Xiehua Xue

Electroacupuncture improves neurological deficits and enhances proliferation and differentiation of endogenous nerve stem cells in rats with focal cerebral ischemia

Abstract Objectives: This study was carried out to observe the effect of electroacupuncture (EA) on neurological deficits, proliferation and differentiation of nerve stem cells (NSCs) in adult rats with middle cerebral artery occlusion (MCAO) and to study its possible role in the treatment of cerebral ischemic injury. Methods: A rat model of MCAO was established and interfered with EA. On days 4, 7, 14 and 21 after ischemic injury, neurological deficits were scored. On days 4, 7, 14 and 21 after injury, effect of EA interference on the proliferation and differentiation of rat NSCs was observed with BrdU/NeuN and BrdU/GFAP immunofluorescence double labeling. Results: A significant difference was found in the scores of rat neurological deficits between the EA and model groups 7, 14 and 21 days after cerebral ischemic injury (p<0·05). BrdU positive cells were found in the subventricular zone (SVZ) 4, 7, 14 and 21 days after ischemic injury. The number of positive BrdU cells in the SVZ reached its peak 7 days after injury and was greater in the EA group than in the model group 7 and 14 days after injury (p<0·05). The number of BrdU/GFAP doubly labeled positive cells in the SVZ was greater in the EA group than in the model group 7 and 14 days after ischemic injury (p = 0·012 and p = 0·025, respectively). There was no difference in the number of BrdU/NeuN doubly labeled positive cells 4, 7 and 14 days in the striatum, but a significant difference 21 days (p = 0·033) after ischemic injury between the two groups. Discussion: Cerebral ischemic injury induces proliferation of NSCs, some of which will differentiate into both astroglia and neurons. EA may promote cells proliferation, stimulate the proliferating cells to differentiate into astroglia and mature into neurons, which may be one of the important reasons why EA can alleviate neurological deficits.

Electro-acupuncture at points of Zusanli and Quchi exerts anti-apoptotic effect through the modulation of PI3K/Akt signaling pathway

We evaluated the neuroprotective effect of electro-acupuncture (EA) on cerebral ischemia-reperfusion (IR) injury and deeply investigated the relationship between this neuroprotective effect and PI3K/Akt pathway. Rats underwent focal cerebral IR injured by suture method and received the in vivo therapeutic efficacy of EA at points of Zusanli(ST36) and Quchi(LI11) after the operation. We found that the EA treatment significantly (p<0.05) improved neurological deficit and cerebral infarction. Furthermore, EA profoundly activated PI3K/Akt signaling resulted in the inhibition of cerebral cell apoptosis in the ischemic penumbra. Simultaneously EA increased the expression of PI3K, p-Akt, p-Bad and Bcl-2 at the protein level and the expression of Bcl-2 at the mRNA level. On the contrary, EA inhibited the Bax and cleaved Caspase-3-positive expression. The selective PI3K inhibitor LY294002 compromised EA-induced neuroprotective effects and reduced the elevation of p-Akt, p-Bad and Bcl-2 levels. Our data suggested that the PI3K/Akt pathway played a critical role in mediating the neuroprotective effects of EA treatment at points of Zusanli and Quchi after the ischemic stroke.

Increased Hippocampus–Medial Prefrontal Cortex Resting-State Functional Connectivity and Memory Function after Tai Chi Chuan Practice in Elder Adults

Previous studies provide evidence that aging is associated with the decline of memory function and alterations in the hippocampal (HPC) function, including functional connectivity to the medial prefrontal cortex (mPFC). In this study, we investigated if longitudinal (12-week) Tai Chi Chuan and Baduanjin practice can improve memory function and modulate HPC resting-state functional connectivity (rs-FC). Memory function measurements and resting-state functional magnetic resonance imaging (rs-fMRI) were applied at the beginning and the end of the experiment. The results showed that (1) the memory quotient (MQ) measured by the Wechsler Memory Scale-Chinese Revision significantly increased after Tai Chi Chuan and Baduanjin practice as compared with the control group, and no significant difference was observed in MQ between the Tai Chi Chuan and Baduanjin groups; (2) rs-FC between the bilateral hippocampus and mPFC significantly increased in the Tai Chi Chuan group compared to the control group (also in the Baduanjin group compared to the control group, albeit at a lower threshold), and no significant difference between the Tai Chi Chuan and Baduanjin groups was observed; (3) rs-FC increases between the bilateral hippocampus and mPFC were significantly associated with corresponding memory function improvement across all subjects. Similar results were observed using the left or right hippocampus as seeds. Our results suggest that both Tai Chi Chuan and Baduanjin may be effective exercises to prevent memory decline during aging.

Gua Lou Gui Zhi decoction exerts neuroprotective effects on post-stroke spasticity via the modulation of glutamate levels and AMPA receptor expression

Spasticity is one of the most physically debilitating disabilities following stroke and may slow down the potential success of rehabilitation. Glutamate and α-amino-3-hydroxy-5-methyl-4-isoxazolepropionic acid (AMPA) receptors have been shown to play a crucial role in spasticity following cerebral ischemia/reperfusion (I/R) injury. Gua Lou Gui Zhi decoction (GLGZD) is a well-known traditional Chinese formula that has long been used clinically in China to treat muscular spasticity following stroke, epilepsy or spinal cord injury. However, the precise mechanisms behind its neuroprotective and anti-spasticity effects remain poorly understood. In the present study, using a rat model of focal cerebral I/R injury, we evaluated the neuroprotective and anti-spasticity effects of GLGZD and investigated the underlying mechanisms. We found that GLGZD improved neurological deficits and reduced infarct volumes in cerebral I/R-injured rats. In addition, GLGZD reduced cerebral ischemic spasticity since it improved the screen test and Hoffmans reflex (H-reflex) scores. It also reduced glutamate levels in the cerebrospinal fluid and altered the expression of the AMPA receptor subunits. Our data demonstrate that GLGZD exerts neuroprotective and anti-spasticity effects in a cerebral ischemia model via the modulation of glutamate levels and AMPA receptor expression.

Electro-acupuncture at LI11 and ST36 acupoints exerts neuroprotective effects via reactive astrocyte proliferation after ischemia and reperfusion injury in rats

Reactive astrogliosis is a common phenomenon in central nervous system (CNS) injuries such as ischemic stroke. The present study aimed to deeply investigate the relationships between the neuroprotective effect of electro-acupuncture (EA) and reactive astrocytes following cerebral ischemia. EA treatment at the Quchi (LI11) and Zusanli (ST36) acupoints at Day 3 attenuated neurological deficits and cerebral infarct volume in ischemia and reperfusion (I/R) injured rats. Animal behavior assessments found that the speed of Catwalk gait, equilibrium and coordination of Rotarod test were improved. Furthermore, EA treatment exerted neuroprotective effects via activation of glial fibrillary acidic protein (GFAP), vimentin and nestin positive cells. Simultaneously, an obvious increase in GFAP/vimentin, GFAP/nestin and GFAP/BrdU co-labeling appeared in the peri-infract cortex and striatum, suggesting EA can promote the proliferation of GFAP/vimentin/nestin-positive reactive astrocytes. The expression of cell cycle-associated proteins Cyclin Dl, CDK4 and phospho-Rb were increased in the peri-infract cortex and striatum, indicating proliferated reactive astrocytes-mediated CyclinDl/CDK4 regulation of the transition of the G1-to-S cell cycle phases. In addition, EA enhanced the localized expression of brain-derived neurotrophic factor (BDNF) in the peri-infract cortex and striatum. These results demonstrated that EA treatment at the LI11 and ST36 acupoints on Day 3 exerted neuroprotection via proliferation of GFAP/vimentin/nestin-positive reactive astrocytes and, potentially, secretion of reactive astrocytes-derived BDNF in I/R injured rats.

Tai Chi Chuan and Baduanjin practice modulates functional connectivity of the cognitive control network in older adults

Cognitive impairment is one of the most common problem saffecting older adults. In this study, we investigated whether Tai Chi Chuan and Baduanjin practice can modulate mental control functionand the resting state functional connectivity (rsFC) of the cognitive control network in older adults. Participants in the two exercise groups practiced either Tai Chi Chuan or Baduanjin for 12 weeks, and those in the control group received basic health education. Memory tests and fMRI scans were conducted at baseline and at the end of the study. Seed-based (bilateral dorsolateral prefrontal cortex, DLPFC) rsFC analysis was performed. We found that compared to the controls, 1) both Tai Chi Chuan and Baduanjin groups demonstrated significant improvements in mental control function; 2) the Tai Chi Chuan group showed a significant decrease in rsFC between the DLPFC and the left superior frontal gyrus (SFG) and anterior cingulate cortex; and 3) the Baduanjin group showed a significant decrease in rsFC between the DLPFC and the left putamen and insula. Mental control improvement was negatively associated with rsFC DLPFC-putamen changes across all subjects. These findings demonstrate the potential of Tai Chi Chuan and Baduanjin exercises in preventing cognitive decline.

Electroacupunctre improves motor impairment via inhibition of microglia-mediated neuroinflammation in the sensorimotor cortex after ischemic stroke.

AIMS Electroacupuncture (EA) is one of the safety and effective therapies for improving neurological and sensorimotor impairment via blockade of inappropriate inflammatory responses. However, the mechanisms of anti-inflammation involved is far from been fully elucidated. MAIN METHODS Focal cerebral ischemic stroke was administered by the middle cerebral artery occlusion and reperfusion (MCAO/R) surgery. The MCAO/R rats were accepted EA treatment at the LI 11 and ST 36 acupoints for consecutive 3days. The neurological outcome, animal behaviors test and molecular biology assays were used to evaluate the MCAO/R model and therapeutic effect of EA. KEY FINDINGS EA treatment for MCAO rats showed a significant reduction in the infarct volumes accompanied by functional recovery in mNSS outcomes, motor function performances. The possible mechanisms that EA treatment attenuated the over-activation of Iba-1 and ED1 positive microglia in the peri-infract sensorimotor cortex. Simultaneously, both tissue and serum protein levels of the tumor necrosis factor-α (TNF-α), interleukin-1β (IL-1β) and interleukin-6 (IL-6) were decreased by EA treatment in MCAO/R injured rats. The levels of inflammatory cytokine tumor necrosis factor-α (TNF-α), interleukin-1β (IL-1β), interleukin-6 (IL-6) were decreased in the peri-infract sensorimotor cortex and blood serum of MCAO/R injured rats after EA treatment. Furthermore, we found that EA treatment prevented from the nucleus translocation of NF-κB p65 and suppressed the expression of p38 mitogen-activated protein kinase (p38 MAPK) and myeloid differentiation factor 88 (MyD88) in the peri-infract sensorimotor cortex. SIGNIFICANCE The findings from this study indicated that EA improved the motor impairment via inhibition of microglia-mediated neuroinflammation that invoked NF-κB p65, p38 MAPK and MyD88 produced proinflammatory cytokine in the peri-infract sensorimotor cortex of rats following ischemic stroke.

Electroacupuncture protects against ischemic stroke by reducing autophagosome formation and inhibiting autophagy through the mTORC1-ULK1 complex-Beclin1 pathway

In a previous study by our group, we demonstrated that electroacupuncture (EA) activates the class I phosphoinositide 3-kinase (PI3K)/Akt signaling pathway. There is considerable evidence that the downstream mammalian target of rapamycin complex 1 (mTORC1) plays an important role in autophagy following ischemic stroke. The aim of the present study was to determine whether EA exerts a neuroprotective effect through mTORC1-mediated autophagy following ischemia/reperfusion injury. Our results revealed that EA at the LI11 and ST36 acupoints attenuated motor dysfunction, improved neurological deficit outcomes and decreased the infarct volumes. The number of autophagosomes, autolysosomes and lysosomes was decreased following treatment with EA. Simultaneously, the levels of the autophagosome membrane maker, microtubule-associated protein 1 light chain 3 beta (LC3B)II/I, Unc-51-like kinase 1 (ULK1), autophagy related gene 13 Atg13) and Beclin1 (ser14) were decreased, whereas mTORC1 expression was increased in the peri-infarct cortex. These results suggest that EA protects against ischemic stroke through the inhibition of autophagosome formation and autophagy, which is mediated through the mTORC1-ULK complex-Beclin1 pathway.

Effects of Alisma Decoction on lipid metabolism and inflammatory response are mediated through the activation of the LXRα pathway in macrophage-derived foam cells

The liver X receptor α (LXRα)/ATP-binding cassette transporter A1 (ABCA1) pathway and LXR-modulated cytokines play an important role in macrophages which mediate lipid engulfment and the inflammatory response, and participate in the process of atherosclerosis. Therefore, lipid-lowering and anti-inflammatory therapy through the activation of the LXRα/ABCA1 pathway and LXRα-modulated cytokines may prove to be one of the main treatment strategies for atherosclerosis. Alisma Decoction (AD) has long been used in China to clinically treat cardiovascular and cerebral diseases; however, the precise mechanisms involved remain to be elucidated. In the present study, we evaluated the regulation of lipids and the anti-inflammatory effects exerted by AD and investigated the underlying molecular mechanisms using oxidized low-density lipoprotein (ox-LDL)-stimulated foam cells derived from rat peritoneal macrophages. We first found that AD markedly relieved lipid deposition in foam cells as it increased LXRα and ABCA1 expression and decreased the ox-LDL-induced expression of inflammatory cytokines, such as matrix metalloproteinase-9 and interleukin-1β. Collectively, our findings suggest that blocking lipid deposition and inhibiting inflammatory response through the activation of the LXRα pathway may be one of the main mechanisms through which AD exerts its anti-atherosclerotic effects.

Tai Chi Chuan and Baduanjin Increase Grey Matter Volume in Older Adults: A Brain Imaging Study

The aim of this study is to investigate and compare how 12-weeks of Tai Chi Chuan and Baduanjin exercise can modulate brain structure and memory function in older adults. Magnetic resonance imaging and memory function measurements (Wechsler Memory Scale-Chinese revised, WMS-CR) were applied at both the beginning and end of the study. Results showed that both Tai Chi Chuan and Baduanjin could significantly increase grey matter volume (GMV) in the insula, medial temporal lobe, and putamen after 12-weeks of exercise. No significant differences were observed in GMV between the Tai Chi Chuan and Baduanjin groups. We also found that compared to healthy controls, Tai Chi Chuan and Baduanjin significantly improved visual reproduction subscores on the WMS-CR. Baduanjin also improved mental control, recognition, touch, and comprehension memory subscores of the WMS-CR compared to the control group. Memory quotient and visual reproduction subscores were both associated with GMV increases in the putamen and hippocampus. Our results demonstrate the potential of Tai Chi Chuan and Baduanjin exercise for the prevention of memory deficits in older adults.