Cephalic electroacupuncture restores learning and memory in rats with induced ischemic stroke via inhibition of NF-κB nuclear translocation.

Inflammatory responses in the brain contribute to cognitive deficits. Nuclear factor-κB (NF-κB), a critical transcription factor in inflammatory responses, is activated in post-stroke cognitive deficit. Baihui (DU20) and Shenting (DU24) acupoints, the main acupoints of Du Meridian, are widely used to improve cognitive deficits in Chinese patients with stroke. It has been reported that post-stroke cognitive deficits can be treated by electroacupuncture (EA) but the underlying mechanisms of these effects are unclear. Using the rat middle cerebral artery occlusion cerebral ischemia-reperfusion injury model, we found that EA at these 2 acupoints improved neurological function, decreased cerebral infarct lesion volumes, and ameliorated the inflammatory response in the hippocampal CA1 region. The treatment also ameliorated memory and learning deficits by inhibiting the NF-κB signaling pathway in the ischemic hippocampal CA 1 region. This coincided with downregulation of interleukin-1ß, interleukin-6, CD45, and tumor necrosis factor-α. We conclude that EA at these 2 acupoints ameliorates memory and learning deficits following experimental cerebral infarction by inhibiting NF-κB-mediated inflammatory injury in the hippocampal CA1 region.

Effects of Virtual Reality Rehabilitation Training on Cognitive Function and Activities of Daily Living of Patients With Poststroke Cognitive Impairment: A Systematic Review and Meta-Analysis.

OBJECTIVE: To determine the effects of virtual reality (VR) rehabilitation training on the cognitive function and activities of daily living (ADL) of patients with poststroke cognitive impairment (PSCI). DATA SOURCES: Four Chinese databases and 6 English databases were systematically searched for studies published until August 31, 2021, by using Medical Subject Headings of the National Library of Medicine terms such as virtual reality, cognition disorders, cognitive dysfunction, and stroke and free terms such as virtual environment, VR, cognition impairment, cerebrovascular accident, and PSCI. STUDY SELECTION: Randomized controlled trials treating PSCI with VR training were included. The control groups received conventional treatments such as conventional rehabilitation training and drug therapy; the experimental groups received VR rehabilitation training. The outcome measures were cognitive function and ADL. DATA EXTRACTION: Two researchers independently extracted key information from eligible studies. The methodological quality of the studies was evaluated using the Cochrane Handbook for Systematic Reviews of Interventions v5.1.0. Meta-analysis was performed using RevMan v5.4. We followed the Preferred Reporting Items for Systematic Reviews and Meta-Analyses 2020 guidelines. DATA SYNTHESIS: Twenty-one studies (1149 participants) were included. Meta-analyses found that compared with the control group, VR rehabilitation training increased Mini-Mental State Examination, Montreal Cognitive Assessment, Loewenstein Occupational Therapy Cognitive Assessment, Rivermead Behavioral Memory Test Second Edition, Barthel Index, Modified Barthel Index, and FIM scores; event-related potential 300 (P300) amplitude; and the N-acetylaspartate/creatinine (Cr) ratio on proton magnetic resonance spectroscopy (1H-MRS) and reduced P300 latency; Trail Making Test scores; and the choline-containing compounds/Cr ratio on 1H-MRS (all P<.05). These results indicated that VR training improved cognitive function and ADL in PSCI. CONCLUSIONS: VR rehabilitation training promotes the rehabilitation of cognitive function and recovery of ADL in patients with PSCI and may be a good complementary approach to conventional cognitive interventions.

Electroacupuncture Ameliorates Cognitive Impairment Through the Inhibition of NLRP3 Inflammasome Activation by Regulating Melatonin-Mediated Mitophagy in Stroke Rats.

Previous studies found that electroacupuncture (EA) at the Shenting (DU24) and Baihui (DU20) acupoints alleviates cognitive impairment in cerebral ischemia-reperfusion (I/R) injury rats. Nonetheless, the mechanisms of the anti-inflammatory effects of EA are unclear. Cerebral I/R injury was induced in rats by middle cerebral artery occlusion (MCAO). Following I/R injury, the rats underwent EA therapy at the Shenting (DU24) and Baihui (DU20) acupoints for seven successive days. The Morris water maze test, magnetic resonance imaging (MRI) and molecular biology assays were utilized to assess the establishment of the rat stroke model with cognitive impairment and the therapeutic effect of EA. EA treatment of rats subjected to MCAO showed a significant reduction in infarct volumes accompanied by cognitive recovery, as observed in Morris water maze test outcomes. The possible mechanisms by which EA treatment attenuates cognitive impairment are by regulating endogenous melatonin secretion through aralkylamine N-acetyltransferase gene (AANAT, a rate-limiting enzyme of melatonin) synthesis in the pineal gland in stroke rats. Simultaneously, through melatonin regulation, EA exerts neuroprotective effects by upregulating mitophagy-associated proteins and suppressing reactive oxygen species (ROS)-induced NLRP3 inflammasome activation after I/R injury. However, melatonin receptor inhibitor (luzindole) treatment reversed these changes. The findings from this research suggested that EA ameliorates cognitive impairment through the inhibition of NLRP3 inflammasome activation by regulating melatonin-mediated mitophagy in stroke rats.

Electroacupuncture Improves Synaptic Function in SAMP8 Mice Probably via Inhibition of the AMPK/eEF2K/eEF2 Signaling Pathway.

Synaptic loss and dysfunction is associated with cognitive impairment in Alzheimer's disease (AD). Recent evidence indicates that the AMP-activated protein kinase (AMPK)/eukaryotic elongation factor-2 kinase (eEF2K)/eukaryotic elongation factor-2 (eEF2) pathway was implicated in synaptic plasticity in AD. Therapeutic strategies for AD treatment are currently limited. Here, we investigate the effects of electroacupuncture (EA) on synaptic function and the AMPK/eEF2K/eEF2 signaling pathway in male senescence-accelerated mouse-prone 8 (SAMP8) mice. Male 7-month-old SAMP8 and SAMR1 mice (senescence-accelerated mouse resistant 1) were randomly divided into 3 groups: SAMR1 control group (Rc), SAMP8 control group (Pc), and SAMP8 electroacupuncture group (Pe). The Pe group was treated with EA for 30 days. Transmission electron microscopy (TEM) was used to observe the structure of synapse. The protein and mRNA expression of synaptophysin (SYN) and postsynaptic density 95 (PSD95) was examined by immunohistochemistry, western blot, and real-time RT-PCR. The activity of AMPK and eEF2K was studied by western blot. Our results showed that EA ameliorated synaptic loss, increased the expression of SYN and PSD95, and inhibited AMPK activation and eEF2K activity. Collectively, these findings suggested that the mechanisms of EA improving synaptic function in AD may be associated with the inhibition of the AMPK/eEF2K/eEF2 signaling pathway.

Tougu Xiaotong capsule exerts a therapeutic effect on knee osteoarthritis by regulating subchondral bone remodeling.

Previous studies have shown that Tougu Xiaotong capsule (TGXTC) has therapeutic effects on knee osteoarthritis (OA) through multiple targets. However, the mechanisms of action underlying its regulation of subchondral bone reconstruction remain unclear. In this study, we investigated the effects of TGXTC on subchondral bone remodeling. Eighteen six-month-old New Zealand white rabbits of average sex were randomly divided into the normal, model and TGXTC groups. The rabbit knee OA model was induced by a modified Hulth's method in the model and TGXTC groups, but not the normal group. Five weeks postoperatively, intragastric administration of TGXTC was performed for four weeks. After drug administration, the medial femoral condyle and tibia were prepared for observation of cartilage histology via optical microscopy and micro-computed tomography, the serum was collected for biochemical parameters assay and the subchondral bone isolated from the lateral femoral condyle was collected for detection of IL-1ß and TNF-α mRNA and protein by reverse transcription-quantitative polymerase chain reaction and western blot analysis, respectively. The results showed that treatment with TGXTC significantly mitigated cartilage injury and subchondral bone damage, improved the parameter of subchondral trabecular bone, decreased alkaline phosphatase and tartrate-resistant acid phosphatase activity, and significantly reducing the osteoprotegerin/receptor activator of nuclear factor-κB ligand ratio, reduced the expression of IL-1ß and TNF-α mRNA and protein. These results suggest that TGXTC could delay the pathological development of OA by regulating subchondral bone remodeling through regulation of bone formation and bone resorption and its relating inflammatory factors, and this may partly explain its clinical efficacy in the treatment of knee OA.

Electroacupuncture ameliorates cognitive impairment through inhibition of Ca2+-mediated neurotoxicity in a rat model of cerebral ischaemia-reperfusion injury.

BACKGROUND: The hippocampus is vulnerable to severe damage after cerebral ischaemia-reperfusion (I/R) injury. This study aimed to explore the effect of electroacupuncture (EA) on cognitive impairment and its relationship with Ca2+neurotoxicity in a rat model of I/R injury induced by middle cerebral artery occlusion (MCAO). METHODS: 60 adult male Sprague-Dawley rats were randomly divided into three groups: control (sham surgery) group, untreated MCAO group and EA-treated MCAO+EA group. Rats in the MCAO and MCAO+EA groups underwent modelling of poststroke cognitive impairment by MCAO surgery. EA was performed for 30 min daily at GV20 and GV24 (1-20 Hz) for 1 week. The Morris water maze experiment was used to assess cognitive function. 2,3,5-triphenyl tetrazolium chloride staining was used to measure infarct volume. The intracellular Ca2+content in the Cornu Ammonis (CA)1 area of the hippocampus was assessed by laser confocal scanning microscopy. ELISA was performed to evaluate the concentration of glutamate (Glu) in the hippocampus, and the protein expression of two Glu receptors (N-methyl-D-aspartic acid receptor (NMDAR) 2A and NMDAR2B) were analysed by Western blotting. RESULTS: Compared with the untreated MCAO group, EA effectively ameliorated cognitive impairment (P=0.01) and shrunk the infarct volume (P=0.032). The content of intracellular Ca2+, Glu and NMDAR2B in the hippocampus was significantly raised by MCAO (P=0.031-0.043), while EA abrogated these effects. NMDAR2A was decreased by MCAO (P=0.015) but increased by EA (P=0.033). CONCLUSIONS: EA had a beneficial effect on cognitive repair after cerebral I/R, and its mechanism of action likely involves a reduction of Ca2+influx via inhibition of Glu neurotoxicity and downregulation of NMDAR2B expression.

Electroacupuncture ameliorate learning and memory by improving N-acetylaspartate and glutamate metabolism in APP/PS1 mice.

OBJECTIVE: To explore the precise mechanism of electroacupuncture (EA) to delay cognitive impairment in Alzheimer disease. METHODS: N-Acetylaspartate (NAA), glutamate (Glu) and myoinositol (mI) metabolism were measured by magnetic resonance spectroscopy, learning and memory of APP/PS1 mouse was evaluated by the Morris water maze test and the step-down avoidance test, neuron survival number and neuronal structure in the hippocampus were observed by Nissl staining, and BDNF and phosphorylated TrkB detected by Western blot. RESULTS: EA at DU20 acupuncture significantly improve learning and memory in behavioral tests, up-regulate NAA, Glu and mI metabolism, increase the surviving neurons in hippocampus, and promote the expression of BDNF and TrkB in the APP/PS1 transgenic mice. CONCLUSION: These findings suggested that EA is a potential therapeutic for ameliorate cognitive dysfunction, and it might be due to EA could improve NAA and Glu metabolism by upregulation of BDNF in APP/PS1 mice.

Electroacupuncture ameliorate learning and memory by improving N -acetylaspartate and glutamate metabolism in APP/PS1 mice

OBJECTIVE: To explore the precise mechanism of electroacupuncture (EA) to delay cognitive impairment in Alzheimer disease. Methods N -Acetylaspartate (NAA), glutamate (Glu) and myoinositol (mI) metabolism were measured by magnetic resonance spectroscopy, learning and memory of APP/PS1 mouse was evaluated by the Morris water maze test and the step-down avoidance test, neuron survival number and neuronal structure in the hippocampus were observed by Nissl staining, and BDNF and phosphorylated TrkB detected by Western blot. RESULTS: EA at DU20 acupuncture significantly improve learning and memory in behavioral tests, up-regulate NAA, Glu and mI metabolism, increase the surviving neurons in hippocampus, and promote the expression of BDNF and TrkB in the APP/PS1 transgenic mice. CONCLUSION: These findings suggested that EA is a potential therapeutic for ameliorate cognitive dysfunction, and it might be due to EA could improve NAA and Glu metabolism by upregulation of BDNF in APP/PS1 mice.

Electro-acupuncture ameliorates cognitive impairment via improvement of brain-derived neurotropic factor-mediated hippocampal synaptic plasticity in cerebral ischemia-reperfusion injured rats.

A previous study by our group found that electro-acupuncture (EA) at the Shenting (DU24) and Baihui (DU20) acupoints ameliorates cognitive impairment in rats with cerebral ischemia-reperfusion (I/R) injury. However, the precise mechanism of action has remained largely unknown. The present study investigated whether brain-derived neurotropic factor (BDNF) mediates hippocampal synaptic plasticity as the underlying mechanism. Rats were randomly divided into three groups: The sham operation control (Sham) group, the focal cerebral ischemia-reperfusion (I/R) group, and the I/R with EA treatment (I/R+EA) group. The I/R+EA group received EA treatment at the Shenting (DU24) and Baihui (DU20) acupoints after the operation. EA treatment was found to ameliorate neurological deficits (P<0.05) and reduce the cerebral infarct volume (P<0.01). In addition, EA improved cognitive function in cerebral I/R-injured rats (P<0.05). Furthermore, EA treatment promoted synaptic plasticity. Simultaneously, EA increased the hippocampal expression of BDNF, its high-affinity tropomyosin receptor kinase B (TrkB) and post-synaptic density protein-95 (PSD-95) in the rats with cerebral I/R injury. Collectively, the findings suggested that BDNF-mediated hippocampal synaptic plasticity may be one mechanism via which EA treatment at the Shenting (DU24) and Baihui (DU20) acupoints improves cognitive function in cerebral I/R injured rats.

Electroacupuncture attenuates learning and memory impairment via activation of α7nAChR-mediated anti-inflammatory activity in focal cerebral ischemia/reperfusion injured rats.

Studies have reported that electroacupuncture (EA) may reduce learning and memory impairment following cerebral ischemic injury. However, the precise mechanism of action remains unclear. In the present study, the attenuation of focal cerebral ischemia/reperfusion injury by EA in rats was investigated. EA at the Baihui (DU 20) and Shenting (DU 24) acupoints was demonstrated to significantly improve performance in the Morris water maze task, with shortened latency time and increased frequency of passing the platform. Molecular analysis revealed that EA activated the expression of α7 nicotinic acetylcholine receptors (α7nAChR) in the hippocampus. In addition, EA led to a decreased expression of the microglia/macrophage marker Iba1 and the astrocyte marker glial fibrillary acidic protein in the hippocampus. EA treatment also led to decreased production of the inflammatory cytokines tumor necrosis factor-α and interleukin-1ß. Treatment with methyllycaconitine, an α7nAChR antagonist, attenuated the improvement of learning and memory following EA treatment and the inhibitory effects of EA on glial cell activation and inflammatory cytokine production. In conclusion, the findings of the present study demonstrate that EA is able to improve learning and memory function following cerebral ischemic injury via activation of α7nAChR, which significantly decreases the neuroinflammatory response.

Activation of brain glucose metabolism ameliorating cognitive impairment in APP/PS1 transgenic mice by electroacupuncture.

An essential feature of Alzheimer's disease (AD) is implicated in brain energy metabolic impairment that is considered underlying pathogenesis of cognitive impairment. Therefore, therapeutic interventions to allay cognitive deficits that target energy metabolism may be an efficacy strategy in AD. In this study, we found that electroacupuncture (EA) at the DU20 acupoint obviously increased glucose metabolism in specific brain regions such as cortex, hippocampus, cingulate gyrus, basal forebrain septum, brain stem, and cerebellum in APP/PS1 transgenic mice by animal 18F-Fluoro-2-deoxy-D-Glucose (18F-FDG)/positron emission tomography (PET) imaging, accompanied by cognitive improvements in the spatial reference learning and memory and memory flexibility and novel object recognition performances. Further evidence shown energy metabolism occurred in neurons or non-neuronal cells of the cortex and hippocampus in terms of the co-location of GLUT3/NeuN and GLUT1/GFAP. Simultaneously, metabolic homeostatic factors were critical for glucose metabolism, including phosphorylated adenosine monophosphate-activated protein kinase (AMPK) and AKT serine/threonine kinase. Furthermore, EA-induced phosphorylated AMPK and AKT inhibited the phosphorylation level of the mammalian target of rapamycin (mTOR) to decrease the accumulation of amyloid-beta (Aß) in the cortex and hippocampus. These findings are concluded that EA is a potential therapeutic target for delaying memory decline and Aß deposition of AD. The AMPK and AKT are implicated in the EA-induced cortical and hippocampal energy metabolism, which served as a contributor to improving cognitive function and Aß deposition in a transgenic mouse model of AD.

Polyphenol-Inspired Facile Construction of Smart Assemblies for ATP- and pH-Responsive Tumor MR/Optical Imaging and Photothermal Therapy.

Smart assemblies have attracted increased interest in various areas, especially in developing novel stimuli-responsive theranostics. Herein, commercially available, natural tannic acid (TA) and iron oxide nanoparticles (Fe3 O4 NPs) are utilized as models to construct smart magnetic assemblies based on polyphenol-inspired NPs-phenolic self-assembly between NPs and TA. Interestingly, the magnetic assemblies can be specially disassembled by adenosine triphosphate, which shows a stronger affinity to Fe3 O4 NPs than that of TA and partly replaces the surface coordinated TA. The disassembly can further be facilitated by the acidic environment hence causing the remarkable change of the transverse relaxivity and potent "turn-on" of fluorescence (FL) signals. Therefore, the assemblies for specific and sensitive tumor magnetic resonance and FL dual-modal imaging and photothermal therapy after intravenous injection of the assemblies are successfully employed. This work not only provides understandings on the self-assembly between NPs and polyphenols, but also will open new insights for facilely constructing versatile assemblies and extending their biomedical applications.

Electroacupuncture Regulates Hippocampal Synaptic Plasticity via miR-134-Mediated LIMK1 Function in Rats with Ischemic Stroke.

MircoRNAs (miRs) have been implicated in learning and memory, by regulating LIM domain kinase (LIMK1) to induce synaptic-dendritic plasticity. The study aimed to investigate whether miRNAs/LIMK1 signaling was involved in electroacupuncture- (EA-) mediated synaptic-dendritic plasticity in a rat model of middle cerebral artery occlusion induced cognitive deficit (MICD). Compared to untreatment or non-acupoint-EA treatment, EA at DU20 and DU24 acupoints could shorten escape latency and increase the frequency of crossing platform in Morris water maze test. T2-weighted imaging showed that the MICD rat brain lesions were located in cortex, hippocampus, corpus striatum, and thalamus regions and injured volumes were reduced after EA. Furthermore, we found that the density of dendritic spine and the number of synapses in the hippocampal CA1 pyramidal cells were obviously reduced at Day 14 after MICD. However, synaptic-dendritic loss could be rescued after EA. Moreover, the synaptic-dendritic plasticity was associated with increases of the total LIMK1 and phospho-LIMK1 levels in hippocampal CA1 region, wherein EA decreased the expression of miR-134, negatively regulating LIMK1 to enhance synaptic-dendritic plasticity. Therefore, miR-134-mediated LIMK1 was involved in EA-induced hippocampal synaptic plasticity, which served as a contributor to improving learning and memory during the recovery stage of ischemic stroke.

Suppressive effects of Gua Lou Gui Zhi decoction on MCAO-induced NO and PGE2 production are dependent on the MAPK and NF-κB signaling pathways.

The present study aimed to investigate the inhibitory effects, and underlying mechanisms, of Gua Lou Gui Zhi decoction (GLGZD) in a rat model of neuroinflammation. Sprague-Dawley rats were treated with GLGZD following middle cerebral artery occlusion (MCAO). Neurological function and infarct volume were evaluated to confirm successful generation of the rat model. Subsequently, brain tissues and blood samples were collected for further analysis. Nitric oxide (NO) and prostaglandin E2 (PGE2) were evaluated in peripheral blood samples using the Griess reagent assay and an ELISA, respectively. The relative expression levels of inducible nitric oxide synthase (iNOS) and cylooxygenase­2 (COX­2) were detected by quantitative polymerase chain reaction and immunohistochemistry. The associated pathways, including nuclear factor­κB (NF­κB) and mitogen­activated protein kinases (MAPK) signaling pathways, were detected by electrophoretic mobility shift assay and western blotting. The results demonstrated that treatment with GLGZD significantly inhibited MCAO-induced inflammation; GLGZD suppressed the production of NO and PGE2, and the expression of iNOS and COX­2, by inhibiting NF­κB activation and MAPK phosphorylation. These findings suggest that GLGZD, a potential agent for post­stroke treatment, may exert anti­inflammatory effects, thus providing neuroprotection.

Electroacupuncture improves cognitive ability following cerebral ischemia reperfusion injury via CaM-CaMKIV-CREB signaling in the rat hippocampus.

The aim of the present study was to investigate the effect of electroacupuncture (EA) on cognitive deficits, and the underlying mechanism following cerebral ischemia-reperfusion (I/R) via the calmodulin (CaM)-calmodulin-dependent protein kinase type IV (CaMKIV)-cyclic adenosine monophosphate response elements binding protein (CREB) intracellular signaling pathway in the hippocampus. In total, 45 adult female Sprague-Dawley rats were randomly divided into three groups, namely the sham group, the middle cerebral artery occlusion (MCAO) group and the MCAO + EA group. Rats in the MCAO and MCAO + EA groups were modeled for post-stroke cognitive impairment. EA was performed at the Baihui and Shenting acupuncture points for 30 min/day for one week in the MCAO + EA group. Behavioral testing was analyzed using a step-down apparatus, while 2,3,5-triphenyl tetrazolium chloride was used to detect the infarct volume and lesion size. In addition, CaM activity was assessed by cyclic nucleotide-dependent phosphodiesterase analysis, and the protein expression levels of CaM, CaMKIV, phosphorylated (p)-CaMKIV, CREB and p-CREB were analyzed by western blot analysis. The cerebral I/R injured rat model in the MCAO group was established successfully with regard to the infarct volume and neuronal lesion size, as compared with the sham group. EA was demonstrated to effectively improve the cognitive ability, as measured by the step-down apparatus test, and decrease the infarct volume when compared with the MCAO group (P<0.05). The step-down apparatus test for the EA-treated rats revealed improved learning and reduced memory impairment when compared with the MCAO group. Furthermore, CaM activity and CaM protein expression levels in the MCAO + EA group were lower compared with those in the MCAO group (P<0.05). By contrast, the protein expression levels of CaMKIV, p-CaMKIV, CREB and p-CREB were significantly reduced in the MCAO group when compared with the sham group (P<0.05), although the expression levels increased following EA treatment when compared with the MCAO group (P<0.05). Therefore, cognitive repair benefited from EA, and the main intracellular signaling pathway in the hippocampus was mediated by CaM-CaMKIV-CREB. EA effectively inhibited the expression and activity of CaM, while further enhancing the expression of CaMKIV and CREB, and their associated phosphorylated functions.

Electroacupuncture ameliorates post-stroke learning and memory through minimizing ultrastructural brain damage and inhibiting the expression of MMP-2 and MMP-9 in cerebral ischemia-reperfusion injured rats.

The aim of the present study was to investigate the potential neuroprotective effects of electroacupuncture (EA) in the treatment of cerebral ischemia/reperfusion (I/R) injury, and to elucidate the association between this neuroprotective effect and brain ultrastructure and expression of matrix metalloproteinase (MMP)­2 and 9. Rats underwent focal cerebral I/R injury by arterial ligation and received in vivo therapeutic EA at the Baihui (DU20) and Shenting (DU24) acupoints. The therapeutic efficacy was then evaluated following the surgery. The results of the current study demonstrated that EA treatment significantly ameliorated neurological deficits and reduced cerebral infarct volume compared with I/R injured rats. Furthermore, EA improved the learning and memory ability of rats following I/R injury, inhibited blood brain barrier breakdown and reduced neuronal damage in the ischemic penumbra. Furthermore, EA attenuated ultrastructural changes in the brain tissue following ischemia and inhibited MMP­2/MMP­9 expression in cerebral I/R injured rats. The results suggest that EA ameliorates anatomical deterioration, and learning and memory deficits in rats with cerebral I/R injury.

Electroacupuncture improves cognitive function through Rho GTPases and enhances dendritic spine plasticity in rats with cerebral ischemia-reperfusion.

The aim of the present study was to evaluate the effect of electroacupuncture (EA) on cognitive function following cerebral ischemia­reperfusion (I/R) injury, and to clarify the mechanism through which Rho GTPase is associated with EA analgesia modulation of dendritic spine plasticity. Rats were randomly divided into three groups: The sham surgery group, the middle cerebral artery occlusion (MCAO) model of ischemia group, and the MCAO with EA (MCAO+EA) treatment group. The MCAO+EA group received treatment with EA at points of Baihui (DU20) and Shenting (DU24) following surgery. It was demonstrated that treatment with EA significantly (P<0.05) protected the cognitive function of rats from impairment caused by cerebral I/R injury. Furthermore, EA treatment increased the density of dendritic spines in the hippocampus of cerebral I/R­injured rats. Simultaneously, EA increased the expression of cell division cycle 42, Ras­related C3 botulinum toxin substrate 1 and F­actin proteins. By contrast, EA treatment inhibited the expression of Ras homologous member A. Collectively, these findings suggest that Rho GTPases and dendritic spine plasticity are critical in mediating the effects of EA treatment at the points of Shenting and Baihui, and that EA protects against impairment of cognitive function following ischemic stroke.

Electroacupuncture at the Baihui acupoint alleviates cognitive impairment and exerts neuroprotective effects by modulating the expression and processing of brain-derived neurotrophic factor in APP/PS1 transgenic mice.

Alzheimer's disease (AD) is a common human neurodegenerative disorder characterized by progressive deterioration of cognition and memory. Acupuncture at the Baihui (DU20) acupoint has long been used in China to clinically treat cognitive impairment. However, the precise mechanism underlying its neuroprotective effects remains to be elucidated. In the present study, electroacupuncture (EA) at the Baihui (DU20) acupoint was observed to markedly ameliorate cognitive impairments, reduce the aberrant overexpression of ß-amyloid(1-42), and inhibit neuronal apoptosis in APP/PS1 mice. As brain-derived neurotrophic factor (BDNF) has been implicated in the pathogenesis of AD, the expression and processing of BDNF in APP/PS1 mice was investigated. EA at the Baihui (DU20) acupoint was indicated to significantly enhance the expression levels of mature BDNF and proBDNF in APP/PS1 mice. Furthermore, an increase in the BDNF/proBDNF ratio, upregulation of the expression levels of phosphorylated tropomyosin receptor kinase B and a decrease in the expression level of p75 neurotrophin receptor were also observed in the APP/PS1 mice. The present study demonstrates the efficacy of EA at the Baihui (DU20) acupoint in the treatment of cognitive impairments in APP/PS1 transgenic mice. The present study hypothesized that modulation of BDNF expression and processing may be the underlying mechanism by which stimulation of the Baihui (DU20) acupoint exerts its neuroprotective effect.

Protective effects of the Tougu Xiaotong capsule on morphology and osteoprotegerin/nuclear factor-κB ligand expression in rabbits with knee osteoarthritis.

The imbalance of subchondral bone remodeling is a common pathological feature in the progression of osteoarthritis. In the current study, using a rabbit model of knee osteoarthritis, the effects of the Tougu Xiaotong capsule (TGXTC) on the cartilage and subchondral bone were investigated. In addition, osteoprotegerin (OPG), an inducer of bone formation, and receptor activator of nuclear factor­κB ligand (RANKL), a regulator of bone resorption in the subchondral bone, were assessed, in order to further explore the protective role of TGXTC in subchondral bone remodeling. The rabbit model of knee osteoarthritis, which was induced by a modified version of Hulth's method, was treated with TGXTC or glucosamine hydrochloride for 4 or 8 weeks. Subsequently, the tibia and femur were harvested for observation of cartilage histology, and the subchondral bone was observed by scanning electron microscopy. The expression levels of OPG and RANKL at the gene and protein levels were determined by reverse transcription­quantitative polymerase chain reaction and western blotting. TGXTC and glucosamine hydrochloride were identified to mitigate cartilage injury, reduce trabecular number and thickness and accelerate trabecular separation. It was additionally observed that the level of OPG mRNA and protein expression was reduced, and the RANKL mRNA and protein expression level was increased, in addition to the observation of a lower OPG/RANKL ratio in the TGXTC and hydrochloride groups. Taken together, these results suggest that TGXTC may mitigate cartilage injury and subchondral sclerosis, thus delaying the pathological development of osteoarthritis. This is suggested to be mediated partly through the reduction of OPG expression and increase of RANKL expression, which reduces the OPG/RANKL ratio, suppressing excessive bone formation.