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Biomedical subjects

A Gramsbergen

Publications and source records attributed to A Gramsbergen.

At least 19 recordsLinked to original sources
PubMed2005

Development of postural muscles and their innervation.

Control of posture is a prerequisite for efficient motor performance. Posture depends on muscles capable of enduring contractions, whereas movements often require quick, forceful muscle actions. To serve these different goals, muscles contain fibers that meet these different tasks. Muscles with strong postural functions mainly consist of slow muscle fibers with a great resistance against fatigue. Flexor muscles in the leg and arm muscles are mainly composed of fast muscle fibers producing relatively large forces that are rapidly fatigable. Development of the neuromuscular system continues after birth. We discuss in the human baby and in animal experiments changes in muscle fiber properties, regression from polyneural into mononeural innervation, and developmental changes in the motoneurons of postural muscles during that period. The regression of poly-neural innervation in postural muscles and the development of dendrite bundles of their motoneurons seem to be linked to the transition from the immature into the adult-like patterns of moving and postural control.

Animals↗
PubMed2005

Cerebellar development and plasticity: perspectives for motor coordination strategies, for motor skills, and for therapy.

The role of the mammalian cerebellum ranges from motor coordination, sensory-motor integration, motor learning, and timing to nonmotor functions such as cognition. In terms of motor function, the development of the cerebellum is of particular interest because animal studies show that the development of the cerebellar cortical circuitry closely parallels motor coordination. Ultrastructural analysis of the morphological development of the cerebellar circuitry, coupled with the temporal and spatial identification of the neurochemical substrates expressed during development, will help to elucidate their roles in the establishment of the cerebellar circuitry and hence motor activity. Furthermore, the convenience of a number of naturally occurring mouse mutations has allowed a functional dissection of the various cellular elements that make up the cerebellar circuitry. This understanding will also help in the approach to possible therapies of pathologies arising during development because the cerebellum is especially prone to such perturbation because of its late development.

Animals↗
PubMed2004

Behavioural consequences of hypergravity in developing rats.

Gravity represents a stable reference for the nervous system. When the individual is increasing in size and weight, gravity may influence several aspects of the sensory and motor developments. To clarify this role, we studied age-dependent modifications of several exteroceptive and proprioceptive reflexes in five groups of rats conceived, born and reared in hypergravity (2 g). Rats were transferred to normal gravity (1 g) at P5 (post-natal day 5), P10, P15, P21, and P27. Aspects of neural development and adaptation to 1 g were assessed until P40. Hypergravity induced a delay in growth and a retardation in the development of contact-righting, air-righting, and negative geotaxis. However, we found an advance in eye opening by about 2-3 days in HG-P5 and HG-P10 rats and an increase in grip-time. No differences were found in tail and grasp reflexes. Our results show that hypergravity leads to a retarded development of motor aspects which are mainly dependent upon the vestibular system.

Age Factors↗
PubMed2004

Transection of peripheral nerves, bridging strategies and effect evaluation.

Disruption of peripheral nerves due to trauma is a frequently occurring clinical problem. Gaps in the nerve are bridged by guiding the regenerating nerves along autologous grafts or artificial guides. This review gives an overview on the different methods of nerve repair techniques. Conventional suturing techniques are discussed as well as the use of e.g. biological, synthetic, non-degradable or degradable nerve guides. Functional assessment showed that repair of a gap with a bio-degradable guide is superior to that with autologous grafts. But still, long lasting changes were observed in the Sciatic Function Index (SFI), abnormal walking patterns, disturbed Electro Myo Graphic (EMG) patterns, next to shifts in the histochemical properties of the muscles and longlasting abnormalities in neuromuscular contacts. These phenomena are explained by an at-random reinnervation. When transecting the nerve at young ages, this did not lead to enhanced recovery. Rearing rats operated at adult age in an enriched environment, also had no beneficial effect. Future research should aim at developing longer guides, possibly lined with Schwann cells, or additives, improving specific reinnervation of the former target areas.

Absorbable Implants↗
PubMed2004

Corticotropin-releasing factor and urocortin differentially modulate rat Purkinje cell dendritic outgrowth and differentiation in vitro.

The precise outgrowth and arborization of dendrites is crucial for their function as integrators of signals relayed from axons and, hence, the functioning of the brain. Proper dendritic differentiation is particularly resonant for Purkinje cells as the intrinsic activity of this cell-type is governed by functionally distinct regions of its dendritic tree. Activity-dependent mechanisms, driven by electrical signaling and trophic factors, account for the most active period of dendritogenesis. An as yet unexplored trophic modulator of Purkinje cell dendritic development is corticotropin-releasing factor (CRF) and family member, urocortin, both of which are localized in climbing fibers. Here, we use rat organotypic cerebellar slice cultures to investigate the roles of CRF and urocortin on Purkinje cell dendritic development. Intermittent exposure (12 h per day for 10 days in vitro) of CRF and urocortin induced significantly more dendritic outgrowth (45% and 70%, respectively) and elongation (25% and 15%, respectively) compared with untreated cells. Conversely, constant exposure to CRF and urocortin significantly inhibited dendritic outgrowth. The trophic effects of CRF and urocortin are mediated by the protein kinase A and mitogen-activating protein kinase pathways. The study shows unequivocally that CRF and urocortin are potent regulators of dendritic development. However, their stimulatory or inhibitory effects are dependent upon the degree of expression of these peptides. Furthermore, the effects of CRF and urocortin on neuronal differentiation and re-modeling may provide a cellular basis for pathologies such as major depression, which show perturbations in the expression of these stress peptides.

Analysis of Variance↗
PubMed2003

Corticotropin-releasing factor receptor types 1 and 2 are differentially expressed in pre- and post-synaptic elements in the post-natal developing rat cerebellum.

Corticotropin-releasing factor (CRF)-like proteins act via two G-protein-coupled receptors (CRF-R1 and CRF-R2) playing important neuromodulatory roles in stress responses and synaptic plasticity. The cerebellar expression of corticotropin-releasing factor-like ligands has been well documented, but their receptor localization has not. This is the first combination of a light microscopic and ultrastructural study to localize corticotropin-releasing factor receptors immunohistologically in the developing rat cerebellum. Both CRF-R1 and CRF-R2 were expressed in climbing fibres from early stages (post-natal day 3) to the adult, but CRF-R2 immunoreactivity was only prominent throughout the molecular layer in the posterior cerebellar lobules. CRF-R1 immunoreactivity was concentrated in apical regions of Purkinje cell somata and later in primary dendrites exhibiting a diffuse cytoplasmic appearance. In Purkinje cells, CRF-R1 immunoreactivity was never membrane bound post-synaptically in dendritic spines while CRF-R2 immunoreactivity was found on plasmic membranes of Purkinje cells from post-natal day 15 onwards. We conclude that the localization of these receptors in cerebellar afferents implies their pre-synaptic control of the release of corticotropin-releasing factor-like ligands, impacting on the sensory information being transmitted from afferents. Furthermore, the fact that CRF-R2 is membrane bound at synapses, while CRF-R1 is not, suggests that ligands couple to CRF-R2 via synaptic transmission and to CRF-R1 via volume transmission. Finally, the distinct expression profiles of receptors along structural domains of Purkinje cells suggest that the role for these receptors is to modulate afferent inputs.

Animals↗
PubMed2003

Functional nerve recovery after bridging a 15 mm gap in rat sciatic nerve with a biodegradable nerve guide.

Recovery of nerve function was evaluated after bridging a 15 mm sciatic nerve gap in 51 rats with a biodegradable poly(DL-lactide-epsilon-caprolactone) nerve guide. Recovery of function was investigated by analysing the footprints, by analysing video recordings of gait, by electrically eliciting the withdrawal reflex, by nerve conduction velocity and by electromyography (EMG). Sensory nerve function recovered as measured by electrostimulation. Motor nerve function partly recovered but electromyograms remained abnormal throughout the study. We conclude that functional reinnervation by regenerating axons occurs after bridging a 15 mm nerve gap with a biodegradable poly(DL-lactide-epsilon-caprolactone) nerve guide, but the walking patterns remain abnormal. Video analysis is a useful tool to record and analyse the walking patterns of rats. Further studies are necessary to investigate the possibility of obtaining selective reinnervation of specific muscles.

Animals↗
PubMed2002

The localisation of urocortin in the adult rat cerebellum: a light and electron microscopic study.

Light and electron microscopic immunocytochemistry was used to identify the cellular and subcellular localisation of urocortin in the adult rat cerebellum. Urocortin immunoreactivity (UCN-ir) was visualised throughout the cerebellum, yet predominated in the posterior vermal lobules, especially lobules IX and X, the flocculus, paraflocculus and deep cerebellar nuclei. Cortical immunoreactivity was most evident in the Purkinje cell layer and molecular layer. Reaction product, though sparse, was found in the somata of Purkinje cells, primarily in the region of the Golgi apparatus. Purkinje cell dendritic UCN-ir was compartmentalised, with it being prevalent in proximal regions especially where climbing fibres synapsed, yet absent in distal regions where parallel fibres synapsed. In the Purkinje cell layer, the labelling was also contained in axonal terminals, synapsing directly on Purkinje cell somata. These were identified as axon terminals of basket cells based on their morphology. Terminals of stellate cells in the upper molecular layer also expressed the peptide. Whilst somata of inferior olivary neurones showed intense immunoreactivity, axonal labelling was indistinct, with only the terminals of climbing fibres containing reaction product. UCN-ir in the mossy fibre-parallel fibre system was restricted to mossy fibre rosettes of mainly posterior lobules and the varicose terminals of parallel fibres. Furthermore, labelling also was prevalent in glial perikarya and their sheaths. The current study shows, firstly, that urocortin enjoys a close ligand-receptor symmetry in the cerebellum, probably to a greater degree than corticotropin-releasing factor since corticotropin-releasing factor itself is found exclusively in the two major cerebellar afferent systems. Its congregation in excitatory and inhibitory axonal terminals suggests a significant degree of participation in the synaptic milieu, perhaps in the capacity as a neurotransmitter or effecting the release of co-localised neurotransmitters. Finally, its unique distribution in the Purkinje cell dendrite might serve as an anatomical marker of discrete populations of dendritic spines.

Age Factors↗
PubMed2001

Biodegradable p(DLLA-epsilon-CL) nerve guides versus autologous nerve grafts: electromyographic and video analysis.

The aim of this study was to evaluate the functional effects of bridging a gap in the sciatic nerve of the rat with either a biodegradable copolymer of DL-lactide and epsilon-caprolactone [p(DLLA-epsilon-CL)] nerve guide or an autologous nerve graft. Electromyograms (EMGs) of the gastrocnemius (GC) and tibialis anterior (TA) muscles were recorded 3.5 and 5 months after bridging the nerve gaps. Furthermore, the rats' gait was recorded on video and the quality of the gait was analyzed. EMG patterns of the contralateral nonoperated side were essentially normal. The EMG patterns on the operated side were irregular in all animals, but the quality of gait was better in the nerve guide group. We conclude that the surgical technique (nerve guide or nerve graft) does not influence the occurrence of abnormal EMG patterns, but gait improves to a greater extent when the nerve gap is bridged by a nerve guide.

Animals↗
PubMed2001

Muscle differentiation after sciatic nerve transection and reinnervation in adult rats.

Reinnervation after peripheral nerve transections generally leads to poor functional recovery. In order to study whether changes in muscles might be a contributing factor in this phenomenon we studied muscle morphology and fibre type distributions after sciatic nerve transection in the rat hind limb. Proximally, before the bifurcation in the tibial and common peroneal nerve, a 12 mm segment of the sciatic nerve was resected, reversed and re-implanted as an autologous nerve graft. After survival periods of 7, 15 and 21 weeks the lateral gastrocnemius, tibialis anterior and soleus muscles were dissected, stained with mATP-ase, and fibre type distributions were studied. In addition, numbers of muscle fibres were counted, and cross sectional areas were calculated. After 7 weeks, cross sectional areas were decreased in all muscles. In the gastrocnemius and tibialis anterior muscles the fibre number remained unaltered but the hypotrophy had been reversed at later ages. The number of muscle fibres in the soleus muscle remained decreased over the entire period of observation. The percentages of type II fibres in the gastrocnemius and tibialis anterior muscles were decreased at 7 and 15 weeks but these again approached normal values at 21 weeks. The type I fibres, however, remained arranged in groups. In the soleus muscle a large increase in the percentage of type II muscle fibres was observed and this remained until 21 weeks. We conclude that a non-selective reinnervation and later readjustments by regression of polyneural innervation may in part explain the changes in distributions of various fibre types.

Animals↗
PubMed2001

A new technique for simultaneously recording EMG and movements in experimental animals.

In this protocol a new system is presented for recording EMG signals from leg and trunk muscles along with video-recording of leg and trunk movements. The system comprises a front-end amplifier consisting of a reference amplifier, a differential amplifier with a filter combination and an analog to digital converter (ADC). A fiber optic transmitter connects the front end amplifier via a fiber cable to a receiver board placed in a personal computer (PC). A dedicated software programme (POLY) was written to process the physiological signals on the PC. The physiological recordings can be synchronized to video-recordings and the principles of this technique are given. The system allows to record artifact-free physiological signals and also to link activation patterns in muscles with kinematic aspects of movements.

Animals↗
PubMed2001

Sciatic nerve transection in adult and young rats: abnormal EMG patterns during locomotion.

Transections of peripheral nerves usually lead to serious handicaps. In order to enhance insights into the poor functional recovery, we studied the effects of a unilateral sciatic nerve lesion in adult and young rats. Electromyographic (EMG) patterns of the tibialis anterior (a hindlimb flexor) and the gastrocnemius muscle (a hindlimb extensor) during walking were recorded after transecting the sciatic nerve at adult age and at the 10th postnatal day. After recovery periods lasting up to 21 weeks, EMG patterns in the hindleg muscles during locomotion were highly abnormal, irrespective of the age at lesioning. Electromyographic bursts were markedly irregular and, generally, coactivation of these antagonists was observed during walking. Other evidence has shown that after peripheral nerve transection, nerves randomly reinnervate their target muscles and we conclude that the patterns of muscle activity may be associated with the properties of foreign, as well as genuine, motor nerves. Behaviourally, walking patterns after a transection at adult age are markedly abnormal but, after transection at the 10th day, locomotion is much less disturbed. The finding of a discrepancy between a near normal walking pattern in rats operated on at a young age and severely disturbed EMG activity may be due to subtle readjustments in the force recruitment in the respective muscles, despite a random reinnervation by the sciatic nerve branches. These compensatory readjustments are particularly prominent after transection at an early age.

Age Factors↗
PubMed2001

Transection of the sciatic nerve and reinnervation in adult rats: muscle and endplate morphology.

The functional recovery after peripheral nerve lesions is generally poor. We studied whether changes in muscles after reinnervation might explain such disappointing results. The functional recovery after peripheral nerve lesions is generally poor. Changes in muscle morphology and neuromuscular innervation might partly explain this lack of compensation. In order to test this hypothesis, we studied muscular differentiation in the soleus, gastrocnemius and tibialis anterior muscles at 7, 15 and 21 weeks after a sciatic nerve lesion in adult rats. In the gastrocnemius and tibialis muscles the percentages of type II muscles fibres were decreased at 7 and 15 weeks but at 21 weeks they again approached normal values. The soleus muscle, however, was permanently decreased in size and this muscle, in contrast to the normal soleus muscle, contained mainly type II fibres. The morphology of the endplates showed distinct stages of degeneration and reinnervation. Two weeks after denervation, in rats in which reinnervation was prevented, all 3 muscles contained considerable numbers of morphologically abnormal endplates and, after 7 weeks, no endplates were detected. During reinnervation, endplates showing signs of acetylcholinesterase activity were observed in all 3 muscles from 7 weeks. At later ages a shift towards morphologically normal endplates occurred, but complete recovery was not observed. Endplates in all 3 muscles were polyneurally innervated at 7 weeks. Although these percentages decreased over age, polyneural innervation was still present at 21 weeks. We conclude that the changes in the distribution of fibre types, abnormal endplate morphology and polyneural innervation may in part explain the poor functional recovery after peripheral nerve lesions.

Animals↗
PubMed2001

Normal and abnormal development of motor behavior: lessons from experiments in rats.

In this essay a few relevant aspects of the neural and behavioral development of the brain in the human and in the rat are reviewed and related to the consequences of lesions in the central and peripheral nervous system at early and later age. Movements initially are generated by local circuits in the spinal cord and without the involvement of descending projections. After birth, both in humans and in rats it seems that the development of postural control is the limiting factor for several motor behaviors to mature. Strong indications exist that the cerebellum is significantly involved in this control. Lesions in the CNS at early stages interfere with fundamental processes of neural development, such as the establishment of fiber connections and cell death patterns. Consequently, the functional effects are strongly dependent on the stage of development. The young and undisturbed CNS, on the other hand, has a much greater capacity than the adult nervous system for compensating abnormal reinnervation in the peripheral nervous system. Animal experiments indicated that the cerebellar cortex might play an important part in this compensation. This possibility should be investigated further as it might offer important perspectives for treatment in the human.

Animals↗
PubMed2000

Methods to evaluate functional nerve recovery in adult rats: walking track analysis, video analysis and the withdrawal reflex.

The aim of this study was to compare different methods for the evaluation of functional nerve recovery. Three groups of adult male Wistar rats were studied. In group A, a 12-mm gap between nerve ends was bridged by an autologous nerve graft; in rats of group B we performed a crush lesion of the sciatic nerve and group C consisted of non-operated control rats. The withdrawal reflex, elicited by an electric stimulus, was used to evaluate the recovery of sensory nerve function. To investigate motor nerve recovery we analyzed the walking pattern. Three different methods were used to obtain data for footprint analysis: photographic paper with thickened film developer on the paws, normal white paper with finger paint, and video recordings. The footprints were used to calculate the sciatic function index (SFI). From the video recordings, we also analyzed stepcycles. The withdrawal reflex is a convenient and reproducible test for the evaluation of global sensory nerve recovery. Recording walking movements on video and the analysis of footplacing is a perfect although time-consuming method for the evaluation of functional aspects of motor nerve recovery.

Animals↗