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PubMed2002

Uranyl acetate-induced sensorimotor deficit and increased nitric oxide generation in the central nervous system in rats.

We investigated the effects of uranyl acetate on sensorimotor behavior, generation of nitric oxide and the central cholinergic system of rats. Male Sprague-Dawley rats were treated with intramuscular injection of 0.1 and 1 mg/kg uranyl acetate in water, daily for 7 days. Control animals received equivalent amount of water. The treatment was stopped after the seventh injection because the animals in the 1-mg/kg group appeared lethargic. The animals were maintained for an additional observation period of 30 days. The study was initiated as a dose-finding study that covered doses of 10 and 100 mg/kg, as well. However, all the animals in the 100-mg/kg treatment group died after the third and fourth injections, and all animals given 10 mg/kg died after the fifth and sixth injections. On Day 30 following the cessation of treatment, the sensorimotor functions of the animals in the 0.1- and 1-mg/kg treatment groups were evaluated using a battery of tests that included measurements of postural reflexes, limb placing, orientation to vibrissae touch, grip time, beam walking and inclined plane performance. The animals were sacrificed the same day and the cerebral cortex, brainstem, cerebellum and midbrain were dissected. The levels of nitric oxide as marker for increased oxidative stress, and the integrity of the cholinergic system as reflected in acetylcholinesterase (AChE) activity and m2 muscarinic acetylcholine receptors ligand binding, were determined. The data from behavioral observations show that there was a dose-related deficit at the 0.1- and 1-mg/kg treatment groups for inclined plane performance. Both doses reduced grip time, but there was no significant difference between the two doses. Similarly, both beam-walk score and beam-walk time were impaired at both doses as compared with the controls. A significant increase in nitric oxide was seen at 0.1 mg/kg dose in cortex and midbrain, whereas brainstem and cerebellum showed an insignificant decrease at both the doses. Similarly, there was no significant change in nitric oxide levels in kidneys and liver of the treated animals as compared with the controls. There was a significant increase in AChE activity in the cortex of the animals treated with 1 mg/kg uranyl acetate, but not in other brain regions. Ligand binding densities for the m2 muscarinic receptor did not show any change. These results show that low-dose, multiple exposure to uranyl acetate caused prolonged neurobehavioral deficits after the initial exposure has ceased.

Acetylcholinesterase↗
PubMed1997

A new trend in the study of low back pain in workplaces.

In 1996, the number of low back pain (LBP) cases totaled 5,162 in Japan, accounting for 60% of the total number of officially recognized cases of occupational diseases. In recent decades, the number of LBP cases, however, has been gradually decreasing. The rate of this decrease is slower in non-manufacturing industries than in other sectors, while the prevalence rate of LBP has tended to increase among workers in tertiary industries in 1995 and 1996. Epidemiological studies have clarified that workplace factors of LBP include not only the handling of heavy materials, but also unnatural postures, sudden and unexpected motions, and individual worker's characteristics. It was, therefore, suggested that comprehensive countermeasures to prevent LBP be undertaken on the basis of work environmental control, work management practice, and health care. The Labor Ministry of Japan issued guidelines for the prevention of LBP in 1994, in which various factors in the work environment, the importance of readiness for motion, standardization of work procedures, and exercise before work were newly outlined. In addition to the psychophysical and biomechanical models of LBP so far reported, established findings of physiological studies on muscle tone and postural reflexes have been conceptually introduced into the guidelines. Such physiological findings are essential for the mechanistic elucidation of work-related LBP and the preparation of its countermeasures, as LBP can also be caused by sudden and unexpected motions as well as various environmental factors. Physical and mental readiness to cope with changes in voluntary motions is a prerequisite for the prevention of LBP in daily work, which constitutes time-sequential changes in posture and motion under various environmental conditions. This paper critically reviews the workplace factors of LBP, its models for evaluating the workload on the body, and environmental risk factors with reference to the neural control of muscle contraction underlying the voluntary motion of workers.

Biomechanical Phenomena↗
PubMed1998

Role of gravity in the development of posture and locomotion in the neonatal rat.

This report describes the early motor behaviour in the neonatal rat in relation with the maturation of sensory and motor elements of the central nervous system (CNS). The role of vestibular information during the week before (E14-21) and the 2 weeks after (P0-15) birth will be considered. There is a rostro-caudal gradient in the maturation of posture and locomotion with a control of the head and forelimbs during the first postnatal week and then a sudden acceleration in the functional maturation of the hindlimb. At birth, the neonatal rat is blinded and deaf; despite the immaturity of the other sensory systems, the animal uses its olfactory system to find the mother nipple. Vestibular development takes place between E8 and P15. Most descending pathways from the brainstem start to reach the lumbar enlargement of the spinal cord a few days before birth (reticulo-, vestibulospinal pathways as well as the serotonergic and noradrenergic projections); their development is not completed until the end of the second postnatal week. At birth, in an in vitro preparation, a locomotor activity can be evoked by perfusing excitatory amino acids and serotonin over the lumbar region. The descending pathways which trigger the activity of the CPG are also partly functional. At the same age both air stepping and swimming can be induced. Complex locomotion such as walking, trotting and galloping start later because it requires the maturation of the vestibular system, descending pathways and postural reflex regulation. The period around birth is critical to properly define how the vestibular information is essential for the structuring of the motor behaviour. Different types of experiments (hypergravity, microgravity) are planned to test this hypothesis.

Aging↗
PubMed1985

Plasma epinephrine concentration in healthy men: correlation with systolic pressure and rate-pressure product.

Relations among plasma epinephrine, norepinephrine and renin activity and systolic pressure, diastolic pressure, heart rate and the product of heart rate and systolic pressure (rate-pressure product) were evaluated in 31 healthy men whose arterial pressure spanned the range from normal to mildly elevated. Measurements were made during 60 minutes with the patient in the supine position and during 10 minutes of quiet standing. In the supine position, highly significant regressions were found between systolic pressure or rate-pressure product and plasma epinephrine, but not between these variables and norepinephrine or renin activity. A weakly significant correlation was also found between heart rate and norepinephrine. On standing, norepinephrine and epinephrine increased significantly. In this position, rate-pressure product was significantly related by regression analysis only with plasma epinephrine. Weakly significant correlations between systolic pressure and epinephrine and between heart rate and norepinephrine and epinephrine were also found. Plasma renin activity was not significantly correlated with arterial pressure, heart rate or rate-pressure product in either position. These results suggest that plasma epinephrine is a determinant of systolic pressure when postural reflexes are minimized and that epinephrine may participate in control of cardiac work load, as reflected by rate-pressure product in the absence of exercise or definable stress.

Adolescent↗
PubMed1990

A basic posture control mechanism: the stabilization of the centre of gravity.

Holding the body's centre of gravity steady represents the crucial variable for the stabilization of posture in upright stance in man. The visual, vestibular and muscle proprioceptive systems have all been shown to contribute to sway stabilization. Nevertheless, earlier work has suggested that an additional receptor system is needed to signal the position of the body's centre of gravity relative to the support surface, i.e., the feet. This proposed receptor system should be 'gravity' dependent. To evaluate the properties of this receptor system, an experiment was designed under simulated 'microgravity', in water immersion. An approximately linear relationship was found between contact force and impulse directed EMG response amplitudes in the leg muscles. Out of water loading of the subjects resulted in no further increase of the response amplitude. A gain control mechanism for postural reflexes which is dependent on body weight was demonstrated. In a further experiment it could be shown that the receptors for this mechanism are distributed along the vertical axis of the body: it is suggested that these force-dependent receptors are pressure receptors within the joints and the vertebral column.

Adult↗
PubMed2005

The cerebellum may implement the appropriate coupling of sensory inputs and motor responses: evidence from vestibular physiology.

Starting from a survey of current ideas on the role of the cerebellum in sensorimotor transformations, the present review summarizes the results of recent experiments showing that (a) somatosensory signals modify the spatial organization of the postural reflexes, thus leading to body stability, and (b) otolith input changes the plane of reflex eye movements, by keeping it perpendicular to the gravito-inertial vector. Evidence will be given that both transformations require the integrity of specific cerebellar regions. These data indicates that the cerebellum allows an optimal input-output coupling in relation to the ultimate behavioural goal of the motor activity.

Animals↗
PubMed1982

The origin of left hand preference: pathological and non-pathological influences.

Models of the origin of left hand preference were tested with prospective data. Infants with and without a history of perinatal complications, matched for age, sex and parental handedness, were filmed at 6 weeks of age. Children with a history of perinatal complications lacked the rightward headturning bias of those children without a history of perinatal trauma. Children with a history of perinatal complications were also deviant with reference to the duration of a postural reflex and its degree of lateralization. Perinatal complications may delay the establishment of volitional hand use as well as increase the probability of left-handedness. The data were interpreted as supporting SATZ's (Cortex 8, 121-135, 1972) rather than BAKAN et al.'s (Neuropsychologia 11, 363-366, 1973) model of "pathological" left-handedness.

Birth Injuries↗
PubMed1995

Control of locomotion in marine mollusk Clione Limacina. IX. Neuronal mechanisms of spatial orientation.

1. When swimming freely, the pteropod mollusk Clione limacina actively maintains a vertical orientation, with its head up. Any deflection from the vertical position causes a correcting motor response, i.e., bending of the tail in the opposite direction, and an additional activation of the locomotor system. Clione can stabilize not only the vertical orientation with its head up, but also the posture with its head down. The latter is observed at higher water temperature, as well as at a certain stage of hunting behavior. The postural control is absent in some forms of behavior (vertical migrations, defensive reactions, "looping" when hunting). The postural reflexes are driven by input from the statocysts. After removal of the statocysts, Clione was unable to maintain any definite spatial orientation. 2. Activity of the neuronal mechanisms controlling spatial orientation of Clione was studied in in vitro experiments, with the use of a preparation consisting of the CNS and statocysts. Natural stimulation (tilt of the preparation up to 90 degrees) was used to characterize responses in the statocyst receptor cells (SRCs). It was found that the SRCs depolarized and fired (10-20 Hz) when, during a tilt, they were in a position on the bottom part of the statocyst, under the statolith. Intracellular staining has shown that the SRC axons terminate in the medial area of the cerebral ganglia. Electrical connections have been found between some of the symmetrical SRCs of the left and right statocysts. 3. Gravistatic reflexes were studied by using both natural stimulation (tilt of the preparation) and electrical stimulation of SRCs. The reflex consisted of three components: 1) activation of the locomotor rhythm generator located in the pedal ganglia; this effect of SRCs is mediated by previously identified CPA1 and CPB1 interneurons that are located in the cerebral ganglia and send axons to the pedal ganglia; 2) bending the tail evoked by differential excitation and inhibition of different groups of tail muscle motor neurons; this effect is mediated by CPB3 interneurons; and 3) modification of wing movements by differential excitation and inhibition of different groups of wing motor neurons; this effect is mediated by CPB2 interneurons. 4. Gravistatic reflexes in the tail motor neurons were inhibited or reversed at a higher water temperature. 5. The SRCs are not "pure" gravitation sensory organs because they are subjected to strong influences from the CNS. In particular, CPC1 interneurons, participating in coordination of different aspects of the hunting behavior, exert an excitatory action on some of the SRCs, and inhibitory actions on others.(ABSTRACT TRUNCATED AT 400 WORDS)

Animals↗
PubMed1989

Plasma norepinephrine in Chagas' cardioneuromyopathy: a marker of progressive dysautonomia.

Chronic Chagas' disease produces pathologic changes of the cardiovascular, digestive, and autonomic nervous systems. In an attempt to elucidate the nature of the dysautonomia in patients with Chagas' disease, we measured plasma norepinephrine levels, blood pressure, and heart rate, both supine and standing in 26 patients, and compared these values of patients classified according to three clinical subsets of cardiovascular manifestations with the values of nine normal volunteers and 16 patients with nonchagasic heart failure. Results suggested (1) progressive blockade of the alpha receptor in patients with Chagas' disease who have minimal clinical symptoms (group I) and in those who have ECG alterations without congestive symptoms (group II), as reflected by normal or raised plasma norepinephrine levels without change of diastolic blood pressure during standing, which indicates absent postural reflexes; and (2) blockade associated with partial denervation in patients with Chagas' disease who have class III or IV heart failure (group III), as suggested by a lower supine plasma norepinephrine level and a fall in diastolic blood pressure in the upright position. The findings of reduced plasma norepinephrine levels are in contrast to the elevated plasma norepinephrine levels in patients without Chagas' disease with class III and IV heart failure who have sympathetic hyperactivity.

Adult↗
PubMed1986

Individual manifestations of Parkinson's disease after ten or more years of levodopa.

Twenty-five consecutive patients with Parkinson's disease, who had been on levodopa for 10 or more years, were studied. Over the 12.9 years of treatment, the average Northwestern Disability Score had increased from 9.6 to 18.9. By this measure, 24 of 25 patients were worse, and one was unchanged. The progression of disability did not involve all pretreatment parkinsonian features equally in any of the patients studied. Instead a distinctive pattern of deterioration was seen: postural reflexes worsened in 24/25, speech in 24/25, and gait in 22/25. In contrast, rigidity was improved or unchanged in 17/25, tremor was improved or unchanged in 17/17, while handwriting was improved or unchanged in 21/22. Finger dexterity which was improved in 5/25, unchanged in 15/25, and worse in 5/25 which seemed to be between these two extremes. These observations demonstrate that some signs of parkinsonism can remain quite responsive to levodopa for more than 10 years while at the same time other manifestations of the disease are no longer as responsive to this form of treatment.

Gait↗
PubMed1999

Extrapyramidal involvement in amyotrophic lateral sclerosis: backward falls and retropulsion.

Three patients with sporadic amyotrophic lateral sclerosis (ALS) presented with a history of backward falls. Impaired postural reflexes and retropulsion accompanied clinical features of ALS. Hypokinesia, decreased arm swing, and a positive glabellar tap were noted in two of these three patients. Cognitive impairment, tremor, axial rigidity, sphincter dysfunction, nuchal dystonia, dysautonomia, and oculomotor dysfunction were absent. Brain MRI disclosed bilateral T2 weighted hyperintensities in the internal capsule and globus pallidus in one patient. Necropsy studies performed late in the course of ALS have shown degeneration in extrapyramidal sites-for example, the globus pallidus, thalamus, and substantia nigra. Clinically, backward falls and retropulsion may occur early in ALS. This may reflect extrapyramidal involvement.

Aged↗
PubMed1975

A three-phase clinical evaluation of prazosin.

A preliminary study of cardiac hemodynamics with measurement in both supine and tilt positions showed that the antihypertensive effect of prazosin given intravenously is associated with a fall in total peripheral resistance, with minor effects on cardiac output and heart rate, and with no consistent orthostatic hypotension. The postural reflexes appear to remain intact. The results are entirely similar to those reported by Lund-Johansen. In a second, short-term study of ambulatory patients, prazosin alone exerted an antihypertensive effect somewhat less than that of methyldopa, but the difference in blood pressure reduction between supine and standing positions was less with prazosin than with methyldopa. Both drugs were well tolerated. In a third, long-term study, prazosin alone gave satisfactory antihypertensive results, and prazosin used in combination with polythiazide produced a satisfactory response in 80% of the patients.

Adult↗
PubMed1999

Integration of vestibular and head movement signals in the vestibular nuclei during whole-body rotation.

Single-unit recordings were obtained from 107 horizontal semicircular canal-related central vestibular neurons in three alert squirrel monkeys during passive sinusoidal whole-body rotation (WBR) while the head was free to move in the yaw plane (2.3 Hz, 20 degrees /s). Most of the units were identified as secondary vestibular neurons by electrical stimulation of the ipsilateral vestibular nerve (61/80 tested). Both non-eye-movement (n = 52) and eye-movement-related (n = 55) units were studied. Unit responses recorded when the head was free to move were compared with responses recorded when the head was restrained from moving. WBR in the absence of a visual target evoked a compensatory vestibulocollic reflex (VCR) that effectively reduced the head velocity in space by an average of 33 +/- 14%. In 73 units, the compensatory head movements were sufficiently large to permit the effect of the VCR on vestibular signal processing to be assessed quantitatively. The VCR affected the rotational responses of different vestibular neurons in different ways. Approximately one-half of the units (34/73, 47%) had responses that decreased as head velocity decreased. However, the responses of many other units (24/73) showed little change. These cells had signals that were better correlated with trunk velocity than with head velocity. The remaining units had responses that were significantly larger (15/73, 21%) when the VCR produced a decrease in head velocity. Eye-movement-related units tended to have rotational responses that were correlated with head velocity. On the other hand, non-eye-movement units tended to have rotational responses that were better correlated with trunk velocity. We conclude that sensory vestibular signals are transformed from head-in-space coordinates to trunk-in-space coordinates on many secondary vestibular neurons in the vestibular nuclei by the addition of inputs related to head rotation on the trunk. This coordinate transformation is presumably important for controlling postural reflexes and constructing a central percept of body orientation and movement in space.

Animals↗
PubMed1998

Fetal spinal cord transplants support growth of supraspinal and segmental projections after cervical spinal cord hemisection in the neonatal rat.

Cervical spinal cord injury at birth permanently disrupts forelimb function in goal-directed reaching. Transplants of fetal spinal cord tissue permit the development of skilled forelimb use and associated postural adjustments (, companion article). The aim of this study was to determine whether transplants of fetal spinal cord tissue support the remodeling of supraspinal and segmental pathways that may underlie recovery of postural reflexes and forelimb movements. Although brainstem-spinal and segmental projections to the cervical spinal cord are present at birth, skilled forelimb reaching has not yet developed. Three-day-old rats received a cervical spinal cord overhemisection with or without transplantation of fetal spinal cord tissue (embryonic day 14); unoperated pups served as normal controls. Neuroanatomical tracing techniques were used to examine the organization of CNS pathways that may influence target-directed reaching. In animals with hemisections only, corticospinal, brainstem-spinal, and dorsal root projections within the spinal cord were decreased in number and extent. In contrast, animals receiving hemisections plus transplants exhibited growth of these projections throughout the transplant and over long distances within the host spinal cord caudal to the transplant. Raphespinal axons were apposed to numerous propriospinal neurons in control and transplant animals; these associations were greatly reduced in the lesion-only animals. These observations suggest that after neonatal cervical spinal cord injury, embryonic transplants support axonal growth of CNS pathways and specifically supraspinal input to propriospinal neurons. We suggest that after neonatal spinal injury in the rat, the transplant-mediated reestablishment of supraspinal input to spinal circuitry is the mechanism underlying the development of target-directed reaching and associated postural adjustments.

Animals↗
PubMed2001

Freezing of gait in patients with advanced Parkinson's disease.

BACKGROUND: Freezing of Gait (FOG) is one of the most disturbing and least understood symptom in advanced stage of Parkinson's disease (PD). The contribution of the underlying pathological process and the antiparkinsonian treatment to the development of FOG are controversial. OBJECTIVE: To study the relationships between clinical features of PD and therapeutic modalities in patients with advanced PD and FOG. METHODS: Consecutive patients with 5 years or more of PD symptoms (n = 172) (99 men) with mean age at symptoms onset of 58.3 +/- 13.2 years and mean symptoms duration of 11.8 +/- 5.6 years were studied. Clinical data were collected during the last office visit through physical examination, detailed history, review of patients' charts, and other documents. A patient was considered as "freezer" if he/she reported recent experience that the legs got stuck to the ground while trying to walk. The presence of dyskinesia, early morning dystonia or significant postural reflex abnormalities were assessed through history and neurological examination. Duration of treatment with antiparkinsonian drugs was calculated from history charts. Chi square and t test were used to compare the patients with and without FOG. Logistic regression was used for the comparison of association between the presence of FOG (dependent variable) disease duration and disease stage (explanatory variables) and duration of treatment with anti-parkinsonian drugs. RESULTS: The study population consisted of 45 patients at Hoehn and Yahr (H&Y) stage 2.5 (26%), 104 patients at stage 3 (60.5%), and 23 patients at H&Y stages 4-5 (13.5%). Ninety one patients (53%) reported FOG at the time of the study. Severity of the disease expressed by H&Y stage at "off" was a significant contributing factor for FOG with a significant trend (z = 4.38, p < 0.0001), as was longer duration of levodopa treatment, and confirmed by FOG using the multivariate logistic regression (p = 0.01 and p = 0.004, respectively). Using a univariate model, longer duration of treatment with dopamine agonists contribute to the appearance of FOG (p = 0.07) while longer duration of amantadine treatment decreased the appearance of FOG (p = 0.09). There was a significant association between FOG and the presence of dyskinesia (p < 0.002), early morning foot dystonia (p < 0.003) and significant postural instability (p < 0.0005). CONCLUSION: FOG is a common symptom in advanced PD. It is mainly related to disease progression and levodopa treatment.

Adult↗
PubMed1988

Spared-root deafferentation of a cat's hindlimb: hierarchical regulation of pathways mediating recovery of motor behavior.

Previous studies showed that after complete hindlimb deafferentation in cats, the ipsilateral descending pathways mediated recovery of overground, goal-directed locomotion and accurate placement of the deafferented limb. In the present study deafferentations sparing one dorsal root (L6) were performed to see if the descending systems would still be responsible for the recovery. The partially deafferented hindlimb is initially impaired in postural reflexes and accurate placement during locomotion but considerable recovery occurs. A similar pattern of severe impairment and subsequent recovery is observed in cats in which the only lesion is L1 hemisection. When a hemisection is added 6 months later to chronic spared-root deafferentation the recovery (from the latter lesion) is temporarily reversed but the animals recover again in a fashion similar to that after hemisection alone. Since there is no recovery of overground locomotion when hemisection is added to complete deafferentation but there is when deafferentation is incomplete, the descending pathways apparently are not responsible for maintaining the recovery when one dorsal root is spared as they are when all are cut. The results suggest that a competitive or hierarchical control over residual systems may regulate recovery of motor function.

Animals↗
PubMed1994

Recovery of sensorimotor function after distal middle cerebral artery photothrombotic occlusion in rats.

BACKGROUND AND PURPOSE: The purpose of the present study was to delineate the behavioral correlates of focal thrombotic occlusion of the distal middle cerebral artery in rats and to compare the pattern of deficits and subsequent recovery to that following proximal middle cerebral artery occlusion. METHODS: Ten Sprague-Dawley rats underwent photothrombotic occlusion of the distal middle cerebral artery with tandem occlusion of the common carotid arteries (dMCAO group); 10 animals served as operated controls. Beginning on postischemia day 2, animals were given a battery of five tests that assessed sensorimotor integration, attentional mechanisms, and muscle strength; testing continued twice weekly until day 30. Nine days of cognitive testing on the learning set of the water maze task were then given. Infarct volume and hemispheric atrophy were determined for each dMCAO animal. RESULTS: After ischemia, the dMCAO group exhibited significant behavioral deficits in posture reflex, ability to place a forelimb to various stimuli, limb adduction during rearing, and neglect of contralateral space. These deficits showed variable recovery rates. No deficits were observed in muscle strength or cognitive performance. The deficits and patterns of recovery were related to infarct location and to degree of hemisphere atrophy. CONCLUSIONS: The present study suggests that a battery of tests is necessary to fully characterize the pattern of behavioral deficits after focal cerebral ischemia. Location of infarct damage and associated degree of hemispheric atrophy were important variables in determining behavioral outcome. The present results are compared with those of the more traditional model of electrocoagulation of the proximal middle cerebral artery.

Animals↗
PubMed1989

Long-term neurological assessment of the post-resuscitative effects of flunarizine, verapamil and nimodipine in a new model of global complete ischaemia.

In anesthetized rats, global complete ischaemia lasting for 9 min was induced by controlled hydraulic compression of the chest. A neurological score, based on cranial and spinal reflexes, postural tone, gait, movement and limb placement, was determined at 2 hr and 1, 2, 3, 7, 14, 21 and 28 days after resuscitation. Three doses of three calcium antagonists, flunarizine, verapamil and nimodipine and their respective solvents, were given intravenously during the resuscitation. The total neurological score was significantly better than solvent with 0.16 and 0.63 mg/kg of flunarizine and 0.04 and 0.16 mg/kg of verapamil; it was significantly better with solvent (10% ethanol) than with 0.04 and 0.16 mg/kg of nimodipine. The deficiency in tactile placing reactions of the hindpaws was the most resistant to therapy. This non-invasive model of global ischaemia in rats seems useful for the evaluation of drugs, since it requires minimal anesthesia and allows assessment of neurological recovery over an extended period of time.

Anesthesia↗