Modified constraint-induced movement therapy enhances cortical plasticity in a rat model of traumatic brain injury:a resting-state functional MRI study

Modified constraint-induced movement therapy(mCIMT)has shown beneficial effects on motor function improvement after brain injury,but the exact mechanism remains unclear.In this study,amplitude of low frequency fluctuation(ALFF)metrics measured by resting-state functional magnetic resonance imaging was obtained to investigate the efficacy and mechanism of mCIMT in a control co rtical impact(CCI)rat model simulating traumatic brain injury.At 3 days after control co rtical impact model establishment,we found that the mean ALFF(mALFF)signals were decreased in the left motor cortex,somatosensory co rtex,insula cortex and the right motor co rtex,and were increased in the right corpus callosum.After 3 weeks of an 8-hour daily mClMT treatment,the mALFF values were significantly increased in the bilateral hemispheres compared with those at 3 days postoperatively.The mALFF signal valu es of left corpus callosum,left somatosensory cortex,right medial prefro ntal cortex,right motor co rtex,left postero dorsal hippocampus,left motor cortex,right corpus callosum,and right somatosensory cortex were increased in the mCIMT group compared with the control cortical impact group.Finally,we identified brain regions with significantly decreased mALFF valu es at 3 days postoperatively.Pearson correlation coefficients with the right forelimb sliding score indicated that the improvement in motor function of the affected upper limb was associated with an increase in mALFF values in these brain regions.Our findings suggest that functional co rtical plasticity changes after brain injury,and that mCIMT is an effective method to improve affected upper limb motor function by promoting bilateral hemispheric co rtical remodeling.mALFF values correlate with behavio ral changes and can potentially be used as biomarkers to assess dynamic cortical plasticity after traumatic brain injury.

Altered protein markers related to neural plasticity and motor function following electro-acupuncture treatment in a rat model of ischemic-hypoxic brain injury

BACKGROUND：Previous studies have demonstrated that acupuncture treatment could ameliorate impaired motor function,and these positive effects might be due to neural plasticity.OBJECTIVE：Myelin basic protein（MBP）,microtubule-associated protein 2（MAP2）,growth-associated protein-43（GAP-43）,and synaptophysin（SYN） were selected as markers of neural remodeling,and expression of these markers was evaluated with regard to altered motor function following brain injury and acupuncture treatment.DESIGN,TIME AND SETTING：A completely randomized experiment was performed at the Central Laboratory of Peking University First Hospital from November 2006 to May 2007.MATERIALS：Twenty-four Sprague Dawley rat pups,aged 7 days,were selected for the present experiment.The left common carotid artery was ligated to establish a rat model of ischemic-hypoxic brain injury.METHODS：All animals were randomly divided into three groups：sham operation,model,and electro-acupuncture treatment,with 8 rats in each group.Rats in the model and electro-acupuncture treatment group underwent establishment of ischemic-hypoxic brain injury.Upon model established,rats underwent hypobaric oxygen intervention for 24 hours.Only the left common carotid artery was exposed in rats of the sham operation group,without model establishment or oxygen intervention.The rats in the electro-acupuncture treatment group were treated with electro-acupuncture.One acupuncture needle electrode was inserted into the subcutaneous layer at the Baihui and Dazhui acupoint.The stimulation condition of the electro-acupuncture simulator was set to an amplitude-modulated wave of 0-100% and alternative frequency of 100 cycles/second,as well as frequency-modulated wave of 2-100 Hz and an alternative frequency of 3 cycles/second.Maximal current through the two electrodes was limited to 3-5 mA.The stimulation lasted for 30 minutes per day for 2 weeks.Rats in the sham operation and model groups were not treated with electro-acupuncture,but only fixed to the table for the same time period.MAIN OUTCOME MEASURES：After 2 weeks stimulation,expression of MBP,MAP2,GAP-43,and SYN were detected in the brain by immunohistochemistry.Motor function was evaluated in the three groups.RESULTS：In the sham operation group,MBP was abundant in the myelinated nerve fibers.In the electro-acupuncture treatment group,however,the corpus callosum exhibited more MBP staining than the model group.MAP2 expression was increased in the model group,and increased further in the electro-acupuncture treatment group compared with the sham operation group.GAP-43 expression in the cerebral cortex was less in model group than in sham operation,but present in abundance in the electro-acupuncture treatment group.SYN expression in the cerebral cortex was less in the model and electro-acupuncture treatment group compared with the sham operation group.There was no significant difference in SYN expression and distribution between the model and electro-acupuncture treatment groups.Motor function of rats in the electro-acupuncture treatment group was significantly better than the model group（P 〈 0.05）,although function remained lower than the sham operation group（P 〈 0.05）.CONCLUSION：Two weeks of electro-acupuncture treatment improved motor function in rats,and protein markers related to neural plasticity also changed,which may be a mechanism for improved motor function in rats with ischemic-hypoxic brain injury.

Non-concomitant cortical structural and functional alterations in sensorimotor areas following incomplete spinal cord injury

Brain plasticity, including anatomical changes and functional reorganization, is the physiological basis of functional recovery after spinal cord injury（SCI）. The correlation between brain anatomical changes and functional reorganization after SCI is unclear. This study aimed to explore whether alterations of cortical structure and network function are concomitant in sensorimotor areas after incomplete SCI. Eighteen patients with incomplete SCI（mean age 40.94 ± 14.10 years old; male：female, 7：11） and 18 healthy subjects（37.33 ± 11.79 years old; male：female, 7：11） were studied by resting state functional magnetic resonance imaging. Gray matter volume（GMV） and functional connectivity were used to evaluate cortical structure and network function, respectively. There was no significant alteration of GMV in sensorimotor areas in patients with incomplete SCI compared with healthy subjects. Intra-hemispheric functional connectivity between left primary somatosensory cortex（BA1） and left primary motor cortex（BA4）, and left BA1 and left somatosensory association cortex（BA5） was decreased, as well as inter-hemispheric functional connectivity between left BA1 and right BA4, left BA1 and right BA5, and left BA4 and right BA5 in patients with SCI. Functional connectivity between both BA4 areas was also decreased. The decreased functional connectivity between the left BA1 and the right BA4 positively correlated with American Spinal Injury Association sensory score in SCI patients. The results indicate that alterations of cortical anatomical structure and network functional connectivity in sensorimotor areas were non-concomitant in patients with incomplete SCI, indicating the network functional changes in sensorimotor areas may not be dependent on anatomic structure. The strength of functional connectivity within sensorimotor areas could serve as a potential imaging biomarker for assessment and prediction of sensory function in patients with incomplete SCI. This trial was registered with the Chinese Clinical Trial Registry（registration number： Chi CTR-ROC-17013566）.

Remodeling dendritic spines for treatment of traumatic brain injury

Traumatic brain injury is an important global public health problem.Traumatic brain injury not only causes neural cell death,but also induces dendritic spine degeneration.Spared neurons from cell death in the injured brain may exhibit dendrite damage,dendritic spine degeneration,mature spine loss,synapse loss,and impairment of activity.Dendritic degeneration and synapse loss may significantly contribute to functional impairments and neurological disorders following traumatic brain injury.Normal function of the nervous system depends on maintenance of the functionally intact synaptic connections between the presynaptic and postsynaptic spines from neurons and their target cells.During synaptic plasticity,the numbers and shapes of dendritic spines undergo dynamic reorganization.Enlargement of spine heads and the formation and stabilization of new spines are associated with long-term potentiation,while spine shrinkage and retraction are associated with long-term depression.Consolidation of memory is associated with remodeling and growth of preexisting synapses and the formation of new synapses.To date,there is no effective treatment to prevent dendritic degeneration and synapse loss.This review outlines the current data related to treatments targeting dendritic spines that propose to enhance spine remodeling and improve functional recovery after traumatic brain injury.The mechanisms underlying proposed beneficial effects of therapy targeting dendritic spines remain elusive,possibly including blocking activation of Cofilin induced by beta amyloid,Ras activation,and inhibition of GSK-3 signaling pathway.Further understanding of the molecular and cellular mechanisms underlying synaptic degeneration/loss following traumatic brain injury will advance the understanding of the pathophysiology induced by traumatic brain injury and may lead to the development of novel treatments for traumatic brain injury.

中枢神经系统（CNS）损伤后功能恢复的理论（二）

上一节介绍了ＣＮＳ损伤后功能恢复的理论和促进因素以及脑可塑性理论的发展与概念。本节将讨论脑可塑性理论的形态和生理学依据及其在人和动物身上的证明。并且依据Ｌｕｒｉａ的功能重组理论，用图说明了影响脑可塑性的内、外因素。

中枢神经系统（CNS）损伤后功能恢复的理论（三）

此部分介绍了ＣＮＳ损伤的自由基理论及自由基损伤的防治。并介绍了急性损伤阶段有利于功能恢复的部分因素。

Perilesional reorganization of somatosensory function following traumatic cortical contusion A case report

The present study reports on a 23-year-old male patient with somatosensory dysfunction of the left hand following cortical contusion. His somatosensory dysfunction recovered to a nearly normal state at 6 months after injury. Functional MRI results demonstrated that the contralateral primary sensorimotor cortex centered on the primary somatosensroy cortex was activated during touch stimulation of the patient＇s right hand and either hand of control subjects. By contrast, the anterior area of the lesion centered on the precentral knob in the right hemisphere was activated during touch stimulation of the left hand. These findings show that the somatosensory function of the affected hand appears to have been recovered by the somatosensory cortex reorganizing into the anterior area of the contused primary somatosensory cortex.

Perilesional reorganization of motor function in stroke patients

Perilesional reorganization is an important recovery mechanism for stroke patients because it yields good motor outcomes. However, perilesional reorganization remains poorly understood. The scientific basis for stroke rehabilitation can be established when detailed mechanisms of recovery are clarified. In addition, studies at the subcortical level remain in the early stages. Therefore, the present study suggested that additional investigations should focus on perilesional reorganization at the subcortical level, identifying the critical period for this mechanism and determining treatment strategies and modalities to facilitate development. The present study reviews literature focused on perilesional reorganization in stroke patients with regard to demonstration, clinical characteristics, and rehabilitative aspects, as well as previous studies of perilesional reorganization at cortical and subcortical levels.

Brain remodeling after chronic median nerve compression in a rat model

Carpal tunnel syndrome is the most common compressive neuropathy,presenting with sensorimotor dysfunction.In carpal tunnel syndrome patients,irregular afferent signals on functional magnetic resonance imaging are associated with changes in neural plasticity during peripheral nerve injury.However,it is difficult to obtain multi-point neuroimaging data of the brain in the clinic.In the present study,a rat model of median nerve compression was established by median nerve ligation,i.e.,carpal tunnel syndrome model.Sensory cortex remodeling was determined by functional magnetic resonance imaging between normal rats and carpal tunnel syndrome models at 2 weeks and 2 months after operation.Stimulation of bilateral paws by electricity for 30 seconds,alternating with 30 seconds of rest period（repeatedly 3 times）,resulted in activation of the contralateral sensorimotor cortex in normal rats.When carpal tunnel syndrome rats received this stimulation,the contralateral cerebral hemisphere was markedly activated at 2 weeks after operation,including the primary motor cortex,cerebellum,and thalamus.Moreover,this activation was not visible at 2 months after operation.These findings suggest that significant remodeling of the cerebral cortex appears at 2 weeks and 2 months after median nerve compression.

Virtual reality training improves balance function

Virtual reality is a new technology that simulates a three-dimensional virtual world on a com- puter and enables the generation of visual, audio, and haptic feedback for the full immersion of users. Users can interact with and observe objects in three-dimensional visual space without limitation. At present, virtual reality training has been widely used in rehabilitation therapy for balance dysfunction. This paper summarizes related articles and other articles suggesting that virtual reality training can improve balance dysfunction in patients after neurological diseases. When patients perform virtual reality training, the prefrontal, parietal cortical areas and other motor cortical networks are activated. These activations may be involved in the reconstruction of neurons in the cerebral cortex. Growing evidence from clinical studies reveals that virtual reality training improves the neurological function of patients with spinal cord injury, cerebral palsy and other neurological impairments. These findings suggest that virtual reality training can acti- vate the cerebral cortex and improve the spatial orientation capacity of patients, thus facilitating the cortex to control balance and increase motion function.

脑损伤后功能恢复机制的研究进展

随着各种原因所致的脑损伤发病率的上升,脑损伤后的功能恢复已成为多学科研究关注的焦点。本文以脑的可塑性学说为基础,从神经细胞的改变、功能重组、功能替代、大脑皮层兴奋性改变和特殊技巧学习等几个方面,对脑损伤后的功能恢复机制进行阐述。

Effects of different frequencies of repetitive transcranial magnetic stimulation on the recovery of upper limb motor dysfunction in patients with subacute cerebral infarction

Studies have confirmed that low-frequency repetitive transcranial magnetic stimulation can decrease the activity of cortical neurons, and high-frequency repetitive transcranial magnetic stimulation can increase the excitability of cortical neurons. However, there are few studies concerning the use of different frequencies of repetitive transcranial magnetic stimulation on the recovery of upper-limb motor function after cerebral infarction. We hypothesized that different frequencies of repetitive transcranial magnetic stimulation in patients with cerebral infarction would produce different effects on the recovery of upper-limb motor function. This study enrolled 127 patients with upper-limb dysfunction during the subacute phase of cerebral infarction. These patients were randomly assigned to three groups. The low-frequency group comprised 42 patients who were treated with 1 Hz repetitive transcranial magnetic stimulation on the contralateral hemisphere primary motor cortex （M1）. The high-frequency group comprised 43 patients who were treated with 10 Hz repetitive transcranial magnetic stimulation on ipsilateral M1. Finally, the sham group comprised 42 patients who were treated with 10 Hz of false stimulation on ipsilateral M1. A total of 135 seconds of stimulation was applied in the sham group and high-frequency group. At 2 weeks after treatment, cortical latency of motor-evoked potentials and central motor conduction time were significantly lower compared with before treatment. Moreover, motor function scores were significantly improved. The above indices for the low- and high-frequency groups were significantly different compared with the sham group. However, there was no significant difference between the low- and high-frequency groups. The results show that low- and high-frequency repetitive transcranial magnetic stimulation can similarly improve upper-limb motor function in patients with cerebral infarction.

Prospects for intelligent rehabilitation techniques to treat motor dysfunction

More than half of stroke patients live with different levels of motor dysfunction after receiving routine rehabilitation treatments.Therefore,new rehabilitation technologies are urgently needed as auxiliary treatments for motor rehabilitation.Based on routine rehabilitation treatments,a new intelligent rehabilitation platform has been developed for accurate evaluation of function and rehabilitation training.The emerging intelligent rehabilitation techniques can promote the development of motor function rehabilitation in terms of informatization,standardization,and intelligence.Traditional assessment methods are mostly subjective,depending on the experience and expertise of clinicians,and lack standardization and precision.It is therefore difficult to track functional changes during the rehabilitation process.Emerging intelligent rehabilitation techniques provide objective and accurate functional assessment for stroke patients that can promote improvement of clinical guidance for treatment.Artificial intelligence and neural networks play a critical role in intelligent rehabilitation.Multiple novel techniques,such as braincomputer interfaces,virtual reality,neural circuit-magnetic stimulation,and robot-assisted therapy,have been widely used in the clinic.This review summarizes the emerging intelligent rehabilitation techniques for the evaluation and treatment of motor dysfunction caused by nervous system diseases.

盲针法电针治疗中风的前瞻性临床对照研究

目的 :应用盲针技术 ,用单盲法研究电针对中风后偏瘫的疗效 ,并探讨其可能的作用机制。方法 :6 4例急性期中风病人随机分为治疗组和对照组 ,治疗组以常规电针治疗 ,对照组予以盲针通电治疗。在治疗前、治疗第 10天和第 2 0天行NIHSS、Fugl-Meyer和Barthel指数评分。在治疗前和治疗第 2 0天行SPECT -rCBF脑显像检查 ,记录各脑区脑血流灌注 (rCBF)情况。结果 :治疗后治疗组较对照组运动功能及日常生活指数均有提高 (P <0 .0 5 ) ,且治疗组较对照组双侧额叶皮质运动区rCBF明显增加 (P <0 .0 5 )。结论 :盲针法能够有效用于针灸临床疗效的研究 ,针灸与现代康复理论相结合能有效改善急性期中风患者功能康复的疗效 ,SPECT -rCBF脑显像检查表明其作用机制可能系促进脑功能激活后的重组。

盲针法电针治疗中风的前瞻性临床对照研究

目的应用盲针技术研究电针对中风后偏瘫的疗效,并探讨其机制。方法为单盲法前瞻性随机对照临床研究,64例急性期中风患者随机分为治疗组和对照组,治疗组以常规电针治疗,对照组予以盲针通电治疗。在治疗前、治疗第10d和第20d行NIHSS、Fugl-Mcyer和 Barthel指数评分。在治疗前和治疗第20d行SPECT-rCBF脑显像检查,记录各脑区脑血流灌注(rCBF)情况。结果经治疗后,运动功能及日常生活能力指数均有提高,差异显著(P<0.05),且治疗组的双侧额叶皮质运动区rCBF明显增加(P<0.05)。结论盲针法能够有效用于针刺的临床疗效研究,针刺与现代神经康复理论相结合,能有效改善急性期中风患者的功能康复,其可能机制系促进脑功能激活后的重组。

老年人的脑可塑性:来自认知训练的证据

老年人大脑结构和功能衰退是其认知功能下降的重要原因。然而,老年人的大脑仍然保持了一定的可塑性。随着神经影像技术的发展,大量研究发现认知训练能够对老年人的大脑结构和功能产生积极影响:(1)在脑结构方面,表现为大脑皮层灰质体积增加、白质神经纤维连接增强;(2)在进行认知任务时,表现为脑功能网络发生重组;(3)在静息态脑功能方面,表现为脑自发活动功能性重组以及功能连接增强。未来的认知训练研究需要考察老年人大脑可塑性存在个体差异的多种影响因素,并通过纵向追踪研究来探讨大脑可塑性的保持性和迁移效应。

基于BDNF/TrkB通路探讨电针对脑缺血再灌注损伤大鼠学习记忆功能及突触可塑性的影响

目的:观察电针“百会”“四神聪”对脑缺血再灌注损伤(CIRI)大鼠缺血侧海马脑源性神经营养因子(BDNF)/酪氨酸激酶受体B(TrkB)通路、突触素(SYN)表达及白细胞介素-1β(IL-1β)、白细胞介素-18(IL-18)含量的影响,探究电针改善CIRI后学习记忆功能的作用及机制。方法:将48只SPF级雄性SD大鼠随机分为假手术组、模型组、电针组和非穴组,每组12只。模型组、电针组和非穴组大鼠采用改良Zea Longa线栓法制备CIRI模型。电针组予电针“四神聪”“百会”,疏密波,频率2 Hz/10 Hz,电流强度1 mA;非穴组电针双侧肋下非经非穴点,电针参数同电针组。两组干预均每次30 min,每天1次,持续7 d。干预期间,于每日固定时间测量大鼠体质量;于干预第1、3、7天观察各组大鼠神经功能缺损情况。干预前后采用小动物磁共振成像技术测量大鼠脑梗死体积。干预后,采用Morris水迷宫评价大鼠学习记忆功能;HE染色观察大鼠海马形态;免疫组化法检测大鼠缺血侧海马SYN阳性表达;Western blot法检测大鼠缺血侧海马BDNF、TrkB、SYN蛋白表达;ELISA法检测大鼠缺血侧海马IL-1β、IL-18含量。结果:干预第2~7天,与假手术组比较,模型组大鼠体质量下降(P<0.01);与模型组和非穴组比较,电针组大鼠体质量增加(P<0.01)。干预第1天,与假手术组比较,模型组、电针组和非穴组大鼠神经功能评分升高(P<0.01);干预第3、7天,模型组大鼠神经功能评分高于假手术组(P<0.01);干预第7天,电针组大鼠神经功能评分低于模型组与非穴组(P<0.05)。与假手术组比较,模型组大鼠逃避潜伏期延长(P<0.05),穿越平台次数减少(P<0.01);与模型组和非穴组比较,电针组大鼠逃避潜伏期缩短(P<0.05),穿越平台次数增加(P<0.01)。干预前,模型组、电针组和非穴组大鼠左侧脑室出现明显高信号梗死灶;干预后与模型组和非穴组比较,电针组大鼠脑梗死体积占比下降(P<0.01)。模型组与非穴组大鼠神经元细胞排列疏散且紊乱、胞质深染且胞核固缩;电针组大鼠神经元细胞数目、排列情况趋于假手术组,胞质深染及胞核固缩现象较模型组减轻。与假手术组比较,模型组大鼠缺血侧海马SYN阳性表达及BDNF、TrkB、SYN蛋白表达减少(P<0.01,P<0.05),IL-1β、IL-18含量升高(P<0.01);与模型组和非穴组比较,电针组大鼠缺血侧海马SYN阳性表达及BDNF、TrkB、SYN蛋白表达增加(P<0.01,P<0.05),IL-1β、IL-18含量下降(P<0.01)。结论:电针“百会”“四神聪”可能通过激活BDNF/TrkB信号通路转导,减轻神经炎性反应,促进突触可塑性恢复来改善CIRI大鼠学习记忆功能。

成年大鼠全臂丛根性撕脱伤后初级体感皮层可塑性变化的脑电生理研究

目的探讨成年大鼠一侧全臂丛根性撕脱伤后双侧初级体感皮层可塑性变化的规律。方法将30只SD雄性大鼠分为6组,分为正常对照组和全臂丛根性撕脱伤术后1d、7d、1个月、3个月、1年共5个时间组,每组5只。采用体感皮层诱发电位(somatosensory evoked potential,SEP)记录法,定量评价一侧全臂丛根性撕脱伤后双侧初级体感皮层(Sml)可塑性变化的时程。结果术后不同时间段电刺激患爪正中神经支配区,在双侧Sml均未诱发出SEP。电刺激健侧前爪正中神经支配区,在健爪同侧Sml未记录到SEP,只在其对侧Sml记录到SEP；但不同时间段的SEP位点数目均明显多于正常对照组。结论成年大鼠的初级体感皮层仍具有可塑性,一侧全臂丛根性撕脱伤后诱发了双侧Sml动态的功能重组。两大脑半球相对应的同位区域之间存在着维持半球间平衡和协调的特殊机制。健侧前爪体感代表区的扩大可提高健爪的感觉辨别能力,以部分代偿患肢感觉功能的丧失。

声带切除术患者声音嘶哑相关语音加工fMRI随访研究

目的采用朗读任务功能磁共振成像(fMRI)随访喉癌患者激光声带切除术前、术后嗓音嘶哑期、嗓音重建后期患者语言功能脑区激活,研究声音嘶哑、嗓音重建对语言功能脑区的影响。方法 16例早期喉癌患者进行术前、术后1周、术后2～3个月3次检查。刺激任务采用事件相关设计,视觉呈现,受试者朗读汉语名词任务。使用AFNI软件提取各个功能脑区的激活体素。对不同脑区术前、术后第一次、术第二次激活体素进行方差分析,有差异者进行两两比较。结果嗓音明显嘶哑期,患者左侧额下回激活体素多于术前及嗓音重建后期(F值分别为7.916、7.270,P值均<0.01)。嗓音重建后期激活体素多于术前、术后嗓音嘶哑期的脑区为左、右侧中央前回(F值分别为11.665、10.214、7.665、6.482,P值均<0.01)、额中回(F值分别为10.337、10.563、6.458、6.303,P值均<0.01)及辅助运动区(F值分别为14.343、14.095、7.945、7.947,P值均<0.01)。结论激光切除术后患者的声音嘶哑、嗓音调整、重建过程伴随着语言功能网络重塑性改变,左侧额下回前部、双侧额中回、双侧中央前回、双侧辅助运动区在音韵处理过程中功能不同。

脊髓损伤后脑结构与功能可塑性变化功能性磁共振成像研究进展

脊髓损伤(SCI)能引起大脑结构和功能可塑性变化,将影响到SCI后的预后评估和疗效评价。功能性磁共振成像(如fMRI,DTI)是评估SCI后脑结构和功能连接可塑性变化的无创性技术,本文旨在综述SCI后脑结构与功能可塑性变化功能性磁共振成像的研究进展。