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Lentivector-mediated delivery of GDNF protects complex motor functions relevant to human Parkinsonism in a rat lesion model.

Although viral vector-mediated delivery of glial cell-line derived neurotrophic factor (GDNF) to the brain has considerable potential as a neuroprotective strategy in Parkinson's disease (PD), its ability to protect complex motor functions relevant to the human condition has yet to be established. In this study, we used an operant task that assesses the selection, initiation and execution of lateralized nose-pokes in Lister Hooded rats to assess the efficacy with which complex behaviours are protected against neurotoxic lesions by prior injection of a lentiviral vector expressing GDNF. Unilateral injection of 6-hydroxydopamine (6-OHDA) into the medial forebrain bundle (MFB) caused rats to attempt fewer trials and to make more procedural errors. Lesioned rats also developed a pronounced ipsilateral bias, with a corresponding drop in contralateral accuracy. They were also slower to react to contralateral stimuli and to execute movements bilaterally. Rats that were pre-treated 4 weeks prior to lesion surgery with an equine infectious anaemia virus (EIAV) vector carrying GDNF [EIAV-GDNF, injected into the striatum and above the substantia nigra (SN)] performed significantly better on all of these parameters than control rats. In addition to the operant task, EIAV-GDNF successfully rescued contralateral impairments in the corridor, staircase, stepping and cylinder tasks, and prevented drug-induced rotational asymmetry. This study confirms that GDNF can protect against 6-OHDA-induced impairments in complex as well as simple behaviours, and reinforces the use of EIAV-based vectors for the treatment of PD.

Amphetamine↗

[Motor function evaluation in merosin-deficient congenital muscular dystrophy children].

Congenital muscular dystrophy (CMD) is a heterogeneous group of disorders characterized by early onset of hypotonia and weakness. Almost 50% of the cases are caused by primary deficiency of a protein named merosin (MD), and present a homogenous phenotype with a severe motor and respiratory involvement. Eleven children with clinical and histological diagnosis of CMD-MD, aged of 3 to 15 years, were studied using the manual muscle testing (Medical Research Council), goniometric analysis, motor ability and day life activities (Barthel index) scales, with the objective to characterize the main motor function limitations. The muscular groups most affected were cervical flexors, paravertebral and proximal portions of limbs. The muscular groups of upper limbs were as affected as the lower limbs, and the extensors were more affected than the flexors groups. All children had severe muscular retractions on the hip, knee and elbow. Other frequent deformities were scoliosis and equinus-varum feet. No children presented the motor ability to walk, stand up and crawl; and all of them were classified as dependents or semi-dependents in the day life activities scale. Our findings confirm the severe and diffuse involvement of skeletal muscle in CMD-MD patients, producing serious motor limitations and deformities.

Activities of Daily Living↗

Corticotropin-releasing factor receptors and stress-related alterations of gut motor function.

Over the past few decades, corticotropin-releasing factor (CRF) signaling pathways have been shown to be the main coordinators of the endocrine, behavioral, and immune responses to stress. Emerging evidence also links the activation of CRF receptors type 1 and type 2 with stress-related alterations of gut motor function. Here, we review the role of CRF receptors in both the brain and the gut as part of key mechanisms through which various stressors impact propulsive activity of the gastrointestinal system. We also examine how these mechanisms translate into the development of new approaches for irritable bowel syndrome, a multifactorial disorder for which stress has been implicated in the pathophysiology.

Anxiety↗

Motor functional and morphological findings following end-to-side neurorrhaphy in the rat model.

Nerve repair cannot always be achieved by the conventional end-to-end technique. This study evaluated the functional recovery of nerves repaired with end-to-side neurorrhaphy in a rat model. The right peroneal nerves of 80 female rats were transected and divided into four groups. In group A, the nerve ends were separated and remained unrepaired; in group B, the distal peroneal ends were directly sutured to the epineurium of the tibial nerves in end-to-side fashion; in group C, the distal ends were sutured through an epineurial window at the repair site in end-to-side fashion; and in group D, the nerve ends were reconnected by the traditional end-to-end technique. Evaluation included gait analysis by calculation of a peroneal functional index, measurement of contractile function of the extensor digitorum longus muscle, wet weight of the extensor digitorum longus, and histological examination. The findings of this study suggested the following: (a) end-to-side neurorrhaphy allows effective motor functional recovery, demonstrated by earlier improvement of the peroneal functional index, stronger muscle contractile function, greater muscle weight, and higher density of regenerated axons compared with unrepaired nerves; (b) removal of the epineurium of the donor nerve at the nerve coaptation site increases the effectiveness of end-to-side neurorrhaphy, but the epineurium appears to be a partial barrier to axonal regeneration; (c) removal of the epineurium does not affect the structure and function of the donor nerve; and (d) end-to-end repair achieved the best functional recovery among the four groups; therefore, end-to-side repair should be considered as a potential alternative only when no proximal nerve is available.

Animals↗

Disturbance of motoric function as behavioral measure of impaired cerebral circulation in mice.

Aim of the present experiments was to elaborate an experimental model exhibiting the functional consequences of a moderate impairment of cerebral circulation sensitive enough for testing the long-term cerebroprotective effect of different drugs. In preliminary experiments mice survived unilateral occlusion of the carotid artery. This intervention, however, severely impaired the motor skill of the animals as measured by their activity on the rotating treadmill. Motimeter activity was also diminished following unilateral carotid occlusion. Somewhat unexpectedly, a more complex pattern of learned behavior in a one-trial learning passive avoidance paradigm was only modestly affected by unilateral carotid occlusion. Papaverine (2.0 mg/kg) normalized the motor incoordination measured on the rotating treadmill. The data suggest that impaired motoric function, as a result of unilateral carotid occlusion, might be a useful experimental tool to analyse functional consequences of impaired cerebral circulation and a sensitive test for screening of drugs with presumed cerebroprotective action.

Animals↗

Language and motor functions activate calcified hemisphere in patients with Sturge-Weber syndrome: a positron emission tomography study.

This study examines whether or not in Sturge-Weber syndrome hypoperfused brain areas that are affected by calcification continue to retain some function and participate in language and motor activations. [15O]-Water positron emission tomography (PET) was used for brain mapping of these functions in two patients with extensive unilateral calcification and hypoperfusion and in one patient with calcification and hypoperfusion restricted to the left posterior region. Task-related regional cerebral blood flow changes suggest that (1) hypoperfused areas may become activated during language and motor performance, and (2) progressive calcification in Sturge-Weber syndrome is associated with functional reorganization in the language and motor domains. Interhemispheric reorganization appears to be more pronounced for language than for motor functions.

Adolescent↗

Instrumentally detected changes in motor functioning in patients with low levels of antipsychotic dopamine D2 blockade.

Extrapyramidal side-effects (EPSE) of antipsychotic medication are related to the occupancy of dopamine D2 receptors and there appears to be a threshold of D2 occupancy below which clinically EPSE are unlikely to occur. It is unclear whether there are motor changes produced by 'subthreshold' levels of D2 occupancy that are not detectable by clinical examination. This study was designed to investigate whether a number of electromechanical instrumental techniques could detect 'subthreshold' motor changes and whether these changes correlate with dopamine D2 occupancy as measured by [11C]-raclopride PET scan. Twenty medication naïve patients were studied before and during treatment with low dose haloperidol. Instrumental techniques detected an asymmetrical worsening in motor function with drug treatment despite the failure of the group to experience significant EPSE. These changes did not correlate with D2 occupancy and measurements of rigidity, tremor, and bradykinesia did not closely inter-correlate.

Adult↗

Lateralization of sensory and motor functions in human neonates.

Lateral differences in some motor and sensory functions were examined in 89 full-term normal newborns, 2 to 4 days old. They were divided in two groups, according to the cerebral dominance in the family: Group A (70 subjects), offspring of right-handed parents and siblings, and Group B (19 subjects), with at least one parent or sibling left-handed or ambidextrous. Only subjects of Group A showed a marked tendency to spend more time with the head to right as opposed to the left, to turn right after release from the midline position, to have their heads right 5 min. later, to lead with the right leg on the placing response. The two groups were significantly different from each other on these tests. Differences were not observed for stepping, tactile responses, asymmetrical tonic neck reactions in either of the two groups. The results confirm the existence of lateral differentiations of neurological functions in the newborn and stress the presence of genetic factors in these phenomena.

Dominance, Cerebral↗

Nitric oxide and gall-bladder motor function.

BACKGROUND: The L-arginine: nitric oxide (NO) pathway has been shown to be important in the regulation of intestinal motility and NO may be the mediator for nonadrenergic noncholinergic (NANC) neurotransmission. AIM: To determine the role of the L-arginine: NO pathway in gall-bladder motor function. METHODS: Strips of fresh bovine and human gall-bladders were stimulated with cholecystokinin (CCK). The effects of glyceryl trinitrate (GTN), sodium nitroprusside and Kreb's solution upon CCK-stimulated muscle contraction were examined. The effect of the NO synthase inhibitor, L-NG-monomethyl-arginine (L-NMMA) upon basal muscle tone was also examined. Ten human gall-bladders were immunohistochemically stained for nitric oxide synthase (NOS) and product 9.5 to identify neurones. Postprandial gall-bladder emptying was measured on separate occasions in six healthy volunteers during systemic intravenous infusion of normal saline; glyceryl trinitrate; sodium nitroprusside (SNP), hydralazine and L-NMMA. RESULTS: In the in vitro study, GTN and SNP significantly reduced the tension of CCK-stimulated muscle contraction whilst Kreb's solution had no effect. L-NMMA increased tonic and phasic muscle contractions. Immunohistochemical staining for NOS was consistently absent in human gall-bladders. In the in vivo study, both GTN and SNP caused significant impairment of gall-bladder emptying; the ejection fraction was only 50% at the end of the study period involving these infusates, this contrasted with ejection fractions in excess of 80% during infusions with hydralazine, saline and L-NMMA. CONCLUSION: Pharmacological doses of NO donors impair postprandial gall-bladder emptying in vivo and relax gall-bladder smooth muscle in vitro. However, negative immunohistochemical staining suggest NOS is unlikely to be the neurotransmitter for NANC innervation regulating gall-bladder motility.

Adult↗

The effect of sildenafil on oesophageal motor function in healthy subjects and patients with nutcracker oesophagus.

Type 5 phosphodiesterase terminates the action of nitric oxide (NO) induced 3',5'-cyclic monophosphate (cGMP). Sildenafil inhibits this phosphodiesterase, increases cellular cGMP concentrations and enhances NO-induced smooth muscle relaxation. We investigated the effect of sildenafil on the oesophageal motor function of healthy subjects and patients with nutcracker oesophagus. Eight healthy volunteers and nine patients with nutcracker oesophagus participated in this study. The participants underwent oesophageal manometries on two separate days after either 20 mL of distilled water or 0.8 mg kg-1 sildenafil dissolved in 20 mL of water was infused into the stomach. Lower oesophageal sphincter (LOS) resting pressure, the duration of LOS relaxation and the amplitudes of oesophageal pressure waves were examined before, and 7.5, 15, 30 and 60 min after either placebo or sildenafil. In both healthy subjects and patients with nutcracker oesophagus, sildenafil decreased resting LOS pressure and the amplitude of peristaltic pressure waves at 3, 8 and 13 cm above LOS. Sildenafil also prolonged the duration of LOS relaxation. It had no effect on the velocity of peristalsis or the amplitude of peristaltic pressure waves 18 cm above LOS. Sildenafil may be considered as an alternative treatment in nutcracker oesophagus although there are several limitations to be overcome.

Adult↗

Cognitive and motor functioning in a patient with selective infarction of the left basal ganglia: evidence for decreased non-routine response selection and performance.

Focal damage to the basal ganglia is relatively rare, and little is known about the cognitive effects of damage to specific basal ganglia structures. A 28-year-old, highly educated male (patient RI) sustained a unilateral left ischemic infarction involving primarily the putamen and secondarily the head of the caudate and the anterior internal capsule. Two detailed neuropsychological assessments, at 3 and 16 months post-infarction, revealed that a majority of cognitive abilities were spared. RI's general intelligence, simple attention, concept formation, cognitive flexibility, and explicit memory were unaffected. Select cognitive abilities were affected, and these appeared to be related to direct involvement of the putamen and/or to indirect disruption of circuits between the basal ganglia and frontal lobes. Consistent with involvement of the left putamen, RI showed micrographia with his right hand. Interestingly, his micrographia was context-dependent, appearing only when verbal expression was involved (e.g., present when writing spontaneously, but not when copying sentences or when drawing). Evidence of disruption to frontal systems included variably decreased sustained attention, mildly decreased ability to generate words and to generate ideas, and significantly impaired abstraction ability in both verbal and visual modalities. Although there are several possible interpretations for these findings, this pattern of cognitive and motor functioning is consistent with neuroimaging research suggesting that the frontal/subcortical circuit between the putamen and frontal motor areas plays a role in non-routine response selection and performance.

Adult↗

[The effect of selective dorsal rhizotomy on motor function in patients with infantile cerebral palsy].

The authors analyze the outcomes of surgical treatment in 15 CP patients with lower paraparesis who had been treated with selective dorsal rhizotomy at the L2-S2 level. All the patients were examined by neurological study, EMG, EEG, visual evoked potential (VEP) recording and motor reaction time estimation. Based on the findings, it is suggested that SPR lumbosacral spinal level may affect cerebral function. Some motor functional changes are associated with this impact. Possible mechanisms of these changes are discussed.

Adolescent↗

Motor functions: associated primitive reflex profiles.

The results of reflex/motor activity interactions in 177 normal infants are evaluated. The asymmetrical tonic neck reflex, tonic labyrinthine reflex-supine, and Moro reflexes were assessed for each child at birth and at intervals up to 12 months. Ages of rolling prone to supine, rolling supine to prone, and sitting alone were elicited from parents. The effects of the primitive reflexes on early motor activity were assessed, and statistically significant correlations were demonstrated between decreased reflex activity and the emergence of motor milestones. The distinctive association of reflex activity with motor function suggests the interaction of several reflexes (a primitive reflex profile) rather than the influence of isolated reflex activity. Such patterns support the hypothesis that decreasing primitive reflex activity is associated with the onset of volitional motor activity in normal infants.

Developmental Disabilities↗

Enlargement of cervical spinal cord correlates with improvement of motor function in upper extremities after laminoplasty for cervical myelopathy.

OBJECTIVE: The correlation between postoperative spinal cord enlargement at the most compressive disc level and clinical outcome is controversial. The relationship between spinal cord enlargement at neurologically symptomatic disc level and clinical recovery has not been explored. The purpose of this study was to clarify the relationship between postoperative spinal cord enlargement at neurologically symptomatic disc level and neurologic outcome. METHODS: We studied 55 consecutive patients between 1995 and 2002. All patients underwent preoperative neurologic examination to determine the neurologically symptomatic disc level of the spinal cord and computed tomographic myelography twice before and 4 weeks after laminoplasty. The cross-sectional areas of both spinal cord and dural sac from C3/4 to C7/T1 disc levels were measured on computed tomographic myelography images. The Japanese Orthopedic Association scoring system was used for clinical evaluation before and 1 year after surgery. RESULTS: Total score improved significantly from 10.2+/-2.8 (SD) to 13.0+/-3.0 after operation. Motor and sensory function scores of upper and lower extremities also improved significantly. The enlargement of spinal cord area at the neurologically symptomatic disc level correlated significantly with improvement in motor function scores of upper extremities (rs=0.421 P=0.0052). However, there were no significant relationships between the enlargement of the spinal cord at the most compressive disc level or that at the dural sac and any categories of Japanese Orthopedic Association scoring system. CONCLUSION: Postsurgical enlargement of the cervical spinal cord at the neurologically symptomatic disc level at 4 weeks postoperatively correlated with recovery of motor function of the upper extremities at 1 year.

Cervical Vertebrae↗

Manometric study of the activity of alizapride on the motor function of the human sphincter of Oddi.

Alizapride is a potent antiemetic, acting as a dopamine receptor antagonist on the chemoreceptor trigger zone with few gastrokinetic properties. Little is known of its activity on the human sphincter of Oddi (SO). The aim of this study was to assess the effect of alizapride on SO motor function and to evaluate a possible use of alizapride in premedication for endoscopy of the upper digestive tract. We selected ten patients who underwent retrograde cholangiopancreaticography, but had no evidence of biliary or pancreatic disease. Endoscopic manometry was applied before and for 10 min after administration of alizapride 100 mg i.v. No significant modification of basal pressure or phasic activity was observed. Alizapride can be proposed as an antiemetic in patients with biliary disorders.

Adult↗

[The action of an impulse magnetic field on the motor function recovery of the peripheral nerve trunks].

The cut sciatic nerve trunk was sutured perineurally to study in chronic rabbit experiments of the neuromuscular functional recovery upon the exposure to impulse magnetic field with the intensity 1.2 T. Nonexposed animals served control. Myographic activity of reinnervated crural muscles in the irradiated animals recovered two times more rapidly compared to the controls, so did motor function of the limb operated on. It is inferred that impulse magnetic field produces therapeutic and preventive effect on neurodystrophy resultant from the nerve dissection.

Animals↗

Effect of peroxynitrite on motor function of the opossum esophagus.

Nitric oxide (NO*) is a mediator of esophageal motility. Esophageal dysmotility accompanies esophagitis. During inflammation, superoxide and NO* form peroxynitrite (ONOO-), a reactive molecule that alters cellular function. We tested the hypotheses that ONOO- affects esophageal motility and is produced in association with esophagitis. Transverse muscle strips from the opossum esophagus were stimulated by an electrical field, and nitrotyrosine immunoblots were performed. Peroxynitrite, its decomposed form, or NaNO2 relaxed the lower esophageal sphincter (LES) and attenuated the off response. These effects were inhibited by oxyhemoglobin (Hgb). An antagonist of guanylate cyclase, 1H[1,2,4]oxadiazole[4,3]quinoxalin-1-one (ODQ), inhibited the LES relaxation produced by ONOO-. Nitrotyrosine, a footprint for ONOO- production, was detected in inflamed esophagus. These studies support the hypotheses that ONOO alters esophageal motor function and is formed in association with esophagitis. It is possible that some of the esophageal motor dysfunction seen with esophagitis may be related to the formation of ONOO-.

Animals↗

Enriched environment improves motor function in intact and unilateral dopamine-depleted rats.

Previous studies have suggested that experience and environmental conditions can affect the progression and severity of symptoms in Parkinson's disease. Furthermore, earlier reports have indicated that enriched environment promotes the survival of dopaminergic grafts in a rat model of Parkinson's disease. Here we investigated whether environmental enrichment affects normal motor function and the severity of dopamine depletion in a rat model of Parkinson's disease. Adult female Long-Evans rats were pre-trained and tested daily in a skilled reaching task. One group of rats was placed in an enriched environment while one group was housed under standard conditions. During this time period, reaching success of animals exposed to the enriched environment improved as compared with animals living in standard housing. The animals remained in the two housing conditions for six weeks prior to receiving unilateral infusion of the neurotoxin 6-hydroxydopamine into the nigrostriatal bundle. The daily behavioral testing continued up to four weeks after lesion. The observations showed that rats housed in an enriched environment significantly improved in reaching success during the first three weeks after lesion as compared with rats housed in the standard condition. Qualitative movement analysis, drug-induced rotation and histological findings indicate that compensatory processes in particular might have accounted for the behavioral improvements. These data are discussed in relation to possible mechanisms of experience-dependent modulation of the pathology of Parkinson's disease.

Animals↗