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Effects of graft placement site on the survival of adrenal medulla transplants into the brain and its relation with the recovery of motor function.

BACKGROUND: Because of their lack of long-term viability, adrenal tissue transplants have shown limited success in alleviating the motor disturbances associated with experimental and pathologic striatal dopamine denervation. In this study, we examined how the graft placement site influences adrenal medulla transplant survival and its relation with the reduction of motor deficits in rats bearing unilateral 6-OHDA lesion. METHODS: One or 5 microL of fetal adrenal medullar tissue was grafted either inside the striatal parenchyma or into the lateral ventricle in contact with the dopamine-denervated striatum. Motor disturbances, as assessed by apomorphine-induced rotation, were correlated to the graft morphologic survival features. RESULTS: Apomorphine-induced rotation showed a marginal reduction of 11% in all groups independently of graft survival features or placement site. Intrastriatal transplants showed limited viability characterized by a substantial loss of graft initial volume as well as fewer and smaller chromaffin cells compared to ventricular grafts, which had a reduced loss of graft initial volume and more and larger chromaffin cells. CONCLUSIONS: Although the lateral ventricle may favor adrenal medulla transplant viability, their induced motor outcome is comparable to that induced by less viable intrastriatal grafts, suggesting that the implanted dopamine-producing cells may interact and influence striatal neurons better when placed in close proximity.

Adrenal Medulla↗

Tests of motor function in patients suspected of having mild unilateral cerebral lesions.

OBJECTIVE: Though various textbooks describe clinical manoeuvres that help detect subtle motor deficits, their sensitivity, specificity and predictive values have not been determined. We investigated the sensitivity, specificity and predictive values of various manoeuvres in order to determine the most sensitive and reliable test or combination thereof. METHODS: Straight arm raising (Barré), pronator drift, Mingazzini's manoeuvre, finger tap, forearm roll, segmental strength and deep tendon reflexes were tested in 170 patients with (86) and without (84) a proven lesion in the motor areas confirmed by computed tomography. RESULTS: Segmental motor strength bad good specificity (97.5%) but poor sensitivity (38.9%) and negative predictive value (NPV) (58.7%). The forearm roll had a similar profile. Finger tap had a sensitivity of 73.3% and a specificity of 87.5%. Barré and pronator testing had a sensitivity and specificity of 92.2% and 90.0% respectively. Hyperreflexia had a sensitivity of 68.9% and a specificity of 87.5%. An abnormality of pronator, reflexes or finger tap had a sensitivity of 97%, and when these three tests were positive, specificity was 97%. When all six tests were positive, the positive predictive value was 100%, when all six tests were negative the NPV was 100%. CONCLUSION: The detailed segmental examination has very good specificity for detecting motor deficits, but the sensitivity and NPV are unacceptably low. Pronator drift with finger tap and reflexes is the most reliable and time-effective combination of tests for the detection of subtle motor lesions, and could replace the segmental motor examination as a screening for motor lesions.

Brain Diseases↗

Effects of a three-year exercise program on motor function and cognitive processing speed in older women.

This study evaluated the effects of a three-year exercise program on motor performance and cognitive processing speed of previously sedentary older women, ages 57-85. Variables tested were simple and choice reaction time (CRT), balance, sit and reach flexibility, shoulder flexibility, and grip strength. Subjects participated three times a week in exercise performance classes designed to meet American College of Sports Medicine guidelines. Results indicate that performance was significantly improved on all measures during the course of the study (p less than .01) except for the sit and reach test (SRT), where significance was approached (p less than .027), but not reached. A comparison of the exercise subjects with a comparable group of nonexercising control subjects revealed significant interactions between treatment and time on all variables except CRT and grip strength. Pretest to posttest scores of the exercise subjects tended to improve over the three-year period, whereas the scores of the control subjects declined. Improved reaction time indicated exercise is effective in reversing or at least slowing ceratin age-related declines in motor performance and in speed of cognitive processing.

Aged↗

Functional motor microdomains of the outer hair cell lateral membrane.

The outer hair cell (OHC) of the mammalian inner ear is a highly partitioned neuroepithelial cell whose lateral membrane is devoted to electromotility, a fast mechanical length change owing to the motor protein, prestin. Spatially restricted measures of prestin-derived nonlinear capacitance or gating charge, using either electrical amputation or discrete membrane mechanical deformation, were used to determine that functional variation exists within the extensive lateral membrane of the cell. This was evidenced by variation in the motor's operating voltage range and sensitivity among microdomains within the lateral membrane. That is, localized regions of the membrane evidenced Boltzmann distributions of motor charge whose midpoint voltage and slope differed from those obtained for the whole cell. These data highlight the functional independence of microdomains and imply that measured whole cell characteristics may differ from the microscopic characteristics of elementary motors.

Animals↗

The effect of chronic L-dopa treatment on the recovery of motor function in 6-hydroxydopamine-lesioned rats receiving ventral mesencephalic grafts.

The effect of treatment for 5 weeks with L-DOPA (200 mg/kg/24 h) plus carbidopa (25 mg/kg/24 h) on the behavioral recovery produced by rat fetal ventral mesencephalon grafts implanted into the striatum of 6-hydroxydopamine-lesioned rats was assessed. Animals with unilateral 6-hydroxydopamine lesions of the nigrostriatal pathway and a sham graft (Group A) showed persistent high rates of rotation in response to the administration of apomorphine (0.5 mg/kg, s.c.) (contralateral rotation) or (+)-amphetamine (5 mg/kg, i.p.) (ipsilateral rotation). Treatment of sham-grafted animals with L-DOPA plus carbidopa had no effect on the rate of rotation to apomorphine or (+)-amphetamine (Group B). The proportion of animals showing marked stereotypy following apomorphine administration was greater in sham-grafted animals receiving L-DOPA and carbidopa than in sham-grafted animals alone. Animals receiving unilateral 6-hydroxydopamine lesions followed by a fetal graft (Group C) showed a reduction in apomorphine-induced contralateral rotation and a complete reversal of (+)-amphetamine-induced ipsilateral rotation when assessed 6 weeks later. The reductions in apomorphine- and (+)-amphetamine-induced rotational behaviour produced by the fetal graft in animals with a 6-hydroxydopamine lesion were not altered by treatment with L-DOPA plus carbidopa (Group D). The proportion of animals showing marked apomorphine-induced stereotypy did not change significantly in either group over time. In rats with a unilateral 6-hydroxydopamine lesion receiving fetal dopamine grafts, treatment with high doses of L-DOPA and carbidopa for 5 weeks does not have a detrimental effect on the functional activity of the grafts as assessed by reduction of apomorphine- and (+)-amphetamine-induced motor asymmetry. The continuation of L-DOPA therapy may not adversely affect fetal graft survival and growth in patients with Parkinson's disease.

Animals↗

TRH in therapeutic vs. nontherapeutic seizures: affective and motor functions.

We have modeled some aspects of electroconvulsive therapy (ECT) in rats. In addition to sham-treated controls, one group received two electroconvulsive (ECS) current-doses at grand mal seizure threshold. Two more groups received three additional ECSs at two higher current-doses. Only the two suprathreshold groups showed significant antidepressant (AD) effects in the forced-swim test, but all three seizure groups showed significant increases in TRH and related peptides in anterior cortex (AC), pyriform cortex (PYR), amygdala/entorhinal cortex (AY), and hippocampus (HC). In motor cortex (MC), TRH appeared to be increased only in the lower dose suprathreshold ECS condition. No condition increased TRH in striatum (STR). These results fell short of directly implicating limbic TRH in AD effects, but in HC, MC, and STR, correlations of peptide levels with individual swim scores raise the possibility that this peptidergic system might be involved in motor as well as affective functions. Other peptides related to TRH might also be implicated in affective regulation and antidepressant effects.

Affect↗

Dietary supplementation of omega-3 polyunsaturated fatty acids worsens forelimb motor function after intracerebral hemorrhage in rats.

Dietary intake of omega-3 polyunsaturated fatty acids has been associated with decreased clotting ability and increased risk of hemorrhagic stroke. The aim of the current study was to assess the effect of dietary supplementation of omega-3 polyunsaturated fatty acid on functional outcome after hemorrhagic stroke. Rats were maintained on a diet containing approximately 30% of energy as either fish oil (rich in omega-3 fatty acids) or safflower oil (rich in omega-6 fatty acids) and subjected to either intracerebral hemorrhage or sham surgery. Behavioral tests, infarct measurement, and MR imaging techniques were used to assess outcome. While there was no significant difference in infarct volume between rats on different diets, animals maintained on a diet enriched with fish oil exhibited increased cerebral blood flow after surgery. These animals were significantly more impaired than rats fed the safflower-oil-enriched diet in tests of forelimb dexterity and fine motor control. These results suggest that high intake of omega-3 polyunsaturated fatty acids may not only increase the risk of hemorrhagic stroke as shown in previous studies, but most importantly may lead to a more severe motor impairment and a poorer functional outcome after such an event.

Animals↗

Intestinal motor function in irritable bowel syndrome.

Irritable bowel syndrome is widely considered to be associated with disordered gastro-intestinal motility. The evidence for a motor disorder in the colon and small intestine of patients with irritable bowel syndrome is reviewed. Results of myoelectric, motility and transit studies in both the colon and small intestine are inconsistent. Difficulties in interpreting colonic motility have led investigators to address the small intestine as a possible site of dysmotility. An increase in the number of clustered contractions in the proximal small intestine has been reported by some, but not all investigators. Methodological differences as well as patient selection, symptom severity and fluctuation may all contribute to discrepancies between the results of different studies. Motility disturbances may be present which are currently unrecognised due to an inadequate understanding of the propagation of colonic contractions, and of small intestinal contractions during phase II and postprandially. Whether the reported motor disturbances arise locally in the gut or originate from higher centres in the central nervous system has not been established.

Colon↗

Effects of the dopamine agonist pramipexole on depression, anhedonia and motor functioning in Parkinson's disease.

Depression affects approximately 45% of all patients with Parkinson's disease, reduces quality of live independent of motor symptoms and seems to be underrated and undertreated. Pramipexole shows D(3)- versus D(2)-receptor preference at cortico-frontal dopamine receptors and neurotrophic effects which seem to relate to its antidepressant and anti-anhedonic properties in Parkinson's disease and bipolar depression found in controlled studies. In the present study, effects of pramipexole were investigated under routine clinical conditions. Anhedonia was measured in patients with Parkinson's disease (n=657) using the self-rated Snaith-Hamilton-Pleasure-Scale (SHAPS-D), depression was assessed by the observer-rated Short-Parkinson's-Evaluation Scale (SPES). Anhedonia was present in 45.7% of all patients and in 79.7% of the depressed patients with Parkinson's disease. Mild depression was present in 47%, moderate to severe depression in 22% of the patients. At the end of the study period of 9 weeks on an average, the mean dosage of pramipexole was 1.0+/-0.6 mg/d (range 0.3 to 4.2). Frequency of depression (moderate to severe: 6.8%, mild: 37.6%) and anhedonia (25.5%) as well as motor deficits were significantly reduced during treatment with pramipexole. Drop-outs due to adverse events occurred in 3.5%. Future studies should investigate specificity of anti-anhedonic and antidepressive properties of pramipexole.

Aged↗

In vitro methods for the analysis of motor function in the developing spinal cord of the chick embryo.

The isolated spinal cord of the chick embryo spontaneously generates episodes of motor activity in vitro that can be recorded from muscle nerves and ventral roots. In vitro systems provide stable conditions for intra- and extra-cellular recordings and enable pharmacological and ionic manipulations of the neuronal environment. Studies of motor activity generated by isolated spinal cord have revealed the existence of co-ordinated motor output from early in development, in which antagonist motoneurons alternate in their activity and synergists are co-active. Intra-cellular recordings from single neurons and electronic recordings from muscle nerves have provided insight into the mechanism of flexor and extensor alternation. These studies have revealed that flexor and extensor motoneurons receive a similar de-polarization during each cycle of motor activity, but that the two classes of motoneuron process the de-polarization differently. Flexors fire late in each cycle whereas extensors fire early, which leads to a pattern of alternation. The cellular mechanisms responsible for the differences in the firing behavior of flexor and extensor motoneurons are currently being investigated using techniques that are only possible using the in vitro preparation.

Animals↗