of 7 probesets with genes with fold change more than 1.5 (P < 0.05) and down-regulation of 13 probesets with genes with fold change less than 0.667 (P < 0.05) in the hippocampus. Gene Ontology (GO) and pathway analysis showed that the up-regulated genes are mainly involved in oxygen binding and transport, autoimmune response and inflammation, and that the down-regulated genes are related to glucose metabolism, autoimmune response and inflammation, and other biological process, related to memory and cognitive function. Thus, the abnormally expressed genes are closely related to oxygen transport, glucose metabolism, and autoimmune response. The current findings display global gene expression profile of the hippocampus in a rat model of VD, providing new insights into the molecular pathogenesis of VD.

Protective effects of tao-Hong-si-wu decoction on memory impairment and hippocampal damage in animal model of vascular dementia.

Tao-Hong-Si-Wu decoction (TSD) as a traditional chinese medicine (TCM) has been developed to treat thrombotic diseases for hundreds of years, and vascular dementia (VD) is a cognitive dysfunction syndrome caused by cerebral embolism. In this study, the protective effect of TSD on memory impairment and brain damage in rat model of VD induced by middle cerebral artery occlusion (MCAO) was investigated. The study showed that rats in MCAO treatment with TSD for 14 days significantly improved behavioral function, increased densities of neuron, and induced angiogenesis in the brain compared with model rats. TSD also adjusted the neurotransmitter levels, reduced the content of endothelin-1 (ET-1), and induced the activities of vascular endothelial growth factor (VEGF) in hippocampus. Moreover, the immunohistochemical staining and western blotting results also revealed that TSD decreased apoptosis via upregulated B-cell lymphoma-2 (Bcl-2)/Bcl-2 associated X protein (Bax) ratio. These results demonstrated TSD possesses neuroprotective and antidementia properties by preventing the loss of neural cells, adjusting brain neurotransmitter, promoting cerebral blood circulation, and decreasing apoptosis. These results suggested that TSD might be developed as an effective drug for the prevention of VD.