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Biomedical subjects

A Gramsbergen

Publications and source records attributed to A Gramsbergen.

At least 55 records · Page 3Linked to original sources

Changes in the electromyogram of two major hindlimb muscles during locomotor development in the rat.

The development of the electromyogram (EMG) of tibialis anterior (TA) and medial gastrocnemius (GM) during locomotion was studied in normal rats from the onset of quadruped walking (postnatal day 10, P10) until P42. The objectives were to relate signal properties of the EMG and coordination of muscle activity to functional development of the hindlimb, which proceeds rapidly around P15. Both the EMG characteristics and the activation pattern showed marked changes with age. Initially, the EMG bursts were irregular and protracted. The activity level in the two muscles, in particular in GM, seemed to be low. Until P14, the motor units of GM showed a tendency towards synchronization. The EMG of TA consisted of an adult-like interference pattern from the youngest age studied. Although co-contraction of TA and GM was sometimes observed until P14, reciprocal activation of the muscles was evident at all ages. The timing of the alternating pattern became more accurate with age. The activity level in both muscles increased markedly from P15. These changes were reflected in the form factor (coefficient of variability) of the EMG and, to a lesser extent, in the power spectra. The time course of these changes bears a close temporal relationship to the development of locomotion. These results suggest that the degree of muscle activation is a decisive factor with respect to locomotor development. It is proposed that this is related to the maturation of supraspinal control.

Aging↗

Consequences of cerebellar lesions at early and later ages: clinical relevance of animal experiments.

Animal experiments demonstrated that reactions of the brain after early lesions differ from those after lesions at adult age. Detailed knowledge on the neuroanatomical and neurophysiological consequences of brain lesions was obtained in humans and will be gained from lesion experiments in animals. Prerequisites for extrapolating animal data to the clinical situation are discussed: knowledge on the maturational stage at which the lesion occurs and the behavioral expression of the damaged neural system. The extensive remodelling after early unilateral cerebellar hemispherectomy and its consequences for behavioural development in the rat are presented and discussed.

Aging↗

Development of locomotion in the rat: the significance of early movements.

The development of the nervous system is determined by an interaction between genetic and epigenetic factors. We investigated the possible role of proprioceptive afferent input in the development of locomotion in the rat. Kinematic analysis of locomotion in normal rats reveals a marked transition from immature overground locomotion into the adult pattern around the 15th postnatal day. Around this age, the timing of EMG activity in the tibialis anterior and the gastrocnemius muscle in the hindpaw gains accuracy and the intensity of the EMG increases. In the soleus muscle we observed an increased regularity in the shape of individual motor unit potentials. Neuroanatomical research revealed the occurrence of dendrite bundles in the motoneuronal pool of the soleus muscle pool from the 16th day as the result of a reorganisation. Immobilisation of one hindlimb in an extended position by casts around the leg from the first till the 20th postnatal day does not interfere with the development of dendrite bundles in the soleus motoneuronal pool. However, we demonstrated long lasting abnormalities in the timing of the EMG activation patterns in the gastrocnemius and the tibialis anterior muscles. It is conceivable that the experimental interference with afferent feed back is the causative factor of these functional abnormalities.

Aging↗

Development of posture in the rat.

Postural development has not attracted much attention in investigations of neuro-ontogeny. In the rat, motor behaviours have been studied repeatedly but the development of postural control has been largely neglected. In the present study we have taken inventory of behavioural aspects of postural development. Postures and postural skills of 10 pups were 3-dimensionally recorded on video tape from the 2nd to the 20th day. The development of posture may be subdivided into three periods. During the first period, lasting until the 4th or 5th day, neonates were unable to lift their trunk from the floor, and the only indication for postural activity being head lifting. From then until the 12th-13th day, pups were able to walk, though staggering, and in addition they groomed and reared with forelimb support. From then, in a rapid development lasting until day 16, the adult type of fluent locomotion developed as well as grooming and rearing without support. In addition, complex motor acts developed. These results are discussed in the perspective of the structural and functional development of postural systems.

Animals↗

Descending pathways and the hopping response in the rabbit.

Descending pathways were studied in 5 adult rabbits by means of HRP, injected in the cervical spinal cord (in C2 and C3) at the right side. Results indicate the existence of pathways from the contralateral motor cortex, bilateral projections from the red nuclei, from the vestibular nuclei and from several nuclei in the reticular formation.

Animals↗

Structural changes of the soleus and the tibialis anterior motoneuron pool during development in the rat.

The morphological development of motoneuron pools of two hindlimb muscles of the rat, soleus (SOL) and tibialis anterior (TA), was studied in rats ranging in age between 8 and 30 postnatal days (P8-P30). Motoneurons were retrogradely labelled by injecting a cholera toxin B subunit solution directly into the muscles. This resulted in extensive labelling of motoneurons as well as their dendritic trees. The distribution of cross sectional areas of neuronal somata was determined for both muscles at various ages. Somal size increased considerably between P8 and P12, whereas growth was moderate between P12 and P20. The size distribution of SOL motoneurons was bimodal from P20, whereas the size distribution of TA motoneurons remained largely unimodal. The morphological development of the dendritic tree was studied qualitatively. The development of dendritic arborization within the SOL and the TA motoneuron pool showed major differences. The arborization pattern of dendrites of TA motoneurons was basically multipolar at all ages. In contrast, dendrites of SOL neurons tended to line up with the rostro-caudal axis and became organized in longitudinal bundles from P16 onwards. The relatively late appearance of dendrite bundles in the soleus motoneuron pool suggests that they might be related to the fine-tuning of neuronal activity rather than patterning of motor activity. The occurrence of dendrite bundles in SOL and not in TA motoneuron pools suggests that they may be related to the different afferent organization of this postural muscle or to its tonic activation pattern.

Afferent Pathways↗

Locomotor development in undernourished rats.

The effects of undernutrition on the development of locomotion were studied in fourteen rats. Mothers received about 40% of normal quantities of standard laboratory food from the 5th day of gestation until weaning at the 21st day after birth. Qualitative as well as quantitative aspects of locomotion were studied from the 12th to the 30th day and compared to data from ten control rats. Undernutrition leads to delayed and prolonged developmental changes in locomotion. The adult type of locomotion, which in normal rats develops from the 14th day occurs after the 15th or 16th day in undernourished rats and this development also lasts longer. Locomotion remains mildly abnormal, at least until the 30th day. Especially at lower speeds, walking is clumsy because of an unusual brisk onset, a slightly unsteady gait and non-fluent paw movements. These results are discussed in the perspective of data on brain and muscle development in rats after early undernutrition.

Aging↗

Increased cell number in remaining cerebellar nuclei after cerebellar hemispherectomy in neonatal rats.

After cerebellar hemispherectomy before the 10th day of life aberrant cerebello-rubral projections develop from the nuclei in the remaining hemisphere, which terminate on the ipsilateral side. These aberrant fibres stem from separate parent cells in the lateral and interposed nuclei. The problem addressed by the present study was whether the number of neurones in these nuclei is increased after early cerebellar hemispherectomy. Results demonstrate that the number of neurones was increased by 50-60%. The volumes of the nuclei were also increased (14-31%) but much less so, which indicates a relative decrease in neuropil per neuron.

Animals↗

At what age is the developing cerebral cortex of the rat comparable to that of the full-term newborn human baby?

By means of a comparative study of experimental data from the literature we estimated at what age the rat cerebral cortex corresponds to that of the full-term newborn human infant with regard to the degree of maturation. As a result of this study we suggest that the 12-13-day-old rat pup fulfills this criterion. This finding should be of use to scientists who use the rat for studying certain processes assumed to occur in the human cerebral cortex around full-term birth.

Animals↗

The development of locomotion in the rat.

The development of free walking was studied in rats between postnatal days 10 and 20. Spontaneous quadruped walking with the ventral surface of the body off the floor was first observed at postnatal day 11. Locomotion remained clumsy and invariably slow during the next few days, but a rapid transformation into the mature pattern of locomotion occurred around postnatal day 15. This transformation involved changes in quantitative parameters of locomotion as well as a change in the movement pattern of the hindlimb. A swimming-like movement characterized by abduction, rotation and hyperextension of the paw was replaced by the digitigrade adult pattern without marked rotation. Joint angle trajectories of the major joints during the step cycle changed considerably during the transitional period. The results, which are to serve as a framework for ongoing research into the effects of early undernutrition and movement restriction upon motor function, are discussed in the perspective of developmental changes in the nervous and musculoskeletal system.

Aging↗

The effects of brain lesions on the "hopping reaction" in newborn and adult rabbits: a model for studying age dependent recovery.

In 5 groups of rabbits (0-1, 2-3, 4-5, 6-7 and 12-13 weeks old) the left frontal, parieto-temporal and occipital cortex were removed. Beginning two weeks after the operations the hopping reaction was tested during 15 weeks. It was found in the groups operated 0-1, 2-3 and 4-5 weeks after birth, that the hopping reaction developed normally. This was not the case in the animals operated 6-7 and 12-13 weeks after birth. Brightness descrimination with the left and right eye was tested in the same animals, beginning 12 weeks after the operation. Contrary to the motor system, no age-development recovery was found in the visual system. In all age groups, brightness discrimination with the eye contralateral to the lesion was impaired.

Aging↗

The hopping response after two-stage cortical ablation in young and adult rabbits.

In a group of 14 rabbits aged between 14 and 21 days a hemidecortication was performed in the left hemisphere. A normal monopedal lateral hopping response developed in both forelegs. At adult age, 13 weeks after the first lesion, the remaining cortex on the right side was ablated. Three days afterwards the hopping response was tested again. In all animals, the hopping response remained positive in the right foreleg, contralateral to the lesioning at early age. However, in 10 out of 14 animals the response was absent on the left side, contralateral to the recent lesion. These results show that the hopping response is not mediated by corticofugal connections of the remaining hemisphere of the foreleg contralateral to the early lesion.

Age Factors↗

Do early lesions affect cell death in the central nervous system? A study on the effects of early cerebellar hemispherectomy in rats.

Cell death patterns in the lateral and interposed nuclei were compared in control rats and rats in whom a unilateral cerebellar hemispherectomy was performed at day 2 of life. Both groups were studied between days 2 and 20 of life. Pyknotic cells and live neuronal and glial cells were counted from Nissl stained sections. After correction of these values, pyknotic to live cell ratios were calculated. In the lateral nucleus of normal rats, around 14-28 pyknotic cells per 1,000 live cells occurred from day 2 to day 12. Thereafter this value decreased, and from day 16 less than 3 pyknotic/1,000 live cells were observed. In the interposed nuclei, 18-28 pyknotic cells/1,000 live cells occurred at day 2, and from this age onward values gradually decreased. At day 20 values ranged around 1.6/1,000. After unilateral cerebellar hemispherectomy, values in both nuclei began to decrease as early as from day 8. Results from the present study strongly suggest that these cells are prevented from dying because they find an aberrant synaptic target in the ipsilateral red nucleus. Our results demonstrate that early lesions interfere with the regulation of fundamental processes of neuro-ontogeny.

Animals↗

Determining nucleolar multiplicity and cell number from sectional data.

The occurrence of more than one nucleolus within the cellular nucleus (polynucleolarity) is a well-known phenomenon during the proliferative cell cycle, both under normal and pathological conditions (e.g. neoplasia). It can also be observed in neuronal nuclei at early stages of their maturation. Polynucleolarity merits investigation for cytological reasons. In an histological section, the observed number of nucleoli in a nucleus may be smaller than the actual number. In order to estimate the true distribution of the number of nucleoli per nucleus from the observed distribution, the mathematical relation between these distributions is derived on the basis of rather restrictive stereological assumptions. It is indicated how these distributions can be estimated from the data available and how the statistical uncertainties involved can be expressed. This paper arose from making cell counts. Two methods may be applied: all visible nuclear profiles are counted, nuclear profiles are only included if at least one nucleolus is visible in the section. We recommended a combination of these two methods. An advantage of our theory for determining cell number is that one can often manage without the rather restrictive stereological assumptions needed hitherto. The advantage of expressing statistical uncertainties in estimated nucleolar multiplicity probabilities and cell numbers is indicated.

Animals↗

Electrical activity in the red nuclei of rats and the effects of hemicerebellectomy at young ages.

Extracellular activity in the red nuclei in different behavioural states was investigated in control adult rats and in adults rats who had previously undergone a cerebellar hemispherectomy on their 2nd, 5th, 10th or 20th day. In addition to visual analysis, spectra and coherence functions were computed from the signals during quiescence and movements. Preceding and during movements a particular pattern, characterized by a regular rhythm between 7.5 and 8.0 Hz occurs. Inter-rubral coherences are high at the specific pattern frequency. In rats with a cerebellar hemispherectomy - irrespective of the age at lesioning - power spectra from both red nuclei differ markedly from each other during quiescence. When movements occur, rats operated at the 20th day show a pattern in both red nuclei similar to that found in control rats. However, in rats lesioned at the 5th or 10th day the specific pattern frequency is much lower while in rats operated at the 2nd day no specific patterning of red nuclei activity is evident.

Afferent Pathways↗

CNS plasticity after hemicerebellectomy in the young rat. Quantitative relations between aberrant and normal cerebello-rubral projections.

The double labelling technique has been applied to study the quantitative relations between aberrant and normal cerebello-rubral projections in rats hemicerebellectomized on the 2nd, 5th, 10th, 20th or 30th day after birth, respectively. In the group of rats lesioned on the 2nd day about 30% of cells in the lateral nucleus and 20% in the interpositus nuclei are labelled retrogradely by the fluorescent tracer injected in the aberrant ipsilateral projection area. These values decreased in the groups of rats operated on the 5th or 10th day and reached values of about 1-2% in rats lesioned on the 20th or 30th day. These values have been also found in control rats. Both in experimental rats and in control rats less than 0.5% of cells are double labelled from both projection areas. This implies that the aberrant cerebello-rubral fibres stem from separate parent cells and are not collaterals from normally projecting fibres.

Animals↗

The effects of cerebellar hemispherectomy in the young rat. I. Behavioral sequelae.

The effects of unilateral cerebellar hemispherectomy in rats operated on the 5th, 10th and 30th days were investigated. Their locomotor behaviour was studied longitudinally until the age of 360 days. Locomotion remained impaired to a variable extent in all experimental groups. Rats operated on the 30th day showed fewer deviations in locomotion than rats operated on the 5th or 10th day.

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