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Ethanol and delta9-tetrahydrocannabinol interactive effects on human perceptual, cognitive and motor functions. II.

Fifteen paid student volunteers (10 male, five female) were used in a double-blind crossover experiment to further investigated the effects of delta9-tetrahydrocannabinol (THC), alone and in combination with ethanol, on perceptual, cognitive and motor functions. Both ethanol (0-54 g/kg) and THC (15 MG/70 KG) WERE GIVEN ORALLY. Ethanol was not very effective in in+uencing performance but this dose of THC produced marked decrements, predominantly in the latter part of the experiment. When they were given together, an early additive effect was apparent, but later, there was a suggestion of antagonism in that subjects who received the drug combination performed better than those who were given THC along. The interaction between THC and ethanol was considered to be complex.

Adolescent↗

GM1 ganglioside treatment protects against long-term neurotoxic effects of neonatal X-irradiation on cerebellar cortex cytoarchitecture and motor function.

Exposure of neonatal rats to a 5 Gy dose of X-irradiation induces permanent abnormalities in cerebellar cortex cytoarchitecture (disarrangement of Purkinje cells, reduction of thickness of granular cortex) and neurochemistry (late increase in noradrenaline levels), and motor function (ataxic gait). The neuroprotective effects of gangliosides have been demonstrated using a variety of CNS injuries, including mechanical, electrolytic, neurotoxic, ischemic, and surgical lesions. Here, we evaluated whether systemically administered GM1 ganglioside protects against the long-term CNS abnormalities induced by a single exposure to ionizing radiation in the early post-natal period. Thus, neonatal rats were exposed to 5 Gy X-irradiation, and subcutaneously injected with one dose (30 mg/kg weight) of GM1 on h after exposure followed by three daily doses. Both at post-natal days 30 and 90, gait and cerebellar cytoarchitecture in X-irradiated rats were significantly impaired when compared to age-matched controls. By contrast, both at post-natal days 30 and 90, gait in X-irradiated rats that were treated with GM1 was not significantly different from that in non-irradiated animals. Furthermore, at post-natal day 90, cerebellar cytoarchitecture was still well preserved in GM1-treated, X-irradiated animals. GM1 failed to modify the radiation-induced increase in cerebellar noradrenaline levels. Present data indicate that exogenous GM1, repeatedly administered after neonatal X-irradiation, produces a long-term radioprotection, demonstrated at both cytoarchitectural and motor levels.

Animals↗

A partial GDNF depletion leads to earlier age-related deterioration of motor function and tyrosine hydroxylase expression in the substantia nigra.

Glial cell line-derived neurotrophic factor (GDNF) is a trophic factor for peripheral organs, spinal cord, and midbrain dopamine (DA) neurons. Levels of GDNF deteriorate in the substantia nigra in Parkinson's disease (PD). A heterozygous mouse model was created to assess whether chronic reductions in this neurotrophic factor impact motor function and the nigrostriatal dopamine system during the aging process. Due to the important role GDNF plays in kidney development, kidney function and histology were assessed and were found to be normal in both wild-type (WT) and GDNF+/- mice up to 22 months of age. Further, the animals of both genotypes had similar weights throughout the experiment. Locomotor activity was assessed for male WT and GDNF+/- mice at 4-month intervals from 4 to 20 months of age. Both GDNF+/- and WT mice exhibited an age-related decline in horizontal activity, although this was found 4 months earlier in GDNF+/- mice, at 12 months of age. Comparison of young (8 month old) and aged (20 month old) GDNF+/- and WT mice on an accelerating rotarod apparatus established a deficiency for aged but not young GDNF+/- mice, while aged WT mice performed as well as young WT mice on this task. Finally, both WT and GDNF+/- mice exhibited an age-related decrease in substantia nigra TH immunostaining, which was accelerated in the GDNF+/- mice. These behavioral and histological alterations suggest that GDNF may be an important factor for maintenance of motor coordination and spontaneous activity as well as DA neuronal function during aging, and further suggest that GDNF+/- mice may serve as a model for neuroprotective or rescue studies.

Age Factors↗

Chylomicron components mediate intestinal lipid-induced inhibition of gastric motor function.

Lipid, particularly long-chain triglyceride, initiates feedback regulation of gastrointestinal function. To determine whether the site of action of lipid is pre- or postabsorptive, we investigated the ability of mesenteric lipid-fed lymph to inhibit gastric motor function. Lymph was collected from awake lymph-fistula rats during intestinal infusion with either a glucose-saline maintenance solution or lipid. Intra-arterial injection of lymph collected during intestinal lipid infusion significantly inhibited gastric motility in anesthetized recipient rats compared with injection of equivalent amounts of triglyceride or lymph collected during intestinal infusion of maintenance solution. Lymph collected from rats during lipid infusion with Pluronic L-81 [an inhibitor of chylomicron formation and apolipoprotein (apo) A-IV secretion] compared with lymph injection from donor animals treated with Pluronic L-63 (a noninhibitory control for Pluronic L-81) was significantly less potent. Injection of purified recombinant apo A-IV significantly inhibited gastric motility. Products of lipid digestion and absorption, other than fatty acids or triglyceride, released by the intestine during lipid digestion likely serve as signals to initiate intestinal feedback regulation of gastrointestinal function. Most likely, apo A-IV is one of the signals involved.

Animals↗

Delayed infusion of GDNF promotes recovery of motor function in the partial lesion model of Parkinson's disease.

Here we studied the effects of glial cell line-derived neurotrophic factor (GDNF) in a rat model that represents the symptomatic stages of Parkinson's disease. GDNF was infused starting 2 weeks after an intrastriatal 6-hydroxydopamine (6-OHDA) lesion in order to halt the ongoing degeneration of the nigrostriatal dopaminergic neurons. GDNF or vehicle was infused in the striatum or the lateral ventricle via an osmotic minipump over a total 4-week period (2-6 weeks postlesion). Motor function was evaluated by the stepping, paw reaching and drug-induced motor asymmetry tests before the pump infusion was initiated, and was repeated once during (5 weeks postlesion) and twice after the withdrawal of the minipumps (7 and 11 weeks postlesion). We found that within two weeks following the lesion approximately 40% of the nigral TH-positive neurons were lost. In the vehicle infusion groups there was an additional 20% cell loss between 2 and 12 weeks after the lesion. This latter cell loss occurred mainly in the caudal part of the SN whereas the cell loss in the rostral SN was almost complete within the first two weeks. Ventricular GDNF infusion completely blocked the late degenerating neurons in the caudal SN and had long lasting behavioural effects on the stepping test and amphetamine rotation, extending to 6 weeks after withdrawal of the factor. Striatal infusion affected the motor behaviour transiently during the infusion period but the motor performance of these animals returned to baseline upon cessation of the GDNF delivery, and the delayed nigral cell loss was marginally affected. We conclude that intraventricular GDNF can successfully block the already initiated degenerative process in the substantia nigra, and that the effects achieved via the striatal route, when GDNF is given acutely after the lesion, diminish as the fibre terminal degeneration proceeds.

Amphetamine↗

Effect of 2,4,6-trinitrobenzenesulphonic acid (TNBS)-induced ileitis on the motor function of non-inflamed rat gastric fundus.

During intestinal inflammation, motility disturbances are not restricted to inflamed regions, but may also occur in remote non-inflamed sites of the gastrointestinal tract. Our aim was to investigate the motor function of the gastric fundus after the induction of terminal ileitis in the rat. Ileal inflammation was induced by intraluminal installation of 2,4,6-trinitrobenzenesulphonic acid (TNBS) into the ileum. Inflammation was assessed both histologically and biochemically. Contractions and relaxations of longitudinal muscle strips from the gastric fundus were studied 36 h and 1 week later. During the acute phase of ileal inflammation (36 h), the non-inflamed stomach was distended. The contractility of longitudinal muscle strips of the gastric fundus was decreased due to a post-receptor defect. In addition, nonadrenergic noncholinergic (NANC) relaxations were inhibited due to neuronal dysfunction. Aortic contractility remained normal and the mere presence of food in the stomach did not account for the disturbed neuromuscular function in the gastric fundus. Ablation of extrinsic primary afferent neurones by capsaicin further impaired gastric fundus contractility. Transection and re-anastomosis of the jejunum reversed the effect of TNBS-induced ileitis on the neuromuscular function of the gastric fundus. One week after TNBS, cholinergic neurotransmission was increased in the gastric fundus. During acute ileitis, smooth muscle cell contractility and inhibitory NANC neurotransmission are inhibited in the non-inflamed gastric fundus. This phenomenon may be mediated by intrinsic connections within the enteric nervous system.

Animals↗

Esophageal motor function evaluated by scintigraphy, video-radiography and manometry in diabetic patients.

Prolonged esophageal scintigraphic transit time is frequent in diabetic patients and is related to autonomic neuropathy. In this study, esophageal scintigraphic transit time was correlated to esophageal motor function as evaluated by video-radiography and manometry in 13 diabetic patients. An abnormal scintigraphic transit time (greater than 15 s) occurred in 6 patients. All patients with abnormal transit time showed abnormal results at video-radiography (n = 4) and/or manometry (n = 5), which were observed in only 2 of 7 patients with normal transit time (both with abnormal video-radiography and manometry). A prolonged scintigraphic transit appears reliable as an indicator of disturbed esophageal smooth muscle function since it is well correlated with abnormalities shown by a combination of video-radiography and manometry.

Adult↗

[An automated system for evaluation of gastric motor function in duodenal ulcer].

The researchers of the Department of Medical and Biological Cybernetics and Hospital Surgery Department No. 2 of the Russian State Medical University have developed the first stage of an automatic diagnostic system to evaluate gastroduodenal motor function by intracavitary multichannel manometry. The system makes diagnostic syndromal conclusions by using an expert approach and statistic data analysis. The percentage of correct diagnoses was 92 and 80%, respectively. The system may be useful at multidisciplinary hospitals, diagnostic centers, and specialized gastroenterological care facilities.

Data Interpretation, Statistical↗

Responsiveness and uniqueness of the pediatric outcomes data collection instrument compared to the gross motor function measure for measuring orthopaedic and neurosurgical outcomes in cerebral palsy.

The Pediatrics Outcomes Data Collection Instrument (PODCI) is a valid and reliable measure of functional health status in children with acute and chronic musculoskeletal disorders, including cerebral palsy (CP), but its responsiveness has not been documented specifically for this population. The Gross Motor Function Measure (GMFM) and the Pediatric Evaluation of Disability Inventory (PEDI) are the only two instruments validated specifically as evaluative measures for CP, and while widely used, they are limited by a ceiling effect when assessing higher-functioning children. The PEDI is further restricted to children who are 7 years old or less. The goal of this study was to evaluate the responsiveness, and secondarily the uniqueness, of the PODCI compared with the GMFM for evaluating surgical outcomes in CP. Changes in the GMFM and PODCI Parent forms were assessed at two time points in 64 children with spastic CP who underwent muscle-tendon lengthenings (MT; n = 22) or neurosurgical spasticity reduction consisting of either selective dorsal rhizotomy (SDR; n = 18) or intrathecal baclofen pump implantation (ITB; n = 11) or who had no surgery between assessments (n = 13). The GMFM Total score was responsive to change after both MT surgery and SDR, with a nearly equivalent magnitude of change in both groups. However, the PODCI Global Function Scale was responsive to changes only after MT surgery, with improvement in the Sports and Physical Function subscale particularly prominent. No significant changes were noted in the ITB group for either measure.

Adolescent↗

Functional electrostimulation of muscles as a method for restoring motor functions.

The main functions of a method of functional electrical stimulation of muscles (FES) are described: diagnostic, prognostic, and therapeutic. The main indication for using the FES method is a deficiency of muscle function, which may be organic (due to lesions to neuromuscular structures) or functional (associated with relaxation of the muscular apparatus). The five most significant functions of the FES method were established: 1) identification of correctable movements and stimulable muscles; 2) identification of the amplitude and time program for stimulation; 3) stimulation regimes for pathological gaits; 4) stimulation parameters; 5) positioning of skin electrodes on the human body. Using the example of two severe central nervous system pathologies (spinal cord lesions in the lumbosacral area and hemiparesis of cerebral origin), the positive effects of FES on the process of motor rehabilitation of this category of patients were demonstrated.

Adult↗

Effects of cyclosporin-A on immune response, tissue protection and motor function of rats subjected to spinal cord injury.

The aim of this work was to test the effect of cyclosporin-A (CsA) on some immunological, morphological and functional aspects developed after spinal cord injury. The specific cellular immune response against spinal cord constituents, the amount of spared tissue and myelination at the site of injury, and the motor function outcome were assessed in a first series of experiments. Rats were subjected to spinal cord compression and treated with cyclosporin-A before lesion and during the entire study. A specific lymphocyte response against spinal cord antigens was found in untreated spinal cord injured rats but not in cyclosporine-A treated injured rats. A significantly better myelination index was also found in injured cyclosporin-A-treated rats, as compared to untreated animals. The amount of spared spinal cord tissue at the epicenter was not significantly different comparing CsA-treated with vehicle-treated rats. Looking for a potential therapeutic use of CsA, in a second series of experiments, rats were subjected to spinal cord contusion and treated with cyclosporin-A from 1 to 72 h after lesion. Motor recovery and red nuclei neurons survival, were evaluated, and found to be significantly better in spinal cord injured rats treated with cyclosporin-A than in injured-untreated rats. This work confirms the existence of an autoimmune cellular reaction after injury that can be inhibited by cyclosporin-A treatment. Furthermore, cyclosporin-A promotes neuroprotection by diminishing both demyelination and neuronal cell death, resulting in a better motor outcome after spinal cord injury.

Animals↗

Esophageal and jejunal motor function after total gastrectomy and Roux-Y esophagojejunostomy.

Emptying and peristaltic activity of the esophagus and proximal jejunum were studied using scintigraphy and fluoroscopy documented on videotape in 11 patients after total gastrectomy and Roux-Y loop reconstruction. Impaired esophageal motor function, as judged by both methods, was seen in five patients who were all 50 years of age or older. This was in contrast to the findings in a group of healthy control subjects, all over 50 years of age, in whom esophageal function appeared normal on scintigraphy in five of seven. Disturbed jejunal function, as judged by radiography, was found in eight patients, whereas the emptying rate according to scintigraphy was judged normal in all but two patients. Five of the patients complained of various adverse alimentary tract symptoms, but the scintigraphic and radiographic findings did not correlate with these symptoms.

Adult↗

[Effect of prolonged epidural morphine block on the recovery of intestinal motor function postoperatively].

The dynamics of recovery of the motor-evacuatory function of the gastrointestinal tract after operation on organs of the abdominal cavity was studied in 102 patients. Prolonged epidural blockade with subnarcotic doses of morphine was included in the complex of postoperative measures in 53 patients. Clinical observations and investigation of bioelectrical activity of the intestine have shown the prolonged epidural blockade to result in earlier recovery of the gastrointestinal function.

Adolescent↗

MEG response to median nerve stimulation correlates with recovery of sensory and motor function after stroke.

OBJECTIVE: Hemiparesis due to damage by stroke in primary motor cortex (MI) or its underlying projections presents a problem for functional neuroimaging technologies that attempt to evaluate the neurophysiological basis for restoration of motor function. Traditional assessments of MI function require patients to move their fingers, hands, or limbs, which can be either impossible or markedly compromised after stroke. We recently demonstrated in normal subjects that magnetoencephalography (MEG), a non-invasive neuromagnetic functional imaging technique, detects neuronal response elicited by electrical median nerve stimulation in MI, as well as primary somatosensory cortex (SI). In the present study, we used the MEG response from median nerve stimulation to investigate the recovery of primary motor and somatosensory in acute ischemic stroke patients. METHODS: Twelve patients with unilateral ischemic strokes that affected sensorimotor functions of their hand were studied in the acute stage (4.4+/-1.2 days, mean+/-SD) and during a 1-month follow-up (38.6+/-5.6 days, except for one patient's follow-up done 6 month after stroke). RESULTS: Among the multiple cortical sources localized after median nerve stimulation, one source localized to SI and another localized to the vicinity of MI. Changes in the source strengths of the first component post-stimulus of MI and SI correlated with the extent of recovery of sensorimotor functions as determined by neurological exams. CONCLUSIONS: This study provides a novel way of indirectly assessing MI function using MEG during the acute stroke phase, when many patients often cannot perform motor tasks due to paralysis.

Adult↗

Dystrophin-like immunoreactivity in monkey and human brain areas involved in learning and motor functions.

Two antidystrophin antibodies against different fragments of dystrophin were used to detect this polypeptide in monkey and human brains. Dystrophin was revealed by immunoperoxidase amplified with the biotin/avidin system and by immunoblotting. A dystrophin-like immunoreactivity was uniformly expressed in several brain regions implicated in learning and motor functions. Dystrophin function is not clear but our results raise the possibility that this protein may be involved in the cognitive impairment observed in several Duchenne muscular dystrophy (DMD) patients.

Animals↗

A community-based upper-extremity group exercise program improves motor function and performance of functional activities in chronic stroke: a randomized controlled trial.

OBJECTIVE: To assess the effects of a community-based exercise program on motor recovery and functional abilities of the paretic upper extremity in persons with chronic stroke. DESIGN: Randomized controlled trial. SETTING: Rehabilitation research laboratory and a community hall. PARTICIPANTS: A sample of 63 people (> or =50y) with chronic deficits resulting from stroke (onset > or =1y). INTERVENTIONS: The arm group underwent an exercise program designed to improve upper-extremity function (1h/session, 3 sessions/wk for 19wk). The leg group underwent a lower-extremity exercise program. MAIN OUTCOME MEASURES: The Wolf Motor Function Test (WMFT), Fugl-Meyer Assessment (FMA), hand-held dynamometry (grip strength), and the Motor Activity Log. RESULTS: Multivariate analysis showed a significant group by time interaction (Wilks lambda=.726, P=.017), indicating that overall, the arm group had significantly more improvement than the leg group. Post hoc analysis demonstrated that gains in WMFT (functional ability) (P=.001) and FMA (P=.001) scores were significantly higher in the arm group. The amount of improvement was comparable to other novel treatment approaches such as constraint-induced movement therapy or robot-aided exercise training previously reported in chronic stroke. Participants with moderate arm impairment benefited more from the program. CONCLUSIONS: The pilot study showed that a community-based exercise program can improve upper-extremity function in persons with chronic stroke. This outcome justifies a larger clinical trial to further assess efficacy and cost effectiveness.

Age Factors↗

Motor function of the esophagus after caustic burn.

During the subacute and chronic phases of esophagitis due to ingestion of a caustic substance, the patient commonly displays stricture, esophageal rigidity and dysphagia. We used esophageal manometry, radiology, pH monitoring and 99mTc scintigraphy to investigate esophageal motor function in 25 children (mean age 24 +/- 7 months) with chronic esophagitis after second- and/or third-degree caustic burns. The results were compared with those for a control group of 12 children (mean age 32 +/- 19 months) under surveillance for suspected gastroesophageal reflux (GER) but for whom this pathology was later ruled out. Seventeen (68%) of the lesioned-group children showed esophageal dysfunction as revealed by monitoring of pH over a 24-hour period. Over this period, the mean percentage of time with pH below 4 was 19 +/- 10%, the mean number of reflux episodes was 48 +/- 52, the mean number of reflux episodes lasting longer than 5 min was 10 +/- 5, and the mean duration of the longest reflux episode was 51 +/- 21 min. Manometry indicated that, in the lesioned group, an average of 77 +/- 18% of peristaltic waves were nonpropulsive, while the mean Esophageal Work Index (number of propulsive waves per hour x mean maximum pressure developed during propulsive waves) was 227 +/- 192 units. All of the above means were significantly different (p < 0.01) from the corresponding control-group means. Esophageal strictures were observed in 60% (15) of the children. In 2 cases it was minimal, 2 cases moderate and 11 cases had severe strictures. 99mTc scintigraphy indicated that esophageal transit was slightly delayed in four, moderately delayed in five and severely delayed in 16 of the lesioned-group subjects. There was close correspondence between the results of manometry and scintigraphy as regards severity of esophageal dysfunction. These results indicate that motility disturbances and GER are very frequent sequelae of caustic burns of the esophagus, and should be taken into account when evaluating symptoms and deciding on the therapeutic strategy (including diet) to be followed.

Burns, Chemical↗