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Biomedical subjects

W Nacimiento

Publications and source records attributed to W Nacimiento.

At least 19 recordsLinked to original sources
PubMed2003

Involuntary stretching during yawning in patients with pyramidal tract lesions: further evidence for the existence of an independent emotional motor system.

A variety of associated movements have been described in patients with pyramidal tract lesions. We report three patients in whom involuntary stretching of an otherwise plegic arm could be observed during yawning. These patients had radiologically verified lesions at different levels of the pyramidal tract. As yawning and stretching are an automatic behavioural pattern in animals, it is likely that stretches during yawning in man are also an automatic motor pattern, usually inhibited in the presence of an intact corticospinal tract. The physiological function of yawning is unclear at present. Yawning might be the somatomotor manifestation of a particular emotional state characterized by boredom and fatigue. Our observation that movements of an otherwise plegic arm occur in patients with pyramidal tract lesions supports therefore the concept of an emotional motor system which has an independent input to motoneurones in the brain stem and the spinal cord.

Adult↗
PubMed2002

Increased expression of the putative axon growth-repulsive extracellular matrix molecule, keratan sulphate proteoglycan, following traumatic injury of the adult rat spinal cord.

Keratan sulphate proteoglycan (KSPG) is a developmentally regulated barrier molecule, directing axonal growth during central nervous system (CNS) formation. The possible re-expression and functional significance of KSPG in preventing axon regeneration following spinal cord injury (SCI) is poorly understood. In the present investigation, the spatio-temporal expression of KSPG was studied following experimental SCI. There was no indication of sparing of axons at the lesion epicentre following severe compression injury. By 7 days post operation (p.o.) a diffuse increase of KSPG immunoreactivity (KSPG-IR) was observed in the parenchyma surrounding the lesion. This was followed by a delayed (21-28 days p.o.) and largely heterogeneous increase of KSPG-IR in the lesion epicentre, which revealed both cellular and extracellular matrix-like distribution patterns. Although no re-growth of anterogradely labelled corticospinal axons was observed, many 200-kDa neurofilament (NF)-positive axons could be detected growing into the connective tissue scar. This phase of spontaneous axonal re-growth was closely associated with a framework of glial cells (including Schwann cells from damaged local spinal nerve roots) that had migrated into the lesion site. The spontaneous nerve fibre re-growth could be detected in both KSPG-rich and KSPG-poor territories. The present data suggest that the lesion-induced up-regulation of KSPG-IR may have contributed to the lack of corticospinal axon re-growth. However, the lack of any direct spatio-temporal correlation between the distribution of raised KSPG-IR and spontaneous NF-positive axonal regeneration suggests that at least some populations of axons can resist the putative inhibitory effects of this extracellular matrix molecule.

Animals↗
PubMed2001

Computer-assisted quantification of axo-somatic boutons at the cell membrane of motoneurons.

This paper presents a system for computer-assisted quantification of axo-somatic boutons at motoneuron cell-surface membranes. Different immunohistochemical stains can be used to prepare tissue of the spinal cord. Based on micrographs displaying single neurons, a finite element balloon model has been applied to determine the exact location of the cell membrane. A synaptic profile is extracted next to the cell membrane and normalized with reference to the intracellular brightness. Furthermore, a manually selected reference cell is used to normalize settings of the microscope as well as variations in histochemical processing for each stain. Thereafter, staining, homogeneity, and allocation of boutons are determined automatically from the synaptic profiles. The system is evaluated by applying the coefficient of variation (Cv) to repeated measurements of a quantity. Based on 1856 motoneuronal images acquired from four animals with three stains, 93% of the images are analyzed correctly. The others were rejected, based on process protocols. Using only rabbit anti-synaptophysin as primary antibody, the correctness increases above 96%. Cv values are below 3%, 5%, and 6% for all measures with respect to stochastic optimization, cell positioning, and a large range of microscope settings, respectively. A sample size of about 100 is required to validate a significant reduction of staining in motoneurons below a hemi-section (Wilcoxon rank-sum test, alpha = 0.05, beta = 0.9). Our system yields statistically robust results from light micrographs. In future, it is hoped that this system will substitute for the expensive and time-consuming analysis of spinal cord injury at the ultra-structural level, such as by manual interpretation of nonoverlapping electron micrographs.

Animals↗
PubMed2000

Presumed capillary telangiectasia of the pons: MRI and follow-up.

Capillary telangiectasia is a vascular abnormality primarily of the brainstem. The clinical relevance is unclear as is the association with clearly pathologic findings such as cavernous haemangioma. We report on four cases with capillary telangiectasia proven by follow-up and describe the imaging characteristics. T2 abnormality was only observed in half of the patients as was the presence of a discernable collecting vein. Whereas two cases were incidental findings in neurologically normal persons and one had symptoms clearly attributable to lacunar stroke, one patient may have had symptoms due to the vascular abnormality in the pons.

Adult↗
PubMed2000

Major histocompatibility complex class II expression by activated microglia caudal to lesions of descending tracts in the human spinal cord is not associated with a T cell response.

Lesion-induced microglial/macrophage responses were investigated in post-mortem human spinal cord tissue of 20 patients who had died at a range of survival times after spinal trauma or brain infarction. Caudal to the spinal cord injury or brain infarction, a strong increase in the number of activated microglial cells was observed within the denervated intermediate grey matter and ventral horn of patients who died shortly after the insult (4-14 days). These cells were positive for the leucocyte common antigen (LCA) and for the major histocompatibility complex class II antigen (MHC II), with only a small proportion staining for the CD68 antigen. After longer survival times (1-4 months), MHC II-immunoreactivity (MHC II-IR) was clearly reduced in the grey matter but abundant in the white matter, specifically within the degenerating corticospinal tract, co-localising with CD68. In this fibre tract, elevated MHC II-IR and CD68-IR were still detectable 1 year after trauma or stroke. It is likely that the subsequent expression of CD68 on MHC II-positive microglia reflects the conversion to a macrophage phenotype, when cells are phagocytosing degenerating presynaptic terminals in grey matter target regions at early survival times and removing axonal and myelin debris in descending tracts at later survival times. No T or B cell invasion or involvement of co-stimulatory B7 molecules (CD80 and CD86) was observed. It is possible that the up-regulation of MHC II on microglia that lack the expression of B7 molecules may be responsible for the prevention of a T cell response, thus protecting the spinal cord from secondary tissue damage.

Aged↗
PubMed2000

Peripheral but not central axotomy induces changes in Janus kinases (JAK) and signal transducers and activators of transcription (STAT).

Nerve injury leads to the release of a number of cytokines which have been shown to play an important role in cellular activation after peripheral nerve injury. The members of the signal transducer and activator of transcription (STAT) gene family are the main mediators in the signal transduction pathway of cytokines. After phosphorylation, STAT proteins are transported into the nucleus and exhibit transcriptional activity. Following axotomy in rat regenerating facial and hypoglossal neurons, a transient increase of mRNA for JAK2, JAK3, STAT1, STAT3 and STAT5 was detected using in situ hybridization and semi-quantitative polymerase chain reaction (PCR). Of the investigated STAT molecules, only STAT3 protein was significantly increased. In addition, activation of STAT3 by phosphorylation on position Tyr705 and enhanced nuclear translocation was found within 3 h in neurons and after 1 day in astrocytes. Unexpectedly, STAT3 tyrosine phosphorylation was obvious for more than 3 months. In contrast, none of these changes was found in response to axotomy of non-regenerating Clarke's nucleus neurons, although all the investigated models express c-Jun and growth-associated protein-43 (GAP-43) in response to axonal injury. Increased expression of Janus kinase (JAK) and STAT molecules after peripheral nerve transection suggests changes in the responsiveness of the neurons to signalling molecules. STAT3 as a transcription factor, which is expressed early and is activated persistently until the time of reinnervation, might be involved in the switch from the physiological gene expression to an 'alternative program' activated only after peripheral nerve injury.

Animals↗
PubMed2000

Attempted endogenous tissue repair following experimental spinal cord injury in the rat: involvement of cell adhesion molecules L1 and NCAM?

It is widely accepted that the devastating consequences of spinal cord injury are due to the failure of lesioned CNS axons to regenerate. The current study of the spontaneous tissue repair processes following dorsal hemisection of the adult rat spinal cord demonstrates a phase of rapid and substantial nerve fibre in-growth into the lesion that was derived largely from both rostral and caudal spinal tissues. The response was characterized by increasing numbers of axons traversing the clearly defined interface between the lesion and the adjacent intact spinal cord, beginning by 5 days post operation (p.o.). Having penetrated the lesion, axons became associated with a framework of NGFr-positive non-neuronal cells (Schwann cells and leptomeningeal cells). Surprisingly few of these axons were derived from CGRP- or SP-immunoreactive dorsal root ganglion neurons. At the longest survival time (56 days p.o.), there was a marked shift in the overall orientation of fibres from a largely rostro-caudal to a dorso-ventral axis. Attempts to identify which recognition molecules may be important for these re-organizational processes during attempted tissue repair demonstrated the widespread and intense expression of the cell adhesion molecules (CAM) L1 and N-CAM. Double immunofluorescence suggested that both Schwann cells and leptomeningeal cells contributed to the pattern of CAM expression associated with the cellular framework within the lesion.

Animals↗
PubMed1999

Differential distribution of immunoreactivity in the developing rat spinal cord revealed by the monoclonal antibody Py.

Monoclonal antibody Py was developed as a useful tool for the identification of large diameter neurons of the adult rat central nervous system [Woodhams et al., J. Neurosci., 9 (1989) 2170-2181]. Here, we present a detailed light-microscopic study of the distribution of Py-immunoreactivity in the developing rat spinal cord. The first cells which demonstrated Py-immunoreactivity were the motoneurons in layer IX of the gray matter at embryonic day 15. These cells, including their axons and dendrites, remained Py-immunoreactive throughout subsequent developmental stages into adulthood and were the most intensely stained cells in the adult rat spinal cord. Other cell populations which became Py-immunoreactive during development were neurons in layers III-VIII, and large-to-medium diameter neurons of the dorsal root ganglion (DRG). Transient Py-immunoreactivity was observed in the distal portions of DRG axons as well as in the ascending fibers in the dorsal funiculus. Py-immunoreactive fibers could be detected in the ventral most part of the dorsal funiculus (corticospinal tract area), even at embryonic ages prior to the arrival of corticospinal fibers. The localization and transient expression of the antigen recognized by the Py-antibody in developing rat spinal cord strongly suggests an important role of this molecule in stabilization and/or plasticity of the neuronal cytoskeleton. The results presented here form the foundation for the use of Py-immunocytochemistry to study well-defined cell populations under a range of experimental and pathological conditions.

Animals↗
PubMed1999

Astrocytes re-express nestin in deafferented target territories of the adult rat hippocampus.

Up-regulation of the intermediate filament protein, nestin, is a sensitive indicator for the extent of astrocytic activation in regions of CNS close to the point of injury. However, it remains unclear whether activated astrocytes in distant, deafferented CNS territories are also capable of nestin re-expression. Here, we demonstrate that traumatic injury to the dentate gyrus is followed by the rapid but transient expression of nestin in astrocytes located in the stratum lucidum of field CA3. Up-regulation of nestin was first detected at 1 day, was still visible at 14 days, and returned to close to control levels by 28 days post-injury. The present investigation clearly demonstrates the sensitivity of nestin expression as a indicator of astroglial activation in hippocampal target territories undergoing deafferentation-related changes.

Afferent Pathways↗
PubMed1999

GAP-43 (B-50) and C-Jun are up-regulated in axotomized neurons of Clarke's nucleus after spinal cord injury in the adult rat.

The growth-associated protein GAP-43 (B-50) and the transcription factor C-Jun are involved in regeneration of the injured nervous system. In this study, we investigated the possibility of the induction of GAP-43 and C-Jun in axotomized neurons of Clarke's nucleus (CN) in adult rats, of which a large population undergoes degeneration several weeks after a low thoracic lateral funiculotomy of the spinal cord. In situ hybridization and immunohistochemistry revealed a transient up-regulation of GAP-43 mRNA, C-Jun protein, and its activated, phosphorylated form, peaking around 7 days after injury in preferentially large diameter CN-neurons ipsilateral and caudal to the lesion. Our results document that some populations of axotomized central nervous system neurons, similar to axotomized regenerating neurons of the peripheral nervous system, can up-regulate GAP-43 and C-Jun, even if they are destined to degenerate. This might reflect a transient regenerative capacity, which fails over time.

Animals↗
PubMed1999

[Neuroborreliosis with extensive cerebral vasculitis and multiple cerebral infarcts].

We report on a patient who suffered from borreliosis-induced severe cerebral vasculitis accompanied by multiple cerebral infarctions leading to hemiparesis, hemianopsia and reduced consciousness. Despite antibiotic and immunosuppressive therapy with ceftriaxon and prednisolone the patients condition deteriorated. Cerebral angiography showed multiple stenoses of large arteries of the posterior circulation and ubiquitous irregularities of small vessel wails. General reduced perfusion reflected an increased peripheral resistance. After 4 weeks of additional immunosuppressive treatment with cyclophosphamide the neurological status and angiographic findings improved dramatically.

Cerebral Angiography↗
PubMed1999

[Nerve regeneration after spinal cord trauma. Neurobiological progress and clinical expectations].

In recent years, a more precise neurobiological knowledge has been gained concerning the various cellular parameters which mediate successful peripheral nerve regeneration, and also those which prevent repair of damaged nerve fibre pathways following traumatic injury to the the central nervous system (CNS). On this basis, a range of experimental therapeutical approaches for promoting axonal regeneration and functional recovery after spinal cord injury have been developed in animal models. Such intervention strategies focus on the molecular inactivation of glial-associated growth-inhibitory factors and on the application of trophic molecules and cellular substrates which enhance the postlesional regenerative potential of intrinsic CNS neurons. At the present, these experimental therapies cannot be transferred to the clinical situation for the treatment of spinal cord injured patients. This overview briefly summarizes current progress in the neurobiology of spinal cord trauma, the main findings of which are discussed in the light of clinical expectations.

Animals↗
PubMed1998

Spontaneous orientation of transplanted olfactory glia influences axonal regeneration.

Transplanted olfactory ensheathing cells (OECs) have previously been demonstrated to support axonal growth and myelination in the adult rat CNS. Here, the capacity of donor OECs to control the direction of axonal regeneration has been investigated following transplantation, as elongated columns, into the thalamus of adult rats. The OECs formed a 'glial bridge' which extended from the thalamus to the hippocampus. Transplanted OECs rapidly adopted a spindle-shaped morphology which was orientated along the vertical axis of the transplant. Numerous host axons grew into the transplants and followed the highly orientated OEC cell matrix across the choroid fissure. Thus, the spontaneous elongation and orientation of donor OECs may support highly directional host axonal growth across natural barriers within the CNS.

Animals↗
PubMed1998

Spontaneous longitudinally orientated axonal regeneration is associated with the Schwann cell framework within the lesion site following spinal cord compression injury of the rat.

Spontaneous cellular reorganisation at the lesion site has been investigated following massive spinal cord compression injury in adult rats. By 2 days post operation (p.o.), haemorrhagic necrosis, widespread axonal degeneration, and infiltration by polymorphnuclear granulocytes and OX42-positive macrophages were observed in the lesion site. By 7 days p.o., low affinity nerve growth factor receptor-positive Schwann cells, from activated spinal roots, were identified as they migrated far into the lesion. Between 7 and 14 days p.o., the overlapping processes of Schwann cells within the macrophage-filled lesion formed a glial framework which was associated with extensive longitudinally orientated ingrowth by many neurofilament-positive axons. Relatively few of these axons were calcitonin gene-related peptide (CGRP)-, substance P (SP)-, or serotonin (5HT)-positive; however, many were glycinergic or gamma aminobutyric acid (GABA)ergic. At 21 and 28 days p.o. (the longest survival times studied), a reduced but still substantial amount of orientated Schwann cells and axons could be detected at distances of up to 5 mm within the lesion. Glial fibrillary acidic protein (GFAP) immunoreactivity demonstrated the slow formation of astrocytic scarring which only became apparent at the lesion interface between 21 and 28 days p.o. The current data suggest the possibility of developing future therapeutic strategies designed to maintain or even enhance these spontaneous and orientated regenerative events.

Animals↗
PubMed1998

A novel early component of the cell body response in axotomized Clarke's nucleus neurons revealed by monoclonal antibody Py.

The monoclonal antibody Py was initially developed as a tool for the identification of subpopulations of hippocampal neurons. Recently it has also been demonstrated to be a useful marker for other populations of midbrain and spinal cord neurons in which the antigen showed a strong colocalization with cytoskeletal elements. To assess the possible usefulness of Py as a tool for studying lesion-induced cell body changes, densitometric analysis of altered Py-immunoreactivity (Py-IR) has been compared with that of microtubule-associated protein 2 (MAP2) in Clarke's nucleus following axotomy. One week after a unilateral transection of the dorsal spinocerebellar tract at Th9-10, Py-IR in the Clarke's nucleus ipsilateral and caudal to the lesion was reduced by approximately 40%. By 21 days, Py-IR was reduced by approximately 50% (a near maximal reduction) and remained constant up to 5 months after the lesion (the longest survival time studied). Alterations of MAP2-IR in Clarke's nucleus were later in onset, slower to develop, and less marked. The differential distribution of the Py antigen in the CNS and its rapid and long lasting loss indicate that the Py antibody is a sensitive tool for studying novel early alterations of the cytoskeleton which may be important molecular events in axotomy-induced pathological processes.

Animals↗