Dementia Rats Research Articles

Hwangryunhaedok-tang Exerts Neuropreventive Effect on Memory Impairment by reducing Cholinergic System Dysfunction and Inflammatory Response in Vascular Dementia Rat Model

Hwangryunhaedok-tang Exerts Neuropreventive Effect on Memory Impairment by reducing Cholinergic System Dysfunction and Inflammatory Response in Vascular Dementia Rat Model

Effect of Long term bilateral and unilateral vestibular stimulation in cogni-tion in scopolamine-induced dementia

The aim of the study is to provide preliminary evidence on beneficial effects of long term caloric vestibular stimulation as an alternative therapy for enhancement of cognition and motor activity as well as delay/prevent dementia symptoms in scopolamine induce dementia in a rat model. Adult male Wistar albino rats were chosen in the current study. Scopolamine was the drug of choice to induce dementia and donepezil was used as a standard drug in this study. Vestibular stimulation method was Caloric vestibular stimulation which was administered by injecting hot water of 45 degrees centigrade into the middle ear cavity with the help of syringe for 60 days (both bilaterally and unilaterally). In conclusion, bilateral and unilateral left vestibular stimulation had found to beneficial in improving spatial memory, motor control and various cognitive neurotransmitter levels in scopolamine-induced dementia rats. But the mechanism is largely unclear and unknown. Further detailed studies should be conducted in this area to explore mechanisms of action.

Effects of pulsed electromagnetic fields on learning and memory abilities of STZ-induced dementia rats

ABSTRACTIntroduction: Recent studies have shown that pulsed electromagnetic field (EMF) has therapeutic potential for dementia, but the associated neurobiological effects are unclear. This study aimed to determine the effects of pulsed EMF on Streptozotocin (STZ)-induced dementia rats.Methods: Forty Sprague-Dawley rats were randomly allocated to one of the four groups: (i) control, (ii) normal saline injection (sham group), (iii) STZ injection (STZ group) and (iv) STZ injection with pulsed EMF exposure (PEMF, 10 mT at 20 Hz) (STZ + MF group). Morris water maze was used to assess the learning and memory abilities. Insulin growth factors 1 and 2 (IGF-1 and IGF-2) gene expression were determined by quantitative PCR. Results: The results showed that the mean escape latency in STZ-induced dementia rats was reduced by 66% under the exposure of pulsed EMF. Compared with the STZ group, the swimming distance and the time for first crossing the platform decreased by 55 and 41.6% in STZ + MF group, respectively. Furthermore, the IGF-2 gene expression significantly increased compared to that of the STZ group. Conclusions: Our findings indicate that the pulsed EMF exposure can improve the ability of learning and memory in STZ-induced dementia rats and this effect may be related to the process of IGF signal transduction, suggesting a potential role for the pulsed EMF for the amelioration of cognition impairment.

Safflower yellow attenuates learning and memory deficits in amyloid β-induced Alzheimer's disease rats by inhibiting neuroglia cell activation and inflammatory signaling pathways.

Safflower yellow (SY) is an aqueous extract of natural safflower. Our laboratory has reported protective effects of alleviating memory impairment with SY in a transgentic mouse model of Alzheimer's disease. The possible beneficial effects of SY on amyloid-β-induced neuroinflammation in dementia remain unclarified. This study we hypothesize that astrocytes and microglia may cause amyloid-β deposition and produce a neuroinflammatory response, aims to explain the role and mechanism of SY in regulating glial activation and reducing Aβ deposition in Aβ1-42 induced rat model. Wistar rats were treated with SY for one month after bilateral hippocampal injection of aggregated Aβ1-42; behavioral tests were performed to demonstrate the amelioration of cognitive function. After that, the contents of iNOS, IL-1β, IL-6, and TNF-α in AD brain was detected. Western blot and real-time PCR were used to detect the M1 and M2-associated markers to demonstrate the activation of microglia. The conducted experiments have revealed that SY could strengthen spatial learning and memory ability of dementia rats, decrease the contents of iNOS, IL-1β, IL-6, and TNF-α and depress the activation of glial cells. Moreover, the SY treatment inhibited the M1 release of pro-inflammatory cytokines (iNOS and CD86), increased the expression of arginase-1, CD206, and YM-1 thereby reduced inflammation in model rats. Thus our results indicated that SY has very important theoretical and clinical value for the research and development of Chinese medicine for the treatment of AD.

Ginsenoside compound K attenuates cognitive deficits in vascular dementia rats by reducing the Aβ deposition

Ginsenoside compound K (CK) is the main metabolite of protopanaxadiol-type ginsenosides and has been demonstrated to exert neuroprotective and cognition-enhancing effects. The effects of CK on cognitive function in vascular dementia (VD) has not been elucidated. Therefore, the present study aims to elucidate the effects of CK on memory function as well as its potential mechanism in VD rats. Sprague–Dawley rats were subjected to Chronic Cerebral Hypoperfusion (CCH) by permanent bilateral common carotid artery occlusion (2VO). CCH induced neuronal damage and aggravated the aggregation of Amyloid-β1-42 peptides (Aβ1-42), which plays a critical role in the neurotoxicity and cognitive impairment. CK treatment attenuated CCH-induced Aβ1-42 deposition and ameliorated cognition impairment. Furthermore, CK enhanced the activity of the pSer9-Glycogen synthase kinase 3β (pSer9-GSK3β) and the insulin degrading enzyme (IDE), which mainly involved the production and clearance of Aβ1-42. Moreover, CK treatment enhanced the activity of protein kinase B (PKB/Akt), a key kinase in phosphatidylinositol 3 kinase (PI3K)/Akt pathway that can regulate the activity of GSK-3β and IDE. In short, our findings provide the first evidence that CK might attenuate cognitive deficits and Aβ1-42 deposition in the hippocampus via enhancing the expression of pSer9-GSK-3β and IDE.

Hwangryunhaedok-Tang Exerts Neuropreventive Effect on Memory Impairment by Reducing Cholinergic System Dysfunction and Inflammatory Response in a Vascular Dementia Rat Model.

Hwangryunhaedok-tang (HRT) is a traditional oriental herbal formula used in Asian countries for treating inflammatory diseases and controlling fever. Our present study aimed to determine whether HRT has therapeutic effects for patients with vascular dementia (VaD) using a bilateral common carotid artery occlusion (BCCAO) rat model and assessing spatial memory impairment and activation of neuroinflammation. BCCAO was performed in male Sprague Dawley rats to induce VaD, and oral HRT was administered daily for 30 d. Our data showed that HRT ameliorated BCCAO-induced memory and cognitive impairment in behavioral tests. In addition, HRT reversed cholinergic dysfunction and neuronal damage in the hippocampus of BCCAO rats. Furthermore, HRT attenuated microglial activation and reduced the phosphorylation of p38 mitogen-activated protein kinase and c-Jun N-terminal kinase (JNK) induced by BCCAO. Simultaneous high-performance liquid chromatography analysis of HRT using index compounds from the herbal composition revealed that both HRT ethanol extract and commercial HRT granules primarily comprise geniposide, baicalin, and berberine. Our study showed that HRT administration resulted in the prevention of neuronal injury induced by BCCAO through improvement of cholinergic dysfunction and inhibition of neuroinflammatory responses, suggesting that HRT may have potential as a treatment for VaD.

Dietary oils ameliorate aluminum chloride-induced memory deficit in wistar rats

Background: Alzheimer's disease (AD) is a progressive neurodegenerative disorder of the brain and is the most common form of dementia. There is no known cure for AD, and therefore, alternate therapies are warranted. Multiple reports state that nutritional or dietary interventions may have therapeutic potential and particularly associating high intake of n-3 polyunsaturated fatty acids to reduce risk for AD. In this direction, we have attempted to study the neuroprotective effects of dietary supplementation with canola oil, olive oil and rice bran oil in an aluminum chloride (AlCl3)-induced dementia model in Wistar rats. Materials and Methods: In the present study, spatial memory of AlCl3-treated animals, given supplementation with dietary oils, was evaluated using the Morris water maze. In addition, brain antioxidant parameters, acetylcholinesterase activity and serum biochemical markers were evaluated at the end of the study. Results: All dietary oils used in the present study showed ameliorative effect on the decline in spatial memory due to AlCl3treatment. However, among the three oils, canola oil exerted the most protective effect toward AlCl3-induced neuronal damage by improving spatial memory and brain antioxidant status. Apart from serum glucose, none of the biochemical parameters were altered by AlCl3or by dietary oil supplementation. Conclusion: The study highlights the protective effect of dietary oils rich in unsaturated fats against Alzheimer's dementia. Canola oil showed highest neuroprotective activity against AlCl3-induced dementia in rats. Abbreviation used: AD: Alzheimer's disease; ALA: Alpha-linoleic acid; DHA: Docosahexaenoic acid; PUFA: Polyunsaturated fatty acids; MWM: Morris water maze; AchE: Acetylcholinesterase; UFAW: University Federation for Animal Welfare.

Cigarette smoking and vascular dementia in rats: Relationships with oxidative stress

Cigarette smoking and vascular dementia in rats: Relationships with oxidative stress

Determination of experimentally given homocysteine causes to alzheimer-like dementia in rats on the basis of different parameters

Determination of experimentally given homocysteine causes to alzheimer-like dementia in rats on the basis of different parameters

Cepharanthine promotes the effect of dexmedetomidine on the deposition of β-amyloid in the old age of the senile dementia rat model by regulating inflammasome expression.

The present study evaluates the synergistic effect of cepharanthine (CP) with dexmedetomidine (DEM) on the deposition of β-amyloid (Aβ) in the brain tissue of senile dementia (SD) rats. Senile dementia was induced by injecting D-gal intraperitoneally 60 mg/kg/day for six weeks and Aβ1-42 (5 µl) intracranially. The effect of cepharanthine and dexmedetomidine was estimated by determining the cognitive function and neurological function score. Moreover, mediators of inflammation, parameters of oxidative stress and reactive oxygen species (ROS) were determined in the brain tissue of senile dementia rats. Mitochondrial membrane permeability and deposition of Aβ1-42 was estimated in senile dementia rats. Western blot assay and reverse transcription polymerase chain reaction (RT-PCR) was performed for the expression of proteins and genes in the brain tissue of senile dementia rats. Data of the study reveal that cepharanthine alone and in combination with dexmedetomidine improves the neurological function score and cognitive function in SD rats. Moreover, parameters of oxidative stress, inflammatory mediators and production of ROS in CP, DEM and CP + DEM treated groups were compared to the SD group of rats. Treatment with CP, DEM and CP + DEM ameliorates the altered expression of NLRP3 pathway and deposition of Aβ in the brain tissue of SD rats. In conclusion, data reveal that cepharanthine ameliorates the deposition of Aβ and NLRP3 pathway in SD rats. Moreover, cepharanthine treatment with dexmedetomidine shows the synergistic effect against the aged SD rat model.

Oxiracetam ameliorates cognitive deficits in vascular dementia rats by regulating the expression of neuronal apoptosis/autophagy-related genes associated with the activation of the Akt/mTOR signaling pathway.

Oxiracetam (ORC) is a commonly used nootropic drug for improving cognition and memory impairments. The therapeutic effect and underlying mechanism of ORC in vascular dementia (VaD) treatment remain unknown. In this study, 3-month-old male Sprague-Dawley rats with permanent bilateral common carotid artery occlusion-induced VaD were treated orally with low (100 mg/kg) or high (200 mg/kg) dose ORC once a day for 4 weeks. The results of the Morris water maze test and Nissl staining showed that ORC treatment significantly alleviated learning and memory deficits and neuronal damage in rats with VaD. Mechanistically, the protein levels of a panel of genes associated with neuronal apoptosis (Bcl-2, Bax) and autophagy (microtubule-associated protein 1 chain 3, Beclin1, p62) were significantly altered by ORC treatment compared with VaD, suggesting a protective role of ORC against VaD-induced neuronal apoptosis and autophagy. Moreover, the Akt/mTOR pathway, which is known to be the upstream signaling governing apoptosis and autophagy, was found to be activated in ORC-treated rats, suggesting an involvement of Akt/mTOR activation in ORC-rendered protection in VaD rats. Taken together, this study demonstrated that ORC may alleviate learning and memory impairments and neuronal damage in VaD rats by altering the expression of apoptosis/autophagy-related genes and activation of the Akt/mTOR signaling pathway in neurons.

Zerumbone promotes proliferation of endogenous neural stem cells in vascular dementia by regulating Notch signalling.

Present investigation determines the effect of zerumbone on the proliferation of stem cells in vascular dementia (VD) rats. Vascular dementia was induced by cerebral ischemia and reperfusion through non-invasive clamp. Rats were treated with zerumbone 50 mg/kg and 100 mg/kg intraperitoneally 30 min for four weeks after the surgery. Cognitive functions are determined by the Morris water maze (MWM) test and neurological function score in VD rats. Moreover mediators of inflammation and parameters of oxidative stress were estimated in the brain tissue homogenate of ischemia-induced vascular dementia rats. The expression of proteins and mRNA expressions were determined by western blot assay and RT-PCR methods. Moreover histopathological changes were observed by H&E staining on the brain tissue of vascular dementia rats. There was a significant reduction in the cognitive function and neurological score in the zerumbone-treated group compared to the VD group of rats. Data of the study reveal that treatment with zerumbone attenuates the altered level of cytokines and markers of oxidative stress parameters in the brain tissue of VD rats. The expression of NICD, Hes-1 and Nestin proteins was significantly (p < 0.01) reduced in the brain tissue of the zerumbone-treated group compared to the VD group of rats. There was a significant reduction in the mRNA expression of Notch-1 and Hes-1 in the brain tissue of the zerumbone-treated group compared to the VD group of rats. This study concludes that treatment with zerumbone protects the neuronal injury and ameliorates the cognitive function by stimulating the proliferation of endogenous neural stem cells. Moreover proliferation of neural stem cells was stimulated in zerumbone-treated rats by regulating the Notch signalling.

Fabrication of peptide-linked albumin nanoconstructs for receptor-mediated delivery of asiatic acid to the brain as a preventive measure in cognitive impairment: optimization, in-vitro and in-vivo evaluation

The aim of the study was to evaluate the neuroprotective activity of glutathione (GU)-conjugated asiatic acid (AA) loaded albumin nanoparticles and establishing the drug targeting efficiency (DTE) of GU as a selective ligand for brain-targeted delivery. Albumin nanoparticles were prepared by desolvation technique and optimized using quality by design (QbD) approach. GU was conjugated with nanoparticles by carbodiimide reaction and characterized by its size and zeta potential using dynamic light scattering phenomenon. Dialysis bag technique was employed for in-vitro release study and in-vivo brain targeting efficiency was evaluated in Sprague-Dawley rats (75 mg/kg, i.p.). Neuroprotective activity was evaluated against scopolamine-induced dementia in rats. Resultant brain bioavailability of nanoparticles with 100.2 nm size and 71.59% entrapment efficiency (EE), was found 7-fold higher than AA dispersion with 293% DTE for the brain. Conjugated nanoparticles showed significantly high percentage correct alternation (p < .05), low escape latency time (p < .01), cholinesterase inhibition (p < .01) and ameliorated GU levels (p < .01) as compared to diseased animals. GU showed potential to enhance the brain delivery of AA with ameliorated neuroprotective activity due to enhanced bioavailability. This concept can serve as a platform technology for similar potential neurotherapeutics, whose clinical efficacy is still challenging owing to poor bioavailability.

CZ-7, a new derivative of Claulansine F, ameliorates 2VO-induced vascular dementia in rats through a Nrf2-mediated antioxidant responses.

Vascular dementia (VD) results from accumulated damage in the vascular system, which is characterized by progressive impairments in memory and cognition and is second only to Alzheimer's disease (AD) in prevalence among all types of dementia. In contrast to AD, there is no FDA-approved treatment for VD owing to its multiple etiologies. In this study, we investigated whether CZ-7, a new derivative of Claulansine F (Clau F) with verified neuroprotective activity in vitro, could ameliorate the cognitive impairment of rats with permanent occlusion of bilateral common carotid arteries (2VO) and its potential mechanisms of action. The 2VO rats were orally administered CZ-7 (10, 20, 40 mg/kg) from day 27 to day 53 post-surgery. Morris water maze tests conducted at day 48-51 revealed that CZ-7 administration significantly reduced the escape latency in 2VO rats. After the rats were sacrificed on day 53, morphological studies using Nissl and terminal deoxynucleotidyl transferase dUTP nick end labeling (TUNEL) staining showed that administration of CZ-7 markedly attenuated the pathological changes in CA1-CA3 area of the hippocampus, including neuronal cell loss, nuclear shrinkage, and dark staining of neurons, and significantly decreased the chronic cerebral hypoperfusion-induced cell loss. Klüver-Barrera staining study revealed that CZ-7 administration significantly improved the white matter lesions. 8-OHdG and reactive oxygen species (ROS) immunofluorescent analyses showed that CZ-7 administration significantly decreased oxidative stress in CA1-CA3 area of the hippocampus. Finally, we found that the CZ-7-improved oxidative stress might be mediated via the Nrf2 pathway, evidenced by the double immunofluorescent staining of Nrf2 and the elevation of expression levels of oxidative stress proteins HO-1 and NQO1. In conclusion, CZ-7 has therapeutic potential for VD by alleviating oxidative stress injury through Nrf2-mediated antioxidant responses.

Effect of medicated thread moxibustion on apoptosis of hippocampal neurons in rat models of chronic cerebral ischemic vascular dementia

To investigate the effect of medicated thread moxibustion onapoptosis in hippocampal neuronsin a rat model of chronic cerebral ischemic vascular dementia. A total of 40 male Wistar rats were randomly divided into normal group and sham-operated group (7 rats each), and rat model of chronic cerebral ischemic vascular dementia (14 rats). The model group rats were treated with medicated thread moxibustion two weeks after surgery, once a day, with one day break every six days, (24 times in all)and an observation period of 4 weeks. At the end of therapy, H&amp;E staining was used to monitor changes in the neurons in CA1 area of the rat hippocampus. Changes in related indexes such as Bax, Bc1-2 and C-fos of neuron apoptosis in hippocampus CA1 area were determined by immunohistochemistry, while protein expression was semi-quantitatively assayed using imaging analysis technique. There was significant hippocampal neuronal necrosis six weeks after model establishment, but the necrosis was milder in rats in the medicated thread moxibustion group. Bax and C-fos were positively expressed and significantly higher in the hippocampus of chronic cerebral ischemic vascular dementia rats (model group) than in the medicated thread moxibustion group after treatment (p &lt;0.01). The expression of Bcl-2 was increased in the medicated thread group after treatment, and was higher in the model group, but comparable to that in the sham-operated group (p=0.975&gt;0.05). Medicated thread moxibustion alleviates hippocampal neuronal necrosis, inhibits neuron apoptosis in hippocampus CA1 area, protects nerves, and maintains relative equilibrium inBax/Bcl-2 through down-regulation of C-fos and Bax and up-regulation of Bcl-2. Thus, cell apoptosis-related pathway may be one of its mechanisms of action.

Effects of IL-1β on hippocampus cell apoptosis and learning ability of vascular dementia rats.

Vascular dementia (VD) is a type of memory, cognition, and behavior disorder caused by ischemic stroke or hemorrhagic stroke. It is a common pathogenesis of dementia that is only second to Alzheimer's disease. Inflammation plays a key role in VD. Interleukin-1β (IL-1β) is a kind of pro-inflammatory cytokine, while its mechanism in VD occurrence and development is still unclear. The healthy male rats were randomly divided into three groups, including sham group, VD model group (established by bilateral common carotid artery ligation), and IL-1β group (treated by IL-1β monoclonal antibody intracerebroventricular injection on based on model group). Rat learning ability was evaluated by Morris water maze assay. IL-1β expression in brain tissue and peripheral blood was examined by using Real Time-PCR and enzyme-linked immunosorbent assay (ELISA), respectively. Hippocampus apoptosis was detected by caspase 3 activity detection kit. B-cell lymphoma-2 (Bcl-2) and p38 mitogen-activated protein kinase (MAPK) protein levels were assessed by Western blot assay. IL-1β expression was increased, caspase 3 activity was enhanced, Bcl-2 level was declined, and p-P38 phosphorylation was elevated in brain tissue and peripheral blood from VD model group compared to sham group (p<0.05). IL-1β monoclonal antibody significantly reduced IL-1β expression, improved learning ability, attenuated caspase 3 activity, increased Bcl-2 level, and declined p-P38 expression in VD rats compared to model group (p<0.05). IL-1β can delay VD occurrence and development through the P38-MAPK signaling pathway to regulate cell apoptosis and improve learning ability.

Ameliorative Effect of Silymarin on Scopolamine-induced Dementia in Rats.

AIM:This study aims to elucidate the possible ameliorative effect of silymarin on scopolamine-induced dementia using the object recognition test (ORT) in rats.METHODS:The study was extended to demonstrate the role of cholinergic activity, oxidative stress, neuroinflammation, brain neurotransmitters and histopathological changes in the anti-amnestic effect of silymarin in demented rats. Wistar rats were pre-treated with silymarin (200, 400, 800 mg/kg) or donepezil (10 mg/kg) orally for 14 consecutive days. Dementia was induced after the last drug administration by a single intraperitoneal dose of scopolamine (16 mg/kg). Then behavioural, biochemical, histopathological, and immunohistochemical analyses were then performed.RESULTS:Rats pre-treated with silymarin counteracted scopolamine-induced non-spatial working memory impairment in the ORT and decreased acetylcholinesterase (AChE) activity, reduced malondialdehyde (MDA), elevated reduced glutathione (GSH), restored gamma-aminobutyric acid (GABA) and dopamine (DA) contents in the cortical and hippocampal brain homogenates. Silymarin reversed scopolamine-induced histopathological changes. Immunohistochemical analysis showed that silymarin mitigated protein expression of the glial fibrillary acidic protein (GFAP) and nuclear factor kappa-B (NF-κB) in the brain cortex and hippocampus. All these effects of silymarin were similar to that of the standard anti-amnestic drug, donepezil.CONCLUSION:This study reveals that the ameliorative effect of silymarin on scopolamine-induced dementia in rats using the ORT maybe in part mediated by, enhancement of cholinergic activity, anti-oxidant and anti-inflammatory activities as well as mitigation in brain neurotransmitters and histopathological changes.

Betulinic acid, a natural PDE inhibitor restores hippocampal cAMP/cGMP and BDNF, improve cerebral blood flow and recover memory deficits in permanent BCCAO induced vascular dementia in rats

Vascular dementia (VaD) is the second most common form of senile dementia, embraces memory deficits, neuroinflammation, executive function damage, mood and behavioral changes and abnormal cerebral blood flow. The purpose of the study was to explore the therapeutic potential of betulinic acid in bilateral common carotid artery occlusion (BCCAO) induced VaD in experimental rats. VaD was induced by BCCAO in rats and betulinic acid (10 and 15 mg/kg/day po) was administered 1 week after surgery. The cerebral blood pressure of the animal was recorded before and after the treatment using Laser Doppler flow meter. Object recognition task for non-spatial, Morris water maze for spatial and locomotor activity was performed to evaluate behavioral changes in rats. At the end of the study, animals were decapitated and hippocampus was separated to perform biochemical, neuroinflammatory and second messengers cAMP/cGMP analysis. Histology was done to study the brain pathophysiology. BCCAO surgery was able to significantly impaired memory in rats as observed behavioral and biochemical parameters. Moreover, BA demonstrated a neuroprotective effect in a dose-dependent manner. BA was able to re-establish cerebral blood flow, restore behavioral parameters and showed significant improvements in the as cAMP,cGMP and BDNF levels, restrain the oxidative stress and inflammatory parameters. In histopathology, betulinic acid treated groups showed a decrease in microgliosis and less pathological abnormalities comparable to diseased rat's brain. The observed effect might be attributed to the neuroprotective potential of betulinic acid and its ability to restore cognitive impairment and hippocampal neurochemistry in VaD.

Effect of Pyridoxine on toxicity of Aminoguanidine and its Neuroprotective effect in Aluminum Chloride induced Dementia in rats

Effect of Pyridoxine on toxicity of Aminoguanidine and its Neuroprotective effect in Aluminum Chloride induced Dementia in rats

Anti-oxidative and Anti-apoptotic Effects of Acupuncture: Role of Thioredoxin-1 in the Hippocampus of Vascular Dementia Rats

Emerging evidence suggests that acupuncture treatment has anti-oxidative effects that affect cognitive impairment in vascular dementia (VD) rats. In the present study, we aimed to investigate whether thioredoxin-1 (Trx-1)/thioredoxin reductase-1 (TrxR-1) was involved in the beneficial effects of acupuncture. After 2-weeks of acupuncture treatment, Morris water maze (MWM), dihydroethidium (DHE) staining, Nissl staining and TdT-mediated dUTP nick end labeling (TUNEL) staining were used to assess the effects of acupuncture on cognitive function and hippocampal neuronal injury in two-vessel occlusion (2VO) model. The protein and mRNA levels of Trx-1 and TrxR-1, the activity of TrxR-1 as well as the phosphorylation of the apoptosis signal-regulating kinase 1 (ASK1)-c-Jun N-terminal kinase (JNK)/p38 pathway were measured by Western blot, real-time PCR analysis, TrxR-1 activity analysis and immunofluorescence (IF) staining respectively. We found that there were oxidative and apoptotic injury in the CA1 area, accompanied with the decreased expressions of Trx-1 and TrxR-1 in the hippocampus. Acupuncture ameliorated cognitive deficits caused by cerebral ischemic injury and inhibited oxidative stress and neuronal apoptotic injury in the hippocampus. Acupuncture also up-regulated the expressions of Trx-1 and TrxR-1, increased the activity of TrxR-1, accompanied with inhibiting the activation of the ASK1-JNK/p38 pathway. However, the effects of acupuncture on improving cognitive function, inhibiting oxidative stress and neuron apoptotic damage were blocked by Trx-1siRNA. In conclusion, these findings indicated that acupuncture treatment improved VD though anti-oxidative and anti-apoptotic mechanisms which involved the up-regulations of Trx-1/TrxR-1 and inhibitions of ASK1-JNK/p38 pathway.