Increased activation of the caudate nucleus and parahippocampal gyrus in Parkinson's disease patients with dysphagia after repetitive transcranial magnetic stimulation: a case-control study

Repetitive transcranial magnetic stimulation(r TMS)has been shown to effectively improve impaired swallowing in Parkinson's disease(PD)patients with dysphagia.However,little is known about how r TMS affects the corresponding brain regions in this patient group.In this casecontrol study,we examined data from 38 PD patients with dysphagia who received treatment at Beijing Rehabilitation Medicine Academy,Capital Medical University.The patients received high-frequency r TMS of the motor cortex once per day for 10 successive days.Changes in brain activation were compared via functional magnetic resonance imaging in PD patients with dysphagia and healthy controls.The results revealed that before treatment,PD patients with dysphagia showed greater activation in the precentral gyrus,supplementary motor area,and cerebellum compared with healthy controls,and this enhanced activation was weakened after treatment.Furthermore,before treatment,PD patients with dysphagia exhibited decreased activation in the parahippocampal gyrus,caudate nucleus,and left thalamus compared with healthy controls,and this activation increased after treatment.In addition,PD patients with dysphagia reported improved subjective swallowing sensations after r TMS.These findings suggest that swallowing function in PD patients with dysphagia improved after r TMS of the motor cortex.This may have been due to enhanced activation of the caudate nucleus and parahippocampal gyrus.The study protocol was approved by the Ethics Committee of Beijing Rehabilitation Hospital of Capital Medical University(approval No.2018 bkky017)on March 6,2018 and was registered with Chinese Clinical Trial Registry(registration No.Chi CTR 1800017207)on July 18,2018.     

Central swallowing in normal adults using functional magnetic resonance imaging

BACKGROUND:While brain-imaging studies in healthy adults have indicated that multiple cortical regions are involved in swallowing,these functional imaging techniques have not been extensively applied to the complete understand neurophysiology of swallowing in China.A full understanding of normal swallowing neurophysiology is important for improving functional outcomes for dysphagia due to neurologic disorders or damage with increasing age.Thus the interpretations of the functional contributions of variou...     

Functional MRI activation of primary and secondary motor areas in healthy subjects☆

BACKGROUND： Functional MRI （fMRI） demonstrates the localization of hand representation in the motor cortex, thereby providing feasible noninvasive mapping of functional activities in the human brain.
OBJECTIVE： To observe cortical activation within different cortical motor regions during repetitive hand movements in healthy subjects through the use of fMRI.
DESIGN： An observational study, with each subject acting as his own control.
SETTING： Department of Radiology, the First Affiliated Hospital of Nanchang University.
PARTICIPANTS： Seven healthy volunteers, 4 males and 3 females, aged 19 to 38 years, participated in the study. All subjects were right-handed, with no neurological or psychological disorders. Informed written consent was obtained from all subjects, and the study was approved by the Institutional Review Board of the First Affiliated Hospital of Nanchang University.
METHODS： The study was performed at the Department of Radiology between June-August 2005. A 1.5 Tesla Siemens MRI scanner （Symphony, Germany） was used to acquire T1-weighted structural images, which were oriented parallel to the line running through the anterior and the posterior commissures. Subjects were instructed on a task and were allowed to practice briefly prior to the imaging procedure. The motor activation task consisted of the right hand performing a clenching movement. The T1-W images were acquired from six alternating epochs of rest and activation from all seven healthy subjects. Data were collected with echoplanar imaging of brain oxygen level dependent （BOLD） sequence. Each series comprised six cycles of task performance （30 seconds）, alternating with rest （30 seconds） periods, and 3-second time intervals. The differences between active and baseline fMRI imaging were calculated using the student t-test. Differential maps were overlaid on the high resolution TI-W structural image for neuroanatomical correlation of activation areas.
MAIN OUTCOME MEASURES： The omega-shaped hand knob     

Evidence of cortical reorganization of language networks atfer stroke with subacute Broca’s aphasia:a blood oxygenation level dependent-functional magnetic resonance imaging study

Aphasia is an acquired language disorder that is a common consequence of stroke. hTe pathogenesis of the disease is not fully understood, and as a result, current treatment options are not satisfactory. Here, we used blood oxygenation level-dependent functional magnetic reso-nance imaging to evaluate the activation of bilateral cortices in patients with Broca’s aphasia 1 to 3 months atfer stroke. Our results showed that language expression was associated with multiple brain regions in which the right hemisphere participated in the generation of lan-guage. hTe activation areas in the letf hemisphere of aphasia patients were signiifcantly smaller compared with those in healthy adults. hTe activation frequency, volumes, and intensity in the regions related to language, such as the letf inferior frontal gyrus (Broca’s area), the letf superior temporal gyrus, and the right inferior frontal gyrus (the mirror region of Broca’s area), were lower in patients compared with healthy adults. In contrast, activation in the right superior temporal gyrus, the bilateral superior parietal lobule, and the letf inferior temporal gyrus was stronger in patients compared with healthy controls. hTese results suggest that the right inferior frontal gyrus plays a role in the recovery of language function in the subacute stage of stroke-related aphasia by increasing the engagement of related brain areas.     

Brain activation and inhibition after acupuncture at Taichong and Taixi: resting-state functional magnetic resonance imaging

Acupuncture can induce changes in the brain. However, the majority of studies to date have focused on a single acupoint at a time. In the present study, we observed activity changes in the brains of healthy volunteers before and after acupuncture at Taichong(LR3) and Taixi(KI3) using resting-state functional magnetic resonance imaging. Fifteen healthy volunteers underwent resting-state functional magnetic resonance imaging of the brain 15 minutes before acupuncture, then received acupuncture at Taichong and Taixi using the nail-pressing needle insertion method, after which the needle was retained in place for 30 minutes. Fifteen minutes after withdrawal of the needle, the volunteers underwent a further session of resting-state functional magnetic resonance imaging, which revealed that the amplitude of low-frequency fluctuation, a measure of spontaneous neuronal activity, increased mainly in the cerebral occipital lobe and middle occipital gyrus(Brodmann area 18/19), inferior occipital gyrus(Brodmann area 18) and cuneus(Brodmann area 18), but decreased mainly in the gyrus rectus of the frontal lobe(Brodmann area 11), inferior frontal gyrus(Brodmann area 44) and the center of the posterior lobe of the cerebellum. The present findings indicate that acupuncture at Taichong and Taixi specifically promote blood flow and activation in the brain areas related to vision, emotion and cognition, and inhibit brain areas related to emotion, attention, phonological and semantic processing, and memory.     

Compensatory recombination phenomena of neurological functions in central dysphagia patients

We speculate that cortical reactions evoked by swallowing activity may be abnormal in patients with central infarction with dysphagia. The present study aimed to detect functional imaging features of cerebral cortex in central dysphagia patients by using blood oxygen level-dependent functional magnetic resonance imaging techniques. The results showed that when normal controls swallowed, primary motor cortex(BA4), insula(BA13), premotor cortex(BA6/8), supramarginal gyrus(BA40), and anterior cingulate cortex(BA24/32) were activated, and that the size of the activated areas were larger in the left hemisphere compared with the right. In recurrent cerebral infarction patients with central dysphagia, BA4, BA13, BA40 and BA6/8 areas were activated, while the degree of activation in BA24/32 was decreased. Additionally, more areas were activated, including posterior cingulate cortex(BA23/31), visual association cortex(BA18/19), primary auditory cortex(BA41) and parahippocampal cortex(BA36). Somatosensory association cortex(BA7) and left cerebellum in patients with recurrent cerebral infarction with central dysphagia were also activated. Experimental findings suggest that the cerebral cortex has obvious hemisphere lateralization in response to swallowing, and patients with recurrent cerebral infarction with central dysphagia show compensatory recombination phenomena of neurological functions. In rehabilitative treatment, using the favorite food of patients can stimulate swallowing through visual, auditory, and other nerve conduction pathways, thus promoting compensatory recombination of the central cortex functions.     

Patterns of cortical reorganization in facial synkinesis:a task functional magnetic resonance imaging study

Facial synkinesis,a sequela of peripheral facial nerve palsy,is characterized by simultaneous involuntary facial movement during a voluntary desired one.Maladaptive cortical plasticity might be involved in the dysfunction of facial muscles.This cohort study investigated the cortical functional alterations in patients with unilateral facial synkinesis,using the task functional magnetic resonance imaging.Facial motor tasks,including blinking and smiling,were performed by 16 patients(aged 30.6 ± 4.5 years,14 females/2 males) and 24 age-and sex-matched healthy controls(aged 29.1 ± 4.2 years,19 females/5 males).Results demonstrated that activation in the cortico-facial motor representation area was lower during tasks in patients with facial synkinesis compared with healthy controls.Facial movements on either side performed by patients caused more intensive activation of the supplementary motor area on the contralateral side of the affected face,than those on the unaffected side.Our results revealed that there was cortical reorganization in the primary sensorimotor area and the supplementary motor area.This study was registered in Chinese Clinical Trial Registry(registration number: Chi CTR1800014630).     

Longitudial observation of dynamic changes in cortical function and white matter fibrous structure of patients with visual pathway lesions by blood oxygenation level dependent-functional magnetic resonance imaging combined with diffusion tensor imaging

BACKGROUND: Functional magnetic resonance imaging (fMRI) is initially used for visual cortex location. However, the application of fMRI in investigating the development of visual pathway lesions needs to be further observed. OBJECTIVE: This study is to longitudially observe the dynamic changes in cortical function and white matter fibrous structure of patients with visual pathway lesions by blood oxygenation level dependent-functional magnetic resonance imaging (BOLD-fMRI) combined with diffusion tensor imaging (DTI), and to analyze the characteristics of brain function and structural recombination at convalescent period of lesions. DESIGN: Randomized controlled observation. SETTING: Department of Radiology, the General Hospital of Nanjing Military Area Command of Chinese PLA. PARTICIPANTS: Eight patients with unilateral or bilateral visual disorder caused by visual pathway lesions, who admitted to Department of Radiology, the General Hospital of Nanjing Military Area Command of Chinese PLA from January to September 2006 were involved, and served as experimental subjects. The patients, 6 males and 2 females, were aged 16–67 years. They had visual disorder confirmed by clinical examination, i.e. visual pathway lesion, which was further diagnosed by MR or CT. Another 12 subjects generally matching to those patients of experimental group in gender, age and sight, who received health examination in synchronization were involved and served as controls. The subjects had no history of eye diseases. Their binocular visual acuity (or corrected visual acuity) was over 1.0. Both routine examination of ophthalmology and examination of fundus were normal. Informed consents of detected items were obtained from all the subjects. METHODS: Signa Excite HD 1.5T magnetic resonance imaging system with 16 passages (GE Company, USA) and coil with 8 passages were used; brain functional stimulus apparatus (SAV-8800. Meide Company) was used for showing experimental mission. At the early stage and convalescent period of lesions, the patients with visual pathway lesion were examined by BOLD-fMRI combined with DTI, respectively, and brain activation volume, optic radiation anatomical structure and fractional anisotropy (FA) value were compared before and after symptomatic treatment under the stimulation to both eyes. The above-mentioned indexes were observed and compared between experimental and control groups. MAIN OUTCOME MEASURES: BOLD-fMRI and DTI manifestations before and after treatment in the experimental group and control group. RESULTS: All the 8 patients and 12 healthy subjects participated in the final analysis. ①BOLD-fMRI manifestation: Bilateral occipital lobes and calcarine gyri of control subjects were obviously activated. The activation volume of striate cortex under the stimulation to two eyes was obviously reduced in the experimental subjects than in the control subjects (P < 0.05). After treatment, the amount of activated pixel in the stimulated cortex was increased, and the activation area was expanded. ② DTI results: Bilateral optic radiation of healthy controls could be traced in the subcortex. Complete optic radiation of patients with visual pathway lesion could be shown. There was no significant difference in optic radiation between experimental subjects and healthy controls. No significant difference in optic radiation was found before and after observation, either (P > 0.05). In 4 patients with occipital lobe and optical center lesions, optic radial fiber was partially interrupted and tenuous, displacement could be found, and FA value was obviously decreased; After treatment, optic radial fiber bundle recovered to some extent, and FA value was also increased. CONCLUSION: BOLD-fMRI and DTI explain the development of lesion from the aspect of cortical function and fibrous anatomy. It has important significance for investigating the recombination of cortical function area following visual pathway lesion.     

精神分裂症患者记忆围棋子位置时的脑激活区域

BACKGROUND： Go, a traditional Chinese chess-like game, requires many unknown functions of the brain including attention, imaging, problem solving and processing of spatial working memory. To date, it remains uncertain whether the intellectual activities required to play Go are related to the frontal lobe. OBJECTIVE： To investigate various patterns of brain region activity while schizophrenic patients and normal subjects engaged in memorizing piece placement in the Chinese game of Go. Spatial working memory was measured in order to validate whether the prefrontal lobe participates in this memory process.
DESIGN, TIME AND SETTING： Non-randomized, concurrent control trial was performed at Second Xiangya Hospital of Central South University, between May and December 2004.
PARTICIPANTS： A total of nine Chinese schizophrenic patients with no brain or bodily diseases and not undergoing electroshock treatment, who were in accordance with the DSM-Ⅳ criteria for schizophrenia, as well as thirteen healthy staffs and students with matched age, sex, and education were included. Patients and control subjects had no neurological disorders or mental retardation. In addition, all participants were right-handed. METHODS： The cognitive task for functional magnetic resonance imaging was a block design experiment. Both groups were asked to remember the placement of pieces in the Chinese game of Go on a computer screen. A brain activation map was analyzed in SPM99.
MAIN OUTCOME MEASURES： Brain responses were compared with regard to activation region size, volume, and asymmetry indices. RESULTS： Compared with the control group, the reaction time was significantly delayed in schizophrenics performing the working memory task （P 〈 0.05）. When performing the tasks, normal subjects showed significant activation of the bilateral dorsolateral prefrontal lobe with left dominance; the asymmetry indices were： frontal lobe, ＋0.32; temporal lobe, 0.58; parietal lobe, 0.41 ; and occipital lobe, 0.34. On the other hand, schizophrenics showed right dominance and had a broader activation region of the prefrontal lobe （asymmetry indices： frontal lobe, 0.10; temporal lobe, ＋0.38; parietal lobe, ＋0.24; and occipital lobe, 0.00）. When comparing the normal group subtracted with the schizophrenic group, no significant lateralization was found in the frontal lobes but significant activation was found in the left anterior central gyrus, left middle frontal gyrus and in both sides of the cingulate gyrus. Comparing the schizophrenic group subtracted with the normal group, there was significant right lateralization of the frontal lobe and abnormally activated regions on both sides of the anterior central gyrus, middle frontal gyrus, left inferior frontal gyrus, right medial frontal gyrus and the right insular lobe. CONCLUSION： Different brain activation regions are involved in memorizing the placement of pieces in Chinese Go between schizophrenia and healthy subjects. Schizophrenics showed right dominance and border activation range, indicating that the prefrontal cortex plays an important role in memory information processing and resource allocation when remembering piece placement in the game of Go.     

Morphological changes in gray matter volume correlate with catechol-O-methyl transferase gene Val158Met polymorphism in first-episode treatment-nave patients with schizophrenia

The catechol-O-methyltransferase(COMT) gene is a schizophrenia susceptibility gene. A common functional polymorphism of this gene,Val158/158 Met,has been proposed to influence gray matter volume(GMV). However,the effects of this polymorphism on cortical thickness/surface area in schizophrenic patients are less clear. In this study,we explored the relationship between the Val158 Met polymorphism of the COMT gene and the GMV/ cortical thickness/cortical surface area in 150 firstepisode treatment-nave patients with schizophrenia and 100 healthy controls. Main effects of diagnosis were found for GMV in the cerebellum and the visual,medial temporal,parietal,and middle frontal cortex. Patients with schizophrenia showed reduced GMVs in these regions. And main effects of genotype were detected for GMV in the left superior frontal gyrus. Moreover,a diagnosis × genotype interaction was found for the GMV of the left precuneus,and the effect of the COMT gene on GMV was due mainly to cortical thickness rather than cortical surface area. In addition,a pattern ofincreased GMV in the precuneus with increasing Met dose found in healthy controls was lost in patients with schizophrenia. These findings suggest that the COMTMet variant is associated with the disruption of dopaminergic influence on gray matter in schizophrenia,and the effect of the COMT gene on GMV in schizophrenia is mainly due to changes in cortical thickness rather than in cortical surface area.     

Environmental factors in the development and progression of late-onset Alzheimer＇s disease

Late-onset Alzheimer＇s disease （LOAD） is an age-related neurodegenerative disorder characterized by gradual loss of synapses and neurons, but its pathogenesis remains to be clarified. Neurons live in an environment constituted by neurons themselves and glial cells. In this review, we propose that the neuronal degeneration in the AD brain is partially caused by diverse environmental factors. We first discuss various environmental stresses and the corresponding responses at different levels. Then we propose some mechanisms underlying the specific pathological changes, in particular, hypothalamic-pituitary adrenal axis dysfunction at the systemic level; cerebrovascular dysfunction, metal toxicity, glial activation, and Aβ toxicity at the intercellular level; and kinase-phosphatase imbalance and epigenetic modification at the intracellular level. Finally, we discuss the possibility of developing new strategies for the prevention and treatment of LOAD from the perspective of environmental stress. We conclude that environmental factors play a significant role in the development of LOAD through multiple pathological mechanisms.     

Advances in longitudinal studies of amnestic mild cognitive impairment and Alzheimer＇s disease based on multi-modal MRI techniques

Amnestic mild cognitive impairment （aMCI） is a prodromal stage of Alzheimer＇s disease （AD）, and 75%-80% of aMCI patients finally develop AD. So, early identification of patients with aMCI or AD is of great significance for prevention and intervention. According to cross-sectional studies, it is known that the hippocampus, posterior cingulate cortex, and corpus callosum are key areas in studies based on structural MRI （sMRI）, functional MRI （fMRI）, and diffusion tensor imaging （DTI） respectively. Recently, longitudinal studies using each MRI modality have demonstrated that the neuroimaging abnormalities generally involve the posterior brain regions at the very beginning and then gradually affect the anterior areas during the progression of aMCI to AD. However, it is not known whether follow-up studies based on multi-modal neuroimaging techniques （e.g., sMRI, fMRI, and DTI） can help build effective MRI models that can be directly applied to the screening and diagnosis of aMCI and AD. Thus, in the future, large-scale multi-center follow-up studies are urgently needed, not only to build an MRI diagnostic model that can be used on a single person, but also to evaluate the variability and stability of the model in the general population. In this review, we present longitudinal studies using each MRI modality separately, and then discuss the future directions in this field.     

使用1H-MRS和LCModel对鼻喷中枢性镇痛药后脑代谢物谷氨酸复合物的

BACKGROUND： In localized brain proton magnetic resonance spectroscopy （^1H-MRS）, metabolite levels are often expressed as ratios, rather than absolute concentrations. Frequently, the denominator is creatine, which is assumed to be stable in normal, as well as many pathological, states. However, in vivo creatine levels do not remain constant. Therefore, absolute metabolite measurements, which provide the precise concentrations of certain chemical compounds, are superior to metabolite ratios for determining pathological and evolutional changes.
OBJECTIVE： To investigate the feasibility of quantification analysis of brain metabolite changes caused by central analgesics nasal spray using the ^1H-MRS and linear combination model （LCModel） methods.
DESIGN, TIME AND SETTING： This neuroimaging, observational, animal study was performed at the Laboratory of the Department of Medical Imaging, Second Affiliated Hospital, Medical College, Shantou University, China from July to December 2007.
MATERIALS： Butorphanol tartrate nasal spray, as a mixed agonist-antagonist opioid analgesic, was purchased from Shanghai Hengrui Pharmacy, China. A General Electric Signa 1.5T System （General Electric Medical Systems, Milwaukee, WI, USA） and LCModel software （Stephen Provencher, Oakville, Ontario, Canada） were used in this study.
METHODS： MRS images were acquired in ten healthy swine aged 2 weeks using single-voxel point-resolved spectroscopic sequence. A region of interest （2 cm × 2 cm × 2 cm） was placed in the image centers of maximum brain parenchyma. Repeated MRS scanning was performed 15-20 minutes after intranasal administration of 1 mg of butorphanol tartrate. Three settings of repetition time/echo time were selected before and after nasal spray administration 3 000 ms/30 ms,1 500 ms/30 ms, and 3 000 ms/50 ms. Metabolite concentrations were estimated by LCModel software.
MAIN OUTCOME MEASURES： ^1H-MRS spectra was obtained using various repetition time/echo time settings. Concentrations of glutamate compounds （glutamate ＋ glutamine）, N-acetyl aspartate, and choline were detected in swine brain prior to and following nasal spray treatment. RESULTS： The glutamate compounds curve was consistent with original spectra, when a repetition time/echo time of 3 000 ms/30 ms was adopted. Concentrations of glutamate compounds, N-acetyl aspartate, and choline decreased following administration. The most significant reduction was observed in glutamate compound concentrations from （9.28 ± 0.54） mmol/kg to （7.28 ± 0.54） mmol/kg （P 〈 0.05）.
CONCLUSION： ^1H-MRS and LCModel software were effectively utilized to quantitatively analyze and measure brain metabolites. Glutamate compounds might be an important neurotransmitter in central analgesia.     

高血压脑出血的显微外科治疗进展

高血压脑出血（Hypertensive intrac-rebral hemorrhage,HICH）是具有高发病率、高病死率、高致残率的急性脑血管疾病,占所有脑卒中患者的10%-20%,早期病死率可高达49.4%。随着人口老龄化,其发病率逐年提高;而外科手术的干预,使其病死率有所下降,但致残率居高不下。如何提高手术疗效和患者生存质量,一直是神经外科医师努力的方向。微侵袭血肿清除术因其手术创伤小,恢复快,是目前国内治疗高血压脑出血的重要手段。     

神经内镜联合亚低温治疗高血压基底节区脑出血

目的 探讨神经内镜联合亚低温在治疗高血压基底节区脑出血中的临床应用价值.方法 回顾性分析我院神经内镜治疗高血压基底节区脑出血患者40例的临床资料,并对治疗结果进行分析.结果 神经内镜治疗组22例(甲组),神经内镜联合亚低温治疗组18例(乙组),术后3个月根据GCS评分,甲组恢复良好1例,中残4例,重残6例,植物生存6例,死亡5例;乙组恢复良好4例,中残8例,重残3例,植物生存1例,死亡2例,两组比较差异有统计学意义(P＜0.05).两组颅内压比较第1天两者差异不明显,但第2、3天亚低温组颅内压明显降低.结论 神经内镜是治疗高血压基底节区脑出血较为有效的手术方式,联合亚低温治疗能有效降低颅内压,改善术后神经功能恢复,具有较好的临床应用价值.     

血管内皮细胞生长因子在抑郁症中作用的研究进展

抑郁症是一种发生率和致死率高、易复发的慢性精神疾病,是一种高度遗传异质性疾病,目前具体机制尚不明确。多种因素、信号途径参与了该疾病的病理生理过程,近来多项研究显示血管内皮细胞生长因子（VEGF）参与了抑郁症的病理过程,本文就VEGF在抑郁症中作用的研究进行综述性分析。     

Medial reorganization of motor function in corona radiata following middle cerebral artery infarction A case report

Peri-lesional reorganization is one of the motor recovery mechanisms following stroke. A 23-year-old female who presented with complete paralysis of the right extremities at the onset of infarct in the left middle cerebral artery territory was included. She slowly recovered some function, and could extend the affected knee with resistance after 9 months. Diffusion tensor tractography, functional MRI, and transcranial magnetic stimulation testing were performed at 7 years after onset. Results showed that diffusion tensor tractography of the affected （left） hemisphere passed through the medial corona radiata at, or around, the wall of the lateral ventricle. The contralateral primary sensorimotor cortex was activated during affected knee movements. The motor-evoked potential, which was obtained from the affected leg, exhibited corticospinal tract characteristics. Results indicated that motor function of the affected leg recovered via the corticospinal tract, which descended through the corona radiata medial to the infarct. The motor function of the affected leg was reorganized to the medial corona radiata following infarct to the middle cerebral artery territory.     

Total saponins of Panax ginseng effects on proliferation and differentiation of human embryonic neural stem cells and in a Parkinson’s disease mouse model

BACKGROUND： Total saponins of Panax ginseng （TSPG） exhibits neuroprotection against Parkinson＇s disease in the substantia nigra. OBJECTIVE： To investigate the effects of TSPG on human embryonic neural stem cells （NSCs） proliferation and differentiation into dopaminergic neurons using in vitro studies, and to observe NSC differentiation in a mouse model of Parkinson＇s disease, as well as behavioral changes before and after transplantation. DESIGN, TIME AND SETTING： In vitro neural cell biology trial and in vivo randomized, controlled animal trial were performed at the Institute of Basic Medical Sciences, Chongqing Medical University between September 2004 and December 2007. MATERIALS： TSPG （purity 〉 95%） was isolated, extracted, and identified by Chongqing Academy of Chinese Materia Medica. Recombinant human basic fibroblast growth factor （bFGF） and recombinant human epidermal growth factor （EGF） were purchased from PeproTech, USA. A total of 25 C57/BL6J mice, aged 18-20 weeks were included. Twenty were used to establish a Parkinson＇s disease model with i.p. injection of MPTP （1-methyl-4-phenyl-1, 2, 3, 6-tetrahydropyridine） and TSPG alone or combined with interleukin-1 （IL-1）-treated NSCs prior to transplantation into the corpus striatum. The remaining five mice were pretreated for 3 days with TSPG prior to MPTP injection, serving as the TSPG prevention group. METHODS： Primary NSCs were isolated, cultured and purified from embryonic cerebral cortex. Immunocytochemistry was employed to detect specific antigen expression in the NSCs. In vitro experiment： （1） to induce proliferation, NSCs were treated with TSPG, EGF＋bFGF, or TSPG＋EGF＋bFGF, respectively; （2） to induce dopaminergic neuronal differentiation, NSCs were treated with TSPG, IL-1, or TSPG＋IL-1, respectively. MAIN OUTCOME MEASURES： In vitro experiment： the effects of TSPG on NSCs proliferation were evaluated with flow cytometry and MTT assay. Tyrosine hydroxylase expression was determined by immunocytochemistry assay to observe effects of TSPG on dopaminergic neuronal differentiation. In vivo experiment： differentiation of grafted NSCs in the mouse brain was determined by immunohistochemical staining. Behavioral changes were evaluated by spontaneous activity frequency, memory function, and score of paralysis agitans. RESULTS： （1） NSCs were cultured and passaged for more than three passages. Immunocytochemistry revealed positive nestin staining, as well as neurofilament protein and glial fibrillary acidic protein. （2） TSPG significantly increased NSC proliferation, in particular when combined with EGF and bFGF, which was twice as effective as FGF or bFGF alone. TSPG also induced dopaminergic differentiation in NSCs, in particular when TSPG was added together with IL-1, resulting in an effect five times greater than that of IL-1 alone. （3） At day 30 following transplantation, most NSCs in the TSPG prevention group differentiated into dopaminergic neurons, and the scores of paralysis agitans, spontaneous activity, and memory function were significantly increased compared with TSPG alone or TSPG＋IL-1 groups （P 〈 0.05）. CONCLUSION： TSPG stimulated NSC proliferation, in particular when combined with FGF and bFGF. TSPG significantly induced dopaminergic neuronal differentiation of NSCs, and the effect was greater when combined with IL-1. In addition, TSPG greatly improved behavior in the Parkinson＇s disease mouse model following NSC transplantation. Following NSC transplantation, TSPG pretreatment exhibited superior efficacy over either TSPG alone or TSPG in combination with IL-1, in terms of behavioral improvements in the Parkinson＇s disease mouse model.     

针刺健康人足三里穴脑功能成像研究初步分析

目的采用磁共振脑功能成像（fMRI）技术观察针刺足三里穴引起脑内功能区的变化,并与近年来相关的研究结果比较,分析研究存在差异的原因。方法15例健康志愿者,采用改良组块设计方案,针刺左侧足三里穴进行fMRI扫描,实验数据采用AFNI软件分析处理,采用Monte Carlo模拟阈值校正方法（P〈0.05,α〈0.05）确定脑功能激活区。结果针刺左侧足三里穴引起双侧海马旁回、额中回、扣带回前部、右侧颞叶、海马、杏仁核、左侧额下回、右侧小脑及脑桥区域信号减弱,右侧中央前回及右侧顶下小叶区域信号增高。结论针刺正常人左侧足三里穴主要引起颞叶和边缘系统的脑功能变化,并且以信号减弱为主。与其他类似研究的结果有较明显的差异,这种差异可能与多种因素有关,有待进一步深入研究分析。