Vagus nerve stimulation in cerebral stroke:biological mechanisms,therapeutic modalities,clinical applications,and future directions

Stroke is a major disorder of the central nervous system that poses a serious threat to human life and quality of life.Many stro ke victims are left with long-term neurological dysfunction,which adversely affects the well-being of the individual and the broader socioeconomic impact.Currently,poststroke brain dysfunction is a major and difficult area of treatment.Vagus nerve stimulation is a Food and Drug Administration-approved exploratory treatment option for autis m,refractory depression,epilepsy,and Alzheimer’s disease.It is expected to be a novel therapeutic technique for the treatment of stroke owing to its association with multiple mechanisms such as alte ring neurotransmitters and the plasticity of central neuro ns.In animal models of acute ischemic stroke,vagus nerve stimulation has been shown to reduce infarct size,reduce post-stroke neurological damage,and improve learning and memory capacity in rats with stroke by reducing the inflammatory response,regulating bloodbrain barrier permeability,and promoting angiogenesis and neurogenesis.At present,vagus nerve stimulation includes both invasive and non-invasive vagus nerve stimulation.Clinical studies have found that invasive vagus nerve stimulation combined with rehabilitation therapy is effective in im proving upper limb motor and cognitive abilities in stroke patients.Further clinical studies have shown that non-invasive vagus nerve stimulation,including ear/ce rvical vagus nerve stimulation,can stimulate vagal projections to the central nervous system similarly to invasive vagus nerve stimulation and can have the same effect.In this paper,we first describe the multiple effects of vagus nerve stimulation in stroke,and then discuss in depth its neuroprotective mechanisms in ischemic stroke.We go on to outline the res ults of the current major clinical applications of invasive and non-invasive vagus nerve stimulation.Finally,we provide a more comprehensive evaluation of the advantages and disadvantages of different types of vagus nerve stimulation in the treatment of cerebral ischemia and provide an outlook on the developmental trends.We believe that vagus nerve stimulation,as an effective treatment for stroke,will be widely used in clinical practice to promote the recovery of stroke patients and reduce the incidence of disability.

Use of 3-D magnetic resonance electrical impedance tomography in detecting human cerebral stroke: a simulation study

We have developed a new three dimensional (3-D) conductivity imaging approach and have used it to detect human brain conductivity changes corresponding to acute cerebral stroke. The proposed Magnetic Resonance Electrical Impedance Tomography (MREIT) approach is based on the J-Substitution algorithm and is expanded to imaging 3-D subject conductivity distribution changes. Computer simulation studies have been conducted to evaluate the present MREIT imaging approach. Simulations of both types of cerebral stroke, hemorrhagic stroke and ischemic stroke, were performed on a four-sphere head model. Simulation results showed that the correlation coefficient (CC) and relative error (RE) between target and estimated conductivity distributions were 0.9245±0.0068 and 8.9997%±0.0084%, for hemorrhagic stroke, and 0.6748±0.0197 and 8.8986%±0.0089%, for ischemic stroke, when the SNR (signal-to-noise radio) of added GWN (Gaussian White Noise) was 40. The convergence characteristic was also evaluated according to the changes of CC and RE with different iteration numbers. The CC increases and RE decreases monotonously with the increasing number of iterations. The present simulation results show the feasibility of the proposed 3-D MREIT approach in hemorrhagic and ischemic stroke detection and suggest that the method may become a useful alternative in clinical diagnosis of acute cerebral stroke in humans.

Perioperative massive cerebral stroke in thoracic patients:Report of three cases

BACKGROUNDPerioperative stroke is a rare but devastating complication. The risk factors formassive cerebral stroke in surgical patients include older age, male sex, priorcerebrovascular disease, hypertension, renal failure, smoking, diabetes mellitus,and atrial fibrillation.CASE SUMMARYWe describe two cases of perioperative massive cerebral stroke following thoracicsurgery and one case following bronchoscopy. Neurologic symptoms, includingchanges in mental status and hemiplegia, occurred within 10 h after surgery in thethree patients. All three patients died after the surgery.CONCLUSIONPerioperative massive cerebral stroke may be more likely to occur in thoracicsurgical patients if there are pre-existing factors including previous stroke,hypotension, and hypoxemia. Sufficient pain control after surgery and timelyneurology consultation and management are helpful for the diagnosis and controlof stroke in high-risk patients.

Functional magnetic resonance imaging evaluation of brain function reorganization in cerebral stroke patients after constraint-induced movement therapy

In this study, stroke patients received constraint-induced movement therapy for 3 weeks. Before and after constraint-induced movement therapy, the flexibility of their upper limbs on the affected side was assessed using the Wolf motor function test, and daily use of their affected limbs was assessed using the movement activities log, and cerebral functional reorganization was assessed by functional magnetic resonance imaging. The Wolf motor function test score and the movement activities log quantity and quality scores were significantly increased, while action performance time in the Wolf motor function test was significantly decreased after constraint-induced movement therapy. By functional magnetic resonance imaging examination, only scattered activation points were visible on the affected side before therapy. In contrast, the volume of the activated area was increased after therapy. The activation volume in the sensorimotor area was significantly different before and after therapy, and the activation area increased and appeared adjusted. In addition to the activated area around the lesions being decreased, there were also some new activated areas, including the supplementary movement area, premotor area and the ipsilateral sensorimotor area. Our findings indicate that constraint-induced movement therapy significantly improves the movement ability and daily use of the affected upper limbs in stroke patients and promotes cerebral functional reorganization.

Mortality Prognostics during First 24 Hours Due to Cerebral Stroke among Adult Population of Rostov-on-Don

In the present research, the model of mortality prognostics during the first 24 hours due to ACA （acute cerebrovascular accident） was developed. Eleven characteristics, developed by logistic regression method, were offered. The present model allows to predict the result ＂died/survived＂ for every adult patient with cerebral stroke, who was delivered to hospital to choose individual approach. And in such way, it raised the effectiveness of treatment and lowered the frequency of fatal case. External causes among solar, geomagnetic and meteorological were defined, which reflected the varied impact of environment and raised of fatal case probability during the first 24 hours.

Nanotechnology-based therapeutics: new hope for ischemic cerebral stroke intervention

Ischemic cerebral stroke is a leading cause of death and disability globally.At present,thrombolytics,such as recombinant tissue-type plasminogen activator,are the only effective treatment for acute stroke.However,usage of thrombolytics has a strict therapeutic window and cannot be applied to a number of patients.Despite the promising effects of some neuroprotectants in preclinical studies,they failed in clinical trials as a result of poor pharmacokinetic properties,particularly with regard to solubility and permeability across the blood-brain barrier(BBB).Approaches for delivering these drugs by nanotechnologies may overcome these pharmacokinetic deficits and enhance their neuroprotective effects.However,issues such as potential side effects and biosafety properties currently limit clinical application of these approaches.In this article,we reviewed recent progress of nanotechnology-based interventions for stroke treatment,and in particular,summarized novel materials applied to synthesize nanocarriers,encapsulation with neuroprotectants,and factors impacting nanodrug bioactivities to provide a theoretical basis for the development of anti-stroke drugs.

Autophagy Elicits Neuroprotection at the Subacute Phase of Transient Cerebral Ischaemia but Has Few Effects on Neurological Outcomes After Permanent Ischaemic Stroke in Rats

Objective Autophagy was prominently activated by cerebral ischaemia.This study was to investigate the exact role of autophagy in ischaemic stroke.Methods Two rat models of transient middle cerebral artery occlusion(tMCAO)and permanent MCAO(pMCAO)were prepared.The brain tissues in the penumbra were obtained to observe the dynamic variations of autophagy activity with Beclin1 and LC3 antibodies by Western blotting.At the characteristic time points,when autophagy activity was markedly elevated or reduced,the autophagy activation signaling was intervened with rapamycin and 3-methyladenine,respectively.Thereafter,key proteins in the autopahgic/lysosomal pathway were detected with the antibodies of LC3,p62,ubiquitin,LAMP-1 and cathepsin B.Meanwhile,TTC staining,neurological score and immunofluorescence were performed to evaluate brain infarct volume,neurological deficit and neuron survival,respectively.Results Both Beclin1 and LC3 expression levels were remarkably altered at 6 h,12 h,2 days and 7 days after tMCAO.Interestingly,the dynamic changes of autophagy activity following pMCAO were identical to those after tMCAO.Neither autophagy induction nor autophagy inhibition was able to ameliorate the pMCAO-induced neurological injury due to lysosomal dysfunction,as indicated by low levels of LAMP-1 and cathepsin B,accompanied with the accumulation of LC3-II,ubiquitin and insoluble p62.Comparatively,autophagy induction elicited overt neuroprotection at 2 and 7 days after tMCAO,and this neuroprotection might be elicited by the enhancement of autophagy flux.Conclusion Our study suggests that autophagy confers neuroprotection at the subacute phase of tMCAO but has few effects on neurological outcomes after pMCAO.

Neuroprotective Potential of Cerium Oxide Nanoparticles for Focal Cerebral Ischemic Stroke

During the previous years, with the emerging of nanotechnology, the enormous capabilities of nanoparticles have drawn great attention from researchers in terms of their potentials in various aspects of pharmacology. Cerium oxide nanoparticles（nanoceria）, considered as one of the most widely used nanomaterials, due to its tempting catalytic antioxidant properties, show a promising potential in diverse disorders, such as cerebral ischemic stroke（CIS）, cancer, neurodegenerative and inflammatory diseases. Overwhelming generation of reactive oxygen species（ROS） and reactive nitrogen species（RNS） during cerebral ischemia and reperfusion periods is known to aggravate brain damage via sophisticated cellular and molecular mechanisms, and therefore exploration of the antioxidant capacities of nanoceria becomes a new approach in reducing cerebral ischemic injury. Furthermore, utilizing nanoceria as a drug carrier might display the propensity to overcome limitations or inefficacy of other conceivable neuroprotectants and exhibit synergistic effects. In this review, we emphasize on the principle features of nanoceria and current researches concerning nanoceria as a potential therapeutic agent or carrier in improving the prognosis of CIS.

Effects of Integrins and Integrin αvβ3 Inhibitor on Angiogenesis in Cerebral Ischemic Stroke

Summary： Integrins such as αvβ3, α5β31 play a key role in angiogenesis regulation, invasion and metastasis, inflammation, wound healing, etc. The up-regulation of integrin αvβ3 after cerebral ischemic stroke can promote angiogenesis, which in turn improves functional recovery. In addition, the integrin αvβ3 inhibitor can block the blood-brain barrier （BBB） leakage induced by vascular endothelial growth factor （VEGF） and also can reduce inflammatory reaction, decrease the deposition of fibrinogen. Other studies showed that integrin αvβ3 is not essential in revascularization. Therefore, the effect of integrin αvβ3 in the whole process of brain function recovery merits further study.

Electroacupuncture induces acute changes in cerebral cortical mi RNA profile, improves cerebral blood flow and alleviates neurological deficits in a rat model of stroke

Electroacupuncture has been shown to improve cerebral blood flow in animal models of stroke. However, it is unclear whether electroacupuncture alters mi RNA expression in the cortex. In this study, we examined changes in the cerebral cortical mi RNA profile, cerebral blood flow and neurological function induced by electroacupuncture in a rat model of stroke. Electroacupuncture was performed at Renzhong（GV26） and Neiguan（PC6）, with a frequency of 2 Hz, continuous wave, current intensity of 3.0 m A, and stimulation time of 1 minute. Electroacupuncture increased cerebral blood flow and alleviated neurological impairment in the rats. mi RNA microarray profiling revealed that the vascular endothelial growth factor signaling pathway, which links cell proliferation with stroke, was most significantly affected by electroacupuncture. Electroacupuncture induced changes in expression of rno-mi R-206-3p, rno-mi R-3473, rno-mi R-6216 and rno-mi R-494-3p, and these changes were confirmed by quantitative real-time polymerase chain reaction. Our findings suggest that changes in cell proliferation-associated mi RNA expression induced by electroacupuncture might be associated with the improved cerebral blood supply and functional recovery following stroke.

Middle cerebral artery occlusion methods in rat versus mouse model of transient focal cerebral ischemic stroke

Experimental stroke research commonly employs focal cerebral ischemic rat models （Bederson et al., 1986a; Longa et al., 1989）. In human patients, ischemic stroke typically results from thrombotic or embolic occlusion of a major cerebral artery, usually the mid- dle cerebral artery （MCA）. Experimental focal cerebral ischemia models have been employed to mimic human stroke （Durukan and Tatlisumak, 2007）. Rodent models of focal cerebral ischemia that do not require craniotomy have been developed using intraluminal suture occlusion of the MCA （MCA occlusion, MCAO） （Rosamond et al., 2008）. Furthermore, mouse MCAO models have been wide- ly used and extended to genetic studies of cell death or recovery mechanisms （Liu and McCullough, 2011）. Genetically engineered mouse stroke models are particularly useful for evaluation of isch- emic pathophysiology and the design of new prophylactic, neuro- protective, and therapeutic agents and interventions （Armstead et al., 2010）. During the past two decades, MCAO surgical techniques have been developed that do not reveal surgical techniques for mouse MCAO model engineering. Therefore, we compared MCAO surgical methods in rats and mice.

CLINICAL OBSERVATION ABOUT THE EFFECT OF BLOOD-LETTING OF JING-POINTS ON CEREBRAL BLOOD FLOW IN STROKE PATIENTS AT THE EARLY STAGE AND EXPERIMENTAL STUDY ON ITS MECHANISMS IN THE RABBIT

In this paper, the authors sum their research results about the effect of blood-letting of Jing (Well)-point on cerebral blood flow both in stroke patients and in experimental cerebral ischemia, cerebral hematoma and hypertension rabbits. In 30 cases of stroke (cerebral hemorrhage and cerebral infarction) patients, blood flow state of the anterior cerebral artery (ACA), middle cerebral artery (MCA) and the posterior cerebral artery (PCA), and the blood flow velocity of the bilateral vertebral artery (VA) and the basil artery (BA) are determined before and after pricking blood of the Twelve Jing-points. In experimental cerebral ischemia (by occlusion of the common carotid artery) rabbits, cerebral hematoma model rabbits and intravenous injection of noradrenaline induced hypertension rabbits, rheoencephalogram (REC) is detected before and after blood letting of the twelve "Jing"-points. In these 30 stroke patients, ultrasound Doppler examination’s results show that in 22 cases (73.33%) whose blood flow velocity decreases, after blood-letting of the 12 Jing-points, it increases significantly (P<0.01); in the rest 8 cases ( 26.67%) whose blood flow velocity speeds up, after treatment, it decreases evidently (P<0.01), showing a good dual-directional regulative effect of blood-letting therapy. In experimental cerebral ischemia rabbits, cerebral hematoma rabbits and hypertension rabbits whose REG lowers in the amplitude apparently (P<0.01), after blood letting stimulation of the 12 Jing-points, it increases at different degrees. Three patterns of stimulation as blood letting stimulation, pain stimulation and Jing-point stimulation, also the 3 factors of blood-letting therapy, may contribute to their effect on improvement of the cerebral blood flow. Somatic afferent nerve, sympathetic nerve of the vascular wall, central cholinergic nerve (M receptors) and adrenergic nerve (α receptors) participate in the effect of blood letting on cerebral blood flow.

EXPLORING THE MECHANISM OF ACUPUNCTURE IN THE TREATMENT OF STROKE FROM CHANGES OF GLUCOSE METABOLISM IN THE CEREBRAL MOTOR CENTER

Objective: To observe the effect of acupuncture on cerebral glucose metabolism in stroke patients. Methods:Changes of cerebral glucose metabolism before and after acupuncture stimulation were observed in six cases of stroke patients by using positron emission tomography (PET) scanner. Elecrocacupuncture (EA,4 Hz, continuous waves and duration of 20 min) was applied to Baihui (百会 GV 20) and right Qubin (曲鬓 GB 7). 18 Fluorine deox yglucose (18FDG), a developer (radioactive form of glucose) for showing the levels of the brain functional activity was given to the patients intravenously. SPM software was used to deal with the data of each pixel point by unilateral t-test (Ts: P = 0.05), then, the regions showing increase/decrease of the glucose metabolism were obtained. Results: After acupuncture stimulation, significant increase of glucose metabolism was found to be in the first somatic motor cortical region (Ml), supplementary motor area (SMA), premotor area (PMC), and the superior parietal lobule (LPs) on the healthy side of the brain; while the decrease of glucose metabolism found in MI, PMC and LPs on the focus side. In addition to the cerebral regions related to the motor function, changes of glucose metabolism were also found in the parietal lobule and basal ganglion area, central parietal gyrus, superior parietal gyrus, putamen, cerebellum, etc. .Conclusion: Acupuncture of Qubin (GB 7) and Baihui (GV 20) can activate motor-related cerebral structures in the bilateral cerebral hemisphere and induce excitement reaction of the potentially correlative motor area so as to compensate or assist the injured motor area to play a role in improving motor function in stroke patients.

Doppler examination and cerebral arterial stricture in patients with ischemic stroke

BACKGROUND: With the development of interventional therapy, it is necessary for evaluating cerebral vessels to instruct treatment and determine prognosis of patients with ischemic stroke; however, correlation of distribution of infarction focus and clinical symptoms with degrees of cerebrovascular stricture is still unclear. OBJECTIVE: To evaluate the characteristics of cerebral arterial stricture of patients with ischemic stroke with transcranial Doppler (TCD) and color duplex flow imaging (CDFI) and compare the correlation between distribution of cerebral infarction focus and clinical types with magnetic resonance imaging (MRI). DESIGN: Contrast observation. SETTING: Department of Neurology, the First Hospital of Jilin University. PARTICIPANTS: A total of 159 patients with ischemic stroke were selected from the Department of Neurology, the First Hospital of Jilin University from January to December 2005, including 106 males and 53 females aged from 27 to 88 years. Bases on diagnostic criteria of cerebrovascular disease established by Rao et al, clinical manifestations of all patients were evaluated with CT or nuclear magnetic resonance. All patients provided the confirmed consent. METHODS: The accepted patients received TCD and CDFI examination at 1 week after onset of ischemic stroke. Among them, 112 patients received cerebrovascular imaging examination simultaneously. MRI was used to check cerebral infarction focus and cerebrovascular stricture > 50% was regarded as the accepted vessels. In addition, DWI-T2 TCD (Germany) was used to check middle cerebral artery, and degrees of middle cerebral artery were classified into mild, moderate and severe stricture based on blood velocity (140 cm/s, 180 cm/s). Stroke was classified based on characteristics of infarction focus and clinical symptoms showed with MRI and correlation with degrees of cerebrovascular stricture was analyzed simultaneously. MAIN OUTCOME MEASURES: Correlation between the characteristics of ischemic stroke and clinical symptoms checked with TCD and CDFI. RESULTS: A total of 159 patients with ischemic stroke were involved in the final analysis; in addition, 112 cases received cerebrovascular imaging examination simultaneously. ① MRI results of 159 patients with cerebral artery occlusive disease (CAOD): There were 131 patients (82.3%) with cerebral infarction, 40 (25.2%) with transient ischemic attack and 4 (2.5%) with subclavian steal syndrome (SSS). ② Infarction types with MRI examination: There were 33 patients (20.8%) with solitary cerebral infarction and 98 (61.6%) with multiple-cerebral infarction. ③ Results of TCD, CDFI, MRI angiography, CT angiography and digital subtraction angiography (DSA): Among 112 patients, 181 lesion sites (61.8%) were located in cranium and 112 lesion sites were located out of cranium; especially, lesion site was mostly observed in stem of middle cerebral artery (31.2%) and watershed of basilar artery (7.2%) in cranium and the beginning site of internal carotid artery (21.4%) out of cranium. ④ Correlation of vascular stricture checking with TCD, MRI and clinical diagnosis: On one hand, MRI and clinical diagnosis demonstrated that 68 patients had a watershed infarction; meanwhile, TCD examination indicated that there were 3 patients with mild vascular stricture, 24 with moderate vascular stricture and 36 with severe vascular stricture. On the other hand, among 68 patients with non-watershed infarction, there were 27 patient with mild vascular stricture, 26 with moderate vascular stricture and 15 with severe vascular stricture. There were significant differences (χ2 =26.854, P =0.001). Clinical diagnosis indicated that 40 patients had transient ischemic attack and TCD examination demonstrated that there were 8 patient with mild vascular stricture, 12 with moderate vascular stricture and 20 with severe vascular stricture. There were significant differences as compared with 68 patients with watershed infarction (χ2 =21.258, P =0.001). ⑤ Correlation of vascular stricture checking with CDFI, MRI and clinical diagnosis: On one hand, among patients who were determined as watershed infarction with MRI and clinical diagnosis, CDFI examination indicated that there were 32 patients with mild vascular stricture at neck, 25 with moderate vascular stricture and 6 with severe vascular stricture. On the other hand, among patients with non-watershed infarction, there were 48 patient with mild vascular stricture, 18 with moderate vascular stricture and 2 with severe vascular stricture. There were significant differences (χ2 =6.018, P =0.019). Among patients with transient ischemic attack checking with clinical diagnosis, there were 23 patient with mild vascular stricture, 9 with moderate vascular stricture and 8 with severe vascular stricture. There were no significant differences as compared with patients with non-watershed infarction (χ2 =0.597, P =0.440). CONCLUSION: ① TCD and CDFI are effective marks to determine cerebral arterial stricture and hemodynamical changes. ② Infarction and transient ischemic attack at watershed are generally clinical phenotypes of CAOD patients and infarction at watershed is correlated with degrees of cerebrovascular stricture. ③ TCD, MRI and clinical analysis of stroke types are significant for instructing treatment and evaluate prognosis.

Concepts and opportunities for repair in cerebral microvascular disease and white matter stroke

Diffuse changes in white matter resulting from cerebral microvascular disease contribute to cognitive impairment （Jokinen et al., 2011）, declines in global functionality （Inzitari et al., 2009）, and even death （Debette and Markus, 2010）. Twenty years ago, estimations of the clinical incidence of ce- rebral microvascular disease approached 11 million per year in the US alone （Leary and Saver, 2003）. More recent estima- tions suggest the prevalence of diffuse white matter disease and silent brain infarction approaches 20% and increases dramatically in the presence of cardiovascular risk factors （Fanning et al., 2014）.

Nonhuman primate models of focal cerebral ischemia

Rodents have been widely used in the production of cerebral ischemia models. However, successful therapies have been proven on experimental rodent stroke model, and they have often failed to be effective when tested clinically. Therefore, nonhuman primates were recommended as the ideal alternatives, owing to their similarities with the human cerebrovascular system, brain metabolism, grey to white matter ratio and even their rich behavioral repertoire. The present review is a thorough summary of ten methods that establish nonhuman primate models of focal cerebral ischemia; electrocoagulation, endothelin-1-induced occlusion, microvascular clip occlusion, autologous blood clot embolization, balloon inflation, microcatheter embolization, coil embolization, surgical suture embolization, suture, and photochemical induction methods. This review addresses the advantages and disadvantages of each method, as well as precautions for each model, compared nonhuman primates with rodents, different species of nonhuman primates and different modeling methods. Finally it discusses various factors that need to be considered when modelling and the method of evaluation after modelling. These are critical for understanding their respective strengths and weaknesses and underlie the selection of the optimum model.

Inhibition of cerebral ischemia/reperfusion injuryinduced apoptosis:nicotiflorin and JAK2/STAT3 pathway

Nicotiflorin is a flavonoid extracted from Carthamus tinctorius.Previous studies have shown its cerebral protective effect,but the mechanism is undefined.In this study,we aimed to determine whether nicotiflorin protects against cerebral ischemia/reperfusion injury-induced apoptosis through the JAK2/STAT3 pathway.The cerebral ischemia/reperfusion injury model was established by middle cerebral artery occlusion/reperfusion.Nicotiflorin（10 mg/kg） was administered by tail vein injection.Cell apoptosis in the ischemic cerebral cortex was examined by hematoxylin-eosin staining and terminal deoxynucleotidyl transferase d UTP nick end labeling assay.Bcl-2 and Bax expression levels in ischemic cerebral cortex were examined by immunohistochemial staining.Additionally,p-JAK2,p-STAT3,Bcl-2,Bax,and caspase-3 levels in ischemic cerebral cortex were examined by western blot assay.Nicotiflorin altered the shape and structure of injured neurons,decreased the number of apoptotic cells,down-regulates expression of p-JAK2,p-STAT3,caspase-3,and Bax,decreased Bax immunoredactivity,and increased Bcl-2 protein expression and immunoreactivity.These results suggest that nicotiflorin protects against cerebral ischemia/reperfusion injury-induced apoptosis via the JAK2/STAT3 pathway.

Evaluation of the Curative Effect of "Xingnao Kaiqiao" Acupuncture Based on Brunnstrom Staging on Upper Limb and Hand Motor Function in the Recovery Period after Stroke

Objective: To observe the effects of Xingnao Kaiqiao acupuncture(醒脑开窍针) on the motor function of upper limb and hand in the recovery period after stroke. Methods: Seventy-six cases of hemiplegia patients with ischemic stroke were divided into the treatment group and the control group(n=38 in each). Based on the Brunnstrom's stage of Xingnao Kaiqiao acupuncture combined with rehabilitation training was used in the treatment group, and the control group was given rehabilitation training. FuglMeyer Assessment of the upper extremity(FMA-UE), Action Research Arm Test(ARAT) and Simple Test for Evaluating hand Function(STEF) were adopted separately to compare scores before treatment and 8 weeks after treatment. Results: The difference was not statistically significant in the two groups of patients for comparison of FMA-UE, ARAT and STEF scores before treatment(P>0.05). The difference was statistically significant in the two groups of score comparison of FMA-UE, ARAT and STEF after treatment(P<0.05). Conclusion: The Xingnao Kaiqiao acupuncture has its unique advantages in improving recovery of motor function of upper limb and hand in recovery period after stroke.

Gait improvement after treadmill training in ischemic stroke survivors A critical review of functional MRI studies

Stroke survivors often present with abnormal gait, movement training can improve the walking performance post-stroke, and functional MRI can objectively evaluate the brain functions before and after movement training. This paper analyzes the functional MRI changes in patients with ischemic stroke after treadmill training with voluntary and passive ankle dorsiflexion. Functional MRI showed that there are some changes in some regions of patients with ischemic stroke including primary sensorimotor cortex, supplementary motor area and cingulate motor area after treadmill training. These findings suggest that treadmill training likely improves ischemic stroke patients＇ lower limb functions and gait performance and promotes stroke recovery by changing patients＇ brain plasticity; meanwhile, the novel treadmill training methods can better training effects.

Danshen-Chuanxiongqin Injection attenuates cerebral ischemic stroke by inhibiting neuroinflammation via the TLR2/ TLR4-MyD88-NF-κB Pathway in tMCAO mice

Danshen-Chuanxiongqin Injection(DCI)is a commonly used traditional Chinese medicine for the treatment of cerebral ischemic stroke in China.However,its underlying mechanisms remain completely understood.The current study was designed to explore the protective mechanisms of DCI against cerebral ischemic stroke through integrating whole-transcriptome sequencing coupled with network pharmacology analysis.First,using a mouse model of cerebral ischemic stroke by transient middle cerebral artery occlusion(tMCAO),we found that DCI(4.10 mL·kg−1)significantly alleviated cerebral ischemic infarction,neurological deficits,and the pathological injury of hippocampal and cortical neurons in mice.Next,the whole-transcriptome sequencing was performed on brain tissues.The cerebral ischemia disease(CID)network was constructed by integrating transcriptome sequencing data and cerebrovascular disease-related genes.The results showed CID network was imbalanced due to tMCAO,but a recovery regulation was observed after DCI treatment.Pathway analysis of the key genes with recovery efficiency showed that the neuroinflammation signaling pathway was highly enriched,while the TLR2/TLR4-MyD88-NF-κB pathway was predicted to be affected.Consistently,the in vivo validation experiments confirmed that DCI exhibited protective effects against cerebral ischemic stroke by inhibiting neuroinflammation via the TLR2/TLR4-MyD88-NF-κB pathway.More interestingly,DCI markedly suppressed the neutrophils infiltrated into the brain parenchyma via the choroid plexus route and showed anti-neuroinflammation effects.In conclusion,our results provide dependable evidence that inhibiting neuroinflammation via the TLR2/TLR4-MyD88-NF-κB pathway is the main mechanism of DCI against cerebral ischemic stroke in mice.