Hippocampus Of Vascular Dementia Rats Research Articles

Tongqiao Yizhi granule repress the nuclear factor kappa-b/nucleotide oligomerization domain-like receptors 3/caspase-1 pyroptosis pathway in the hippocampus to counter vascular dementia in rats.

To explore the mechanism by which Tongqiao Yizhi granule (, TQYZKL) intervenes pyroptosis to treat vascular dementia (VaD) in a rat model. The rat model of VaD was established by two-vessel occlusion (2VO). The rats were randomly divided into Sham group, Model group, Nimodipine group, TQYZKL (6.2 g?kg-1?d-1), TQYZKL (12.4 g?kg-1?d-1), TQYZKL (24.8 g?kg-1?d-1). The Morris water maze (MWM) test was carried out to test the learning and memory function; Hematoxylin-eosin staining and transmission electron microscopy (TEM) to observe the pathological damage in the hippocampus; Tunel fluorescence staining to detect neuronal pyroptosis in the hippocampus. The expression levels of pyroptosis-related proteins, namely Golgi peripheral membrane protein p65 (P65), nucleotide oligomerization domain-like receptors 3 (NLRP3), caspase-1 and Gasdermin D (GSDMD), were detected using Western blotting and reverse transcription polymerase chain reaction. Moreover, the serum levels of interleukin-1β (IL-1β) and interleukin-18 (IL-18) were determined through the enzyme-linked immunosorbent assay. The study revealed that TQYZKL effectively improved the ability of VaD ratsto learn and memorize, relieved the pathological damage in the hippocampus, restored neuronal morphology, and reduced the expression of pyroptosis-related proteins P65, NLRP3, caspase-1, GSDMD-N, IL-18 and IL-1β (P < 0.05). TQYZKL inhibits neuronal pyroptosis in the hippocampus of VaD rats by regulating nuclear factor kappa-B/NLRP3/caspase-1 signaling pathway, thus exerting a therapeutic effect on VaD in the rats.

Danggui-Shaoyao San alleviates cognitive impairment via enhancing HIF-1α/EPO axis in vascular dementia rats

Ethnopharmacological relevanceInvigorating blood circulation to remove blood stasis is a primary strategy in TCM for treating vascular dementia (VaD). Danggui-Shaoyao San (DSS), as a traditional prescription for neuroprotective activity, has been proved to be effective in VaD treatment. However, its precise molecular mechanisms remain incompletely understood. Aim of the studyThe specific mechanism underlying the therapeutic effects of DSS on VaD was explored by employing network pharmacology as well as in vivo and in viro experiment validation. Materials and methodsWe downloaded components of DSS from the BATMAN-TCM database for target prediction. The intersection between the components of DSS and targets, PPI network, as well as GO and KEGG enrichment analysis were then performed. Subsequently, the potential mechanism of DSS predicted by network pharmacology was assessed and validated through VaD rat model induced by 2VO operation and CoCl2-treated PC12 cells. Briefly, the DSS extract were first quantified by HPLC. Secondly, the effect of DSS on VaD was studied using MWM test, HE staining and TUNEL assay. Finally, the molecular mechanism of DSS against VaD was validated by Western blot and RT-QPCR experiments. ResultsThrough network analysis, 137 active ingredients were obtained from DSS, and 67 potential targets associated with DSS and VaD were identified. GO and KEGG analysis indicated that the action of DSS on VaD primarily involves hypoxic terms and HIF-1 pathway. In vivo validation, cognitive impairment and neuron mortality were markedly ameliorated by DSS. Additionally, DSS significantly reduced the expression of proteins related to synaptic plasticity and neuron apoptosis including PSD-95, SYP, Caspase-3 and BCL-2. Mechanistically, we confirmed DSS positively modulated the expression of HIF-1α and its downstream proteins including EPO, p-EPOR, STAT5, EPOR, and AKT1 in the hippocampus of VaD rats as well as CoCl2-induced PC12 cells. HIF-1 inhibitor YC-1 significantly diminished the protection of DSS on CoCl2-induced PC12 cell damage, with decreased HIF-1α, EPO, EPOR expression. ConclusionOur results initially demonstrated DSS could exert neuroprotective effects in VaD. The pharmacological mechanism of DSS may be related to its positive regulation on HIF-1α/EPO pathway.

Effects of electroacupuncture on the microvascular structure and related protein expression in the hippocampus of vascular dementia rats.

To explore the effect of electroacupuncture (EA) at "Baihui" (GV20) and "Shenting" (GV24) on the microvascular structure and related protein expression in the hippocampus of vascular dementia (VD) rat model, and to investigate the mechanism of EA in the treatment of VD. A total of 24 SD rats were randomly divided into sham operation, model, EA, and oxiracetam groups, with 6 rats in each group. Multiple cerebral infarction method was used to establish VD model. In the EA group, EA was applied to GV20 and GV24 for 30 min, once daily for 14 days. Rats in the oxiracetam group were treated with oxiracetam (50 mg/kg) by intraperitoneal injection, and the course of treatment was the same as that in the EA group. Learning and memory ability were evaluated by using Morris water maze test and new object recognition experiment. The cerebral blood flow was detected by laser doppler. The microvascular structure in the hippocampus was observed by transmission electron microscopy. The expression of vascular structure related proteins of platelet-derived growth factor receptor (PDGFR)-β, platelet endothelial cell adhesion molecule-1(CD31), neural cadherin N-Cadherin, Zonula occludens protein-1(ZO-1) in the hippocampus were measured by Western blot. Compared with the sham operation group, the rats in the model group had a significant increase in time of first crossing the platform, a significant decrease in the number of crossing platform and the new object preference index (P<0.05), a significant decrease in cerebral blood flow (P<0.05), and a significant increase in the brain weight (P<0.05). The structure boundary of pericyte and endothelial cells in the microvessels of the hippocampal CA1 area of model group was blurred, accompanied by obvious edema around the vessels and the reduction of tight junctions. The protein expression levels of PDGFR-β, CD31, N-Cadherin, ZO-1 were significantly decreased in the model group compared with those in the sham operation group (P<0.05). Compared with the model group, the time of first crossing the platform of rats in the EA and oxiracetam group was shortened, the number of crossing platform were increased (P<0.05), the cerebral blood flow was increased (P<0.05), the brain weight was decreased (P<0.05), the morphology and structure of pericyte and endothelial cells in the microvessels of hippocampal CA1 area were intact, accompanied by the increase of tight junctions. Additionally, Compared with the model group, the EA group had a significant increase in the new object preference index (P<0.05), the protein expression levels of PDGFR-β, CD31, ZO-1 in the EA group were increased (P<0.05), and the expression of PDGFR-β, N-Cadherin, ZO-1 in the oxiracetam group were increased (P<0.05). EA at GV20 and GV24 can improve the learning and memory ability of VD rats, and the mechanism may be related to the repair of microvascular structures and improvement of cerebral blood flow.

Dl-3-n-Butylphthalide Protects against Memory Deficits in Vascular Dementia Rats by Attenuating Pyroptosis via TLR-4/NF-κB Signaling Pathway

Introduction: Inflammation is closely associated with the pathogenesis of vascular dementia (VD). Dl-3-n-butylphthalide (NBP) is a small molecule compound extracted from the seeds of Chinese celery, which have anti-inflammatory properties in animal models of acute ischemia and patients with stroke. In this experiment, we studied the protective effects of NBP in a rat model of VD induced by permanent bilateral occlusion of the common carotid arteries and investigated the role of the TLR-4/NF-κB inflammatory signaling pathway in the pathology of VD. Methods: The Morris water maze test was used to evaluate cognitive deficits in the VD rats. Western blot, immunohistochemistry, and PCR analyses were used to analyze the molecular basis of the inflammatory response. Results: NBP significantly improved the learning and memory ability of VD rats. With regard to the protective mechanism, the results showed that NBP significantly downregulated the relative expression of Cleaved Cas-1/Cas-1 and Cleaved GSDMD/GSDMD. Moreover, NBP decreased the levels of the TLR-4 and NF-κB (P65) protein and phosphorylation of P65 in the hippocampus of VD rats via the TLR-4/NF-κB signaling pathway. Conclusion: These findings demonstrate that NBP protects against memory deficits in permanent bilateral common carotid artery occlusion-induced VD rats by attenuating pyroptosis via the TLR-4/NF-κB signaling pathway.

Naringenin Attenuates Cognitive Impairment in a Rat Model of Vascular Dementia by Inhibiting Hippocampal Oxidative Stress and Inflammatory Response and Promoting N-Methyl-D-Aspartate Receptor Signaling Pathway.

Vascular dementia (VaD) is the second most common form of dementia globally, yet there are no efficient treatments. Naringenin, a natural flavonoid, exerts antioxidative, anti-inflammatory, and neuroprotective properties; however, its potential effect on VaD remain unclear. Herein, the purpose of present study was to elucidate whether naringenin attenuates cognitive dysfunction in VaD via inhibiting hippocampal oxidative stress and inflammatory response, and promoting N-methyl-D-aspartate receptors (NMDARs) signaling pathway. A rat model of VaD was established by permanent bilateral common carotid artery occlusion [2-vessel occlusion (2VO)]. Behavioral performance analyses results revealed that administration of naringenin improves cognitive impairment in rats with VaD according to the new object recognition test and the Morris water maze test. In addition, naringenin attenuated hippocampal oxidative stress by reducing reactive oxygen species generation, decreasing malondialdehyde content and recombinant reactive oxygen species modulator 1 (Romo-1) expression, and increasing superoxide dismutase and glutathione peroxidase activities in the hippocampus of VaD rats. Moreover, naringenin decreased the proinflammatory cytokines (IL-1β, IL-6, and TNF-α) levels and increased the anti-inflammatory cytokines (IL-10 and IL-4) levels in the hippocampus of 2VO surgery-treated rats, attenuating hippocampal inflammatory response during VaD. Furthermore, naringenin promoted synaptophysin (SYP), postsynaptic density protein 95 (PSD95), N-methyl-Daspartic acid receptor 1 (NR1) and N-methyl-D-aspartate receptor subunit 2B (NR2B) expressions levels in hippocampus of VaD rats. Collectively, these findings indicated thatnaringenin mitigates cognitive impairmentin VaD rats partly via inhibiting hippocampal oxidative stress and inflammatory response and restoring NMDARs signaling pathway.

Ligustilide Improves Cognitive Impairment via Regulating the SIRT1/IRE1α/XBP1s/CHOP Pathway in Vascular Dementia Rats.

Vascular dementia (VaD), the second cause of dementia, is caused by chronic cerebral hypoperfusion, producing progressive damage to cerebral cortex, hippocampus, and white matter. Ligustilide (LIG), one of the main active ingredients of Angelica sinensis, exerts the neuroprotective effect on neurodegenerative diseases. However, the mechanism remains unclear. An in vivo model of bilateral common carotid artery occlusion and in vitro model of oxygen glucose deprivation (OGD) were employed in this study. LIG (20 or 40 mg/kg/day) was intragastrically administered to the VaD rats for four weeks. The results of the Morris water maze test demonstrated that LIG effectively ameliorated learning and memory deficiency in VaD rats. LIG obviously relieved neuronal oxidative stress damage by increasing the activities of catalase (CAT), superoxide dismutase (SOD), and glutathione peroxidase (GSH-PX) and decreasing the level of malondialdehyde (MDA) in VaD rats. Nissl staining showed that LIG increased the number of the Nissl body in VaD rats. After LIG administration, the apoptotic-related protein, Bax, was decreased and Bcl-2 was increased in the hippocampus of VaD rats. Moreover, the expressions of sirtuin 1 (SIRT1) and protein disulfide isomerase (PDI) were decreased, binding immunoglobulin protein (BIP) and phospho-inositol-requiring enzyme-1α (P-IRE1α), X-box binding protein 1 (XBP1s), and C/EBP-homologous protein (CHOP) were increased in VaD rats. After LIG treatment, these changes were reversed. The immunofluorescence results further showed that LIG upregulated the expression of SIRT1 and downregulated the expression of P-IRE1α in VaD rats. In addition, in vitro experiment showed that EX-527 (SIRT1 inhibitor) partly abolished the inhibitory effect of LIG on the IRE1α/XBP1s/CHOP pathway. In conclusion, these studies indicated that LIG could improve cognitive impairment by regulating the SIRT1/IRE1α/XBP1s/CHOP pathway in VaD rats.

Effects of ginkgo biloba extract on learning and memory and protection of hippocampal neurons in rats with vascular dementia

Objective To investigate the effects of ginkgo biloba extracts (EGb761) on learning and memory and the protective effect on hippocampal neurons in rats with vascular dementia (VD). Methods Ninety rats were randomly divided into sham-operated group, model group and EGb761-treated group, with 30 rats in each group. Rats in each group were examined at 15 days, 1 month and 2 months, with 10 rats in each time point. VD model was established by bilateral carotid artery occlusion combinding with injection of sodium nitroprusside. Morris water maze test was used to detect the learning and memory function of rats. The expression of glial fibrillary acidic protein (GFAP) was observed by immunofluorescence. Western-blot was used to detect the protein expression of P-glycoprotein (P-GP), excitatory amino acid transporters 2(EAAT2), caspase-3 and cleaved caspase-3.RT-PCR was used to detect the mRNA expression of P-GP and EAAT2 in the hippocampus of rats in each group. Results Compared with sham-operated group, the escape latency (EL) was significantly prolonged at each time point in model group (sham-operated group: 15 days(15.52±3.23)s, 1 month(14.21±2.62)s, 2 months(15.37±1.66)s; model group: 15 days(30.35±2.30)s, 1 month(40.78±3.55)s, 2 months(33.88±1.47)s; all P<0.01). The EL of EGb761-treated group was significantly shorter than that of the model group(EGb761-treated group: 15 days(25.69±2.44)s, 1 month(20.78±1.72)s, 2 months(18.23±1.67)s, all P<0.01). Immunofluorescence showed that the expression of GFAP in EGb761-treated group was lower than that of the model group (P<0.01). Western blot showed that cleaved caspase-3 protein expression in EGb761-treated group at each time point was significantly lower than that in the model group (P<0.01). Western-blot and RT-PCR results showed that the protein and mRNA expression of P-GP and EAAT2 in EGb761-treated group at 15 day and 1 month time points were significant increased than those in the model group (P<0.01). At 2 month time point, which were lower than those in the model group (P<0.01). Conclusion EGb761 can improve the learning and memory ability of VD rats, and regulate the protein and mRNA expression of P-GP and EAAT2 in hippocampus of VD rats at different time points (up-regulated in 1 month and down-regulated in 2 month), and down-regulate the expression of cleaved caspase-3 and GFAP at different time points, thereby delaying the brain damage of VD rats and protecting neurons. Key words: Ginkgo biloba extracts; Vascular dementia rats; P-glycoprotein; Excitatory amino acid transporters 2; Glial fibrillary acidic protein

FoxO1-mediated autophagy plays an important role in the neuroprotective effects of hydrogen in a rat model of vascular dementia

Vascular dementia (VD) is a heterogeneous group of brain disorders in which cognitive impairment is attributed to cerebrovascular pathologies. Autophagy, a self-cannibalization mechanism, has been demonstrated to be involved in VD progression. Molecular hydrogen is known for its powerful anti-oxidative, anti-apoptotic, and anti-inflammatory activities, and it is also involved in autophagy. However, the effects of hydrogen on VD remain unclear. The current study found that hydrogen-rich water (HRW) significantly alleviated spatial learning and memory impairments. Similar to donepezil treatment, HRW also inhibited neuron loss and shrinkage in the hippocampal CA1 region. In addition, we found that HRW significantly increased the Bcl-2/Bax expression ratio and decreased cleaved caspase-3 expression levels in the hippocampus of VD rats. Moreover, electron microscopy revealed that HRW decreased the number of autophagosomes. We also observed that HRW reduced the increased ratio of LC3-II/I and Beclin 1 expression and saliently upregulated p62 expression. Furthermore, FoxO1 (a major mediator of autophagy regulation) and Atg7 levels were apparently decreased in the hippocampus of HRW-treated bilateral common carotid artery occlusion (2VO) rats. Taken together, these data show that molecular hydrogen exerts beneficial effects on cognitive impairment induced by chronic cerebral hypoperfusion. FoxO1-mediated autophagy plays an important role in the neuroprotective effects of hydrogen in a rat model of VD. Furthermore, the present findings highlight that HRW should be further investigated as a new therapeutic strategy for VD treatment in the future.

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.

Puerarin Up-regulates Methyl-CpG Binding Protein 2 Phosphorylation in Hippocampus of Vascular Dementia Rats.

To observe the effect of puerarin on methyl-CpG binding protein 2 (MeCP2) phosphorylation (pMeCP2) in the hippocampus of a rat model of vascular dementia (VD). Thirty-six healthy Sprague-Dawley rats were randomly assigned to the sham-operated group, dementia group and puerarintreated group using a random number table (n=12 per group). The modifified permanent bilateral common carotid artery occlusion method was used to establish the VD model. The sham-operated and dementia groups were given 2 mL/d of saline, while the puerarin-treated group was given 100 mg/(kg•d) of puerarin for 17 days. The learning and memory abilities were evaluated by the Morris water maze test. Hematoxylin-eosin staining, immunohistochemical (IHC) staining and Western blot analysis were carried out to observe changes in neuron morphology and in level of pMeCP2 in the hippocampus, respectively. The morphologies of rat hippocampal neurons in the puerarintreated group were markedly improved compared with the dementia group. The escape latency of the dementia group was significantly longer than the sham-operated group (P<0.05), while the puerarin-treated group was obviously shorter than the dementia group (P<0.05). Cross-platform times of the dementia group were signifificantly decreased compared with the sham-operated group (P<0.05), while the puerarin-treated group was obviously increased compared with the dementia group (P<0.05). IHC staining showed no significant difference in the number of MeCP2 positive cells among 3 groups (P>0.05). The number of pMeCP2 positive cells in the CA1 region of hippocampus in the dementia group was signifificantly increased compared with the sham-operated group, and the puerarin-treated group was signifificantly increased compared with the dementia group (both P<0.05). Western blot analysis showed no signifificant difference of MeCP2 expression among 3 groups (P>0.05). The expression of pMeCP2 in the dementia group was signifificantly increased compared with the sham-operated group, while it in the puerarin-treated group was signifificantly increased compared with the dementia group (P<0.05). Puerarin could play a role in the protection of nerve cells through up-regulating pMeCP2 in the hippocampus, improving neuron morphologies, and enhancing learning and memory ablities in a rat model of VD.

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.

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.

Effect of electroacupuncture on the expression of mTOR and eIF4E in hippocampus of rats with vascular dementia

Clinically, electroacupuncture is proved to be an effective therapy for vascular dementia; however, their mechanisms remain uncertain. The aim of the current study was to investigate the mechanism of electroacupuncture therapy for vascular dementia. One month after a vascular dementia animal model was established by bilateral occlusion of common carotid arteries, electroacupuncture treatment was given at "Baihui" (DU20), "Dazhui" (DU14), and "Shenshu" (BL23). Morris water maze was used to assess the learning and memory ability of rats. Western blot assay was performed to detect the expression of mammalian target of rapamycin (mTOR) and eukaryotic translation initiation factor 4E (eIF4E) in hippocampus of rats. Morris water maze test showed that electroacupuncture improved the learning ability of vascular dementia rats. Western blot assay revealed that the expression level of mTOR and eIF4E in the electroacupuncture group and sham-operated group was higher than that in the vascular dementia group (P < 0.05). In conclusion, the decreasing expression of mTOR and eIF4E plays important roles in the pathogenesis of vascular dementia. Electroacupuncture improves learning and memory ability by up-regulating expression of mTOR and eIF4E in the hippocampus of vascular dementia rats.

Puerarin decreases hypoxia inducible factor-1 alpha in the hippocampus of vascular dementia rats.

In this study, a rat vascular dementia model was established by permanent bilateral common carotid arterial occlusion. Rats were intraperitoneally injected with puerarin 3 days before modeling, for 45 successive days. Results demonstrated that in treated animals hippocampal structures were clear, nerve cells arranged neatly, and cytoplasm was rich in Nissl bodies. The number of cells positive for hypoxia inducible factor-1 alpha, erythropoietin and endothelial nitric oxide synthase was reduced; and the learning and memory abilities of rats were significantly improved. Our experimental findings indicate that puerarin can significantly improve learning and memory in a vascular dementia model, and that the underlying mechanism may be associated with the regulation of the expression of hypoxia inducible factor-1 alpha.