Behavioral Effect of Short- and Long-Term Exercise on Motor Functional Recovery after Intracerebral Hemorrhage in Rats

Background

In this study, we investigated the effects of short- and long-term exercise on motor functional recovery following intracerebral hemorrhage (ICH) in rats.

The Effect of Cerebellar Transplantation and Enforced Physical Activity on Motor Skills and Spatial Learning in Adult Lurcher Mutant Mice

Lurcher mutant mice represent a model of olivocerebellar degeneration. They are used to investigate cerebellar functions, consequences of cerebellar degeneration and methods of therapy influencing them. The aim of the work was to assess the effect of foetal cerebellar graft transplantation, repeated enforced physical activity and the combination of both these types of treatment on motor skills, spontaneous motor activity and spatial learning ability in adult B6CBA Lurcher mice. Foetal cerebellar grafts were applied into the cerebellum of Lurchers in the form of solid tissue pieces. Enforced motor activity was realised through rotarod training. Motor functions were examined using bar, ladder and rotarod tests. Spatial learning was tested in the Morris water maze. Spontaneous motor activity in the open field was observed. The presence of the graft was examined histologically. Enforced physical activity led to moderate improvement of some motor skills and to a significant amelioration of spatial learning ability in Lurchers. The transplantation of cerebellar tissue did not influence motor functions significantly but led to an improvement of spatial learning ability. Mutual advancement of the effects of both types of treatment was not observed. Spontaneous motor activity was influenced neither by physical activity nor by the transplantation. Physical activity did not influence the graft survival and development. Because nerve sprouting and cell migration from the graft to the host cerebellum was poor, the functional effects of the graft should be explained with regard to its trophic influence rather than with any involvement of the grafted cells into neural circuitries.     

Visuomotor Gain Distortion Alters Online Motor Performance and Enhances Primary Motor Cortex Excitability in Patients With Stroke

Objectives: Determine if ipsilesional primary motor cortex (M1) in stroke patients processes online visuomotor discordance in gain between finger movement and observed feedback in virtual reality (VR). Materials and Methods: Chronic stroke patients flexed (N= 7) or extended (N= 1) their finger with real‐time feedback of a virtual hand presented in VR. Virtual finger excursion was scaled by applying a low‐gain (G_0.25), high‐gain (G_1.75), or veridical (G_1.00) scaling factor to real‐time data streaming from a sensor glove. Effects of visuomotor discordance were assessed through analysis of movement kinematics (joint excursion, movement smoothness, and angular velocity) and amplitude of motor evoked potentials (MEPs) elicited with transcranial magnetic stimulation applied to ipsilesional M1. Data were analyzed with a repeated‐measures analysis of variance (significance set at 0.05). Results: G_0.25 discordance (relative to veridical) leads to significantly larger joint excursion, online visuomotor correction evidenced by decreased trajectory smoothness, and significantly facilitated agonist MEPs. This effect could not be explained by potential differences in motor drive (background electromyographic) or by possible differences related to joint angle or angular velocity, as these variables remained invariant across conditions at the time of MEP assessment. M1 was not significantly facilitated in the G_1.75 condition. MEPs recorded in an adjacent muscle that was not involved in the task were unaffected by visual feedback in either discordance condition. These data suggest that the neuromodulatory effects of visuomotor discordance on M1 were relatively selective. Conclusions: Visuomotor discordance may be used to alter movement performance and augment M1 excitability in patients following stroke. Our data illustrate that visual feedback may be a robust way to selectively modulate M1 activity. These data may have important clinical implications for the development of future VR training protocols.     

NMDA受体和GABA受体拮抗剂对小鼠脑内多巴胺的影响

目的 观察兴奋性氨基酸受体拮抗剂和GABA受体拮抗剂对帕金森病（PD）模型动物全脑多巴胺（DA）含量的影响，为PD发病机制研究提供理论依据。方法 采用MPTP腹腔注射建立C57 BL小鼠PD模型，同时分别腹腔注射兴奋性氨基酸NMDA受体拮抗剂ketamine和GABA受体拮抗剂bicucullin．采用荧光分光光度计法测定各组小鼠全脑DA的含量。结果 ketamine＋MPTP组、bicucullin＋MPTP组与MPTP组及NS组比较，DA含量差异有统计学意义。结论 NMDA受体拮抗剂可抑制由MPTP引起的DA神经递质减少，GABA受体拮抗剂可增强MPTP引起的DA神经递质减少。     

Effects of Physical Exercise Interventions on Stereotyped Motor Behaviours in Children with ASD: A Meta-Analysis

Journal of Autism and Developmental Disorders - Studies have reported that physical exercise reduces maladaptive stereotyped motor behaviours (SMB) in children with ASD, but these intervention...     

The Value of Exercise Rehabilitation Program Accompanied by Experiential Music for Recovery of Cognitive and Motor Skills in Stroke Patients

Background

The aim of this study was to systematically assess the effects of exercise rehabilitation program accompanied by experiential music for clinical recovery.

运动再学习对缺血性卒中患者运动功能及其认知电位P300的影响

目的 研究运动再学习训练对缺血性卒中患者运动功能及其认知电位P300的影响。 方法 52名缺血性卒中患者运动再学习前后,对Berg平衡积分、Sheikh躯干控制积分、简式Fugl-Meyer运动功能评分及步行能力等指标进行评价,观察在运动功能改善的同时认知电位P300是否有改善。共治疗12周。 结果 运动再学习后缺血性卒中患者运动功能和认知功能显著改善,Berg平衡积分、Sheikh躯干平衡积分、简式Fugl-Meyer运动功能评分及步行能力等各指标治疗前后比较差异有统计学意义（P<0.01）,同时认知电位P300潜伏期比训练前明显缩短（P<0.01）,波幅较治疗前显著增高（P<0.01）。 结论 运动疗法在改善缺血性卒中者运动功能的同时对认知功能的有积极的恢复作用。     

急性Dieldrin中毒对C57BL小鼠纹状体多巴胺含量的影响

目的：探讨急性Ｄｉｅｌｄｒｉｎ（氧桥氯甲桥奈）中毒对Ｃ５７ＢＬ 小鼠纹状体多巴胺及其代谢产物含量的影响。方法：给３组小鼠分别喂食 Ｄｉｅｌｄｒｉｎ ５０ ｍｇ·ｋｇ－１体重、Ｄｉｅｌｄｒｉｎ ４０ ｍｇ·ｋｇ－１体重和等量的生理盐水,３ ｈ后处死小鼠,取纹状体匀浆用高效液相色谱－电化学检测法测定纹状体中多巴胺（ＤＡ）、５－羟色胺（５－ＨＴ）、高香草酸（ＨＶＡ）、５－羟基吲哚乙酸（５－ＨＩＡＡ）和去甲肾上腺素（ＮＡ）的含量。结果：喂食 Ｄｉｅｌｄｒｉｎ ５０ ｍｇ·ｋｇ－１体重能降低小鼠纹状体中 ＮＡ、ＤＡ及 ＨＶＡ的含量．结论：大剂量的Ｄｉｅｌｄｒｉｎ可影响小鼠纹状体中 ＤＡ的代谢．可能是致帕金森病的环境因素之一。     

The Effect of Minocycline on Motor Neuron Recovery and Neuropathic Pain in a Rat Model of Spinal Cord Injury

Objective

Minocycline, a second-generation tetracycline-class antibiotic, has been well established to exert a neuroprotective effect in animal models and neurodegenerative disease through the inhibition of microglia. Here, we investigated the effects of minocycline on motor recovery and neuropathic pain in a rat model of spinal cord injury.

Methods

To simulate spinal cord injury, the rats'' spinal cords were hemisected at the 10th thoracic level (T10). Minocycline was injected intraperitoneally, and was administered 30 minutes prior surgery and every second postoperative day until sacrifice 28 days after surgery. Motor recovery was assessed via the Basso-Beattie-Bresnahan test. Mechanical hyperalgesia was measured throughout the 28-day post-operative course via the von Frey test. Microglial and astrocyte activation was assessed by immunohistochemical staining for ionized calcium binding adaptor molecule 1 (Iba1) and glial fibrillary acidic protein (GFAP) at two sites: at the level of hemisection and at the 5th lumbar level (L5).

Results

In rats, spinal cord hemisection reduced locomotor function and induced a mechanical hyperalgesia of the ipsilateral hind limb. The expression of Iba1 and GFAP was also increased in the dorsal and ventral horns of the spinal cord at the site of hemisection and at the L5 level. Intraperitoneal injection of minocycline facilitated overall motor recovery and attenuated mechanical hyperalgesia. The expression of Iba1 and GFAP in the spinal cord was also reduced in rats treated with minocycline.

Conclusion

By inhibiting microglia and astrocyte activation, minocycline may facilitate motor recovery and attenuate mechanical hyperalgesia in individuals with spinal cord injuries.     

Influence of Physical Exercise on Traumatic Brain Injury Deficits: Scaffolding Effect

Traumatic brain injury (TBI) may be due to a bump, blow, or jolt to the head or a penetrating head injury that disrupts normal brain function; it presents an ever-growing, serious public health problem that causes a considerable number of fatalities and cases of permanent disability annually. Physical exercise restores the healthy homeostatic regulation of stress, affect and the regulation of hypothalamic-pituitary-adrenal axis. Physical activity attenuates or reverses the performance deficits observed in neurocognitive tasks. It induces anti-apoptotic effects and buttresses blood-brain barrier intactness. Exercise offers a unique non-pharmacologic, non-invasive intervention that incorporates different regimes, whether dynamic or static, endurance, or resistance. Exercise intervention protects against vascular risk factors that include hypertension, diabetes, cellular inflammation, and aortic rigidity. It induces direct changes in cerebrovasculature that produce beneficial changes in cerebral blood flow, angiogenesis and vascular disease improvement. The improvements induced by physical exercise regimes in brain plasticity and neurocognitive performance are evident both in healthy individuals and in those afflicted by TBI. The overlap and inter-relations between TBI effects on brain and cognition as related to physical exercise and cognition may provide lasting therapeutic benefits for recovery from TBI. It seems likely that some modification of the notion of scaffolding would postulate that physical exercise reinforces the adaptive processes of the brain that has undergone TBI thereby facilitating the development of existing networks, albeit possibly less efficient, that compensate for those lost through damage.     

Intranasal and Subcutaneous Administration of Dopamine D3 Receptor Agonists Functionally Restores Nigrostriatal Dopamine in MPTP-Treated Mice

Parkinson’s disease (PD) is a neurodegenerative disease with a hallmark motor defect caused by the death of dopaminergic neurons in the substantia nigra. Intranasal drug administration may be useful for Parkinson’s treatment because this route avoids first-pass metabolism and increases bioavailability in the brain. In this study, we investigated the neuroprotection/neurorestoration effect of dopamine D3 receptor (D3R) agonists administered via both intranasal and subcutaneous routes in the MPTP (1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine)-induced PD mouse model. Furthermore, we employed D3R knock-out mice to validate the dependence on D3R signaling. We found that in wild-type mice, but not D3 receptor knockout mice, both intranasal and subcutaneous administration of D3R agonists rescue dopamine (DA) depletion in the striatum as well as DA neuronal death in the substantia nigra after MPTP treatment. Moreover, subcutaneous 7-OH-DPAT administration significantly improved gait performance (stride length and overall running speed) of MPTP-lesioned mice after 7 and 14 days of recovery. In addition, the distribution of D3 agonist 7-OH-DPAT was measured in designated brain areas by mass spectrometry analysis after subcutaneous and intranasal administration. Our data suggest that intranasal administration of D3R agonist would be a practical approach to treat PD.     

Early Effects of FGF-2 on Glial Cells in the MPTP-Lesioned Striatum

Fibroblast growth factor-2 (FGF-2), locally administered in gelfoam to the striatum of mice treated with the neurotoxic drug 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine (MPTP), has restorative and neuroprotective effects on dopaminergic neurons and associated striatal transmitter systems. Most of the beneficial alterations are apparently indirect. FGF-2 must therefore act through a series of cellular and molecular intermediate steps, which have not been explored. We have previously shown that FGF-2 does not significantly affect the astroglial reaction at the time, when the neuroprotective effect of FGF-2 reaches a peak (Day 11). In this study we have investigated the effect of FGF-2 at earlier time points after MPTP treatment. We report now that as early as 6 h after administration of the gelfoam containing either FGF-2 or control protein, FGF-2 immunoreactivity disappears from astroglial nuclei, while appearing in small ramified GFAP- and S-100-negative cells, most likely microglia. At 18 h, numbers and staining intensities of GFAP-ir astroglial cells are greater in FGF-2- than in cytochrome C-treated animals. At this time FGF-2-ir reappears in astroglia nuclei of cytochrome C-treated animals, but remains undetectable in the striatum carrying the FGF-2-containing gelfoam. Ramified GFAP/S-100-negative presumed microglial cells are now intensely ir for FGF-2. Signs of an FGF-2-mediated astrogliotic reaction are very pronounced at 18 h and 2 days, but no longer at 11 days, when the astrogliosis reaction has become equally strong in FGF-2- and cytochrome C-treated striata. Our results suggest that administration of FGF-2 to the MPTP-lesioned striatum has early effects on astro- and presumed microglia cells, notably on the nuclear FGF-2-ir of astrocytes. These changes may be involved in mediating the neuro-protective effects of FGF-2 in the MPTP-model of Parkinsonism.     

The Structural and Functional Characteristics of the Motor End Plates of Dysferlin-Deficient Mice

The molecular mechanisms that underlie neuromuscular junction plasticity are complex and remain to be fully elucidated. Experimental models of various forms of impaired motor activity may be promising for their study. The dysferlin protein plays a key role in the multimolecular complex, which maintains sarcolemma integrity and the functioning of skeletal muscle cells. We studied the structural and functional characteristics of the diaphragm muscle motor end plates of dysferlin-deficient Bla/J mice (a model of dysferlinopathy), dystrophin-deficient mdx mice (a model of Duchenne muscular dystrophy), and control C57Bl/6 mice. Increased end plate fragmentation and a decrease in the area of individual fragments were observed in mdx mice and absent in Bla/J mice, which indicates a difference in these models of myodystrophy from these characteristics. However, end plates of both mice lines were characterized by a decrease in the density of distribution of nicotinic acetylcholine receptors, as well as by membrane depolarization, presumably, due to altered functional interaction between the α2 isoform of Na,K-ATPase and the nicotinic acetylcholine receptors.     

Effect of Task-Based Mirror Therapy on Motor Recovery of the Upper Extremity in Chronic Stroke Patients: A Pilot Study

Abstract

Background and Aims: Mirror therapy (MT) is an alternative therapeutic intervention that uses the interaction of visuomotor-proprioception inputs to enhance movement performance of the impaired limb. Despite strong evidence for task-specific training in stroke, MT has been investigated using nontask movements. The aim of this pilot study was to assess the effectiveness of task-based MT on motor recovery of the upper extremity in chronic stroke patients. Method: In a pretest-posttest single-group design, a convenience sample of 13 chronic stroke patients at an occupational therapy department of a rehabilitation institute was assessed on a task-based MT intervention. Participants received a task-based MT program, performing various tasks by the less affected upper extremity and observing in the mirror box along with conventional management, 4 days per week for 4 weeks. Fugl-Meyer Assessment (FMA), which includes subsection upper extremity (FMA-UE) and subpart upper arm (FMA-UA) and hand (FMA-WH), was used as an outcome measure. Results: Participants showed no significant improvement for FMA-UE and FMA-UA at postassessment. FMA-UE changed from 43% to 51%. Post FMA-UA score showed only 2% improvement. However, there was statistically significant improvement on mean scores of FMA-WH at postassessment (16.21 ± 3.06) as compared with the prescores (12.29 ± 3.1; P < .05). FMA-WH improved from 41% to 54%. Conclusions: The preliminary findings suggest that task-based MT is effective in improving wrist and hand motor recovery in chronic stroke patients. Further studies in the form of randomized trials are needed to validate its effectiveness.     

Coordinated Postnatal Maturation of Striatal Cholinergic Interneurons and Dopamine Release Dynamics in Mice

Dynamic changes in motor abilities and motivated behaviors occur during the juvenile and adolescent periods. The striatum is a subcortical nucleus critical to action selection, motor learning, and reward processing. Its tonically active cholinergic interneuron (ChI) is an integral regulator of the synaptic activity of other striatal neurons, as well as afferent axonal projections of midbrain dopamine (DA) neurons; however, little is known about its development. Here, we report that ChI spontaneous activity increases during postnatal development of male and female mice, concomitant with a decreased afterhyperpolarization (AHP). We characterized the postnatal development of four currents that contribute to the spontaneous firing rate of ChIs, including I_SK, I_A, I_h, and I_NaP. We demonstrated that the developmental increase in I_NaP drives increased ChI firing rates during the postnatal period and can be reversed by the I_NaP inhibitor, ranolazine. We next addressed whether immature cholinergic signaling may lead to functional differences in DA release during the juvenile period. In the adult striatum, nicotinic acetylcholine receptors (nAChRs) prevent linear summation of DA release in response to trains of high-frequency stimuli. We show that, in contrast, during the second postnatal week, DA release linearly sums with trains of high-frequency stimuli. Consistently, nAChR antagonists exert little effect on dopamine release at postnatal day (P)10, but enhance the summation of evoked DA release in mice older than postnatal day P28. Together, these results reveal that postnatal maturation of ChI activity is due primarily to enhanced I_NaP and identify an interaction between developing cholinergic signaling and DA neurotransmission in the juvenile striatum.SIGNIFICANCE STATEMENT Motor skills and motivated behavior develop rapidly in juvenile rodents. Recent work has highlighted processes that contribute to the postnatal maturation of striatal principal neurons during development. The functional development of the striatal cholinergic interneuron (ChI), however, has been unexplored. In this study, we tracked the ontogeny of ChI activity and cellular morphology, as well as the developmental trajectory of specific conductances that contribute to the activity of these cells. We further report a link between cholinergic signaling and dopamine (DA) release, revealing a change in the frequency-dependence of DA release during the early postnatal period that is mediated by cholinergic signaling. This study provides evidence that striatal microcircuits are dynamic during the postnatal period and that they undergo coordinated maturation.     

百草枯对小鼠纹状体区多巴胺D1受体信号转导的影响

目的观察百草枯对小鼠纹状体区多巴胺D1受体信号转导的影响.方法用口服百草枯的途径,建立小鼠帕金森病模型;应用液闪测定技术测定百草枯对小鼠纹状体区DARPP-32(Mr=32 000)磷酸化程度的影响.结果给予小鼠口服百草枯10 mg*kg-1*d-1连续4个月后,纹状体区DARPP-32的32P结合位点增加77.4%(P＜0.01).结论百草枯可能通过cAMP/PKA系统减弱体内DARPP-32的磷酸化程度,调节其对多巴胺D1受体信号转导途径的作用.