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Results for “Diffuse Axonal Injury”

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PubMed1981

The temporo-spatial course of degeneration after cutting cortico-cortical connections in adult rats.

Adult albino rats received callosotomies or lesions in the paracingular cortex. Between 12 h and 3 months after injury the structure and topography of the degeneration products were studied by light- and electron-microscopy. The degeneration process was quantified by television-image analysis applied to sections prepared according to a new technique that stains reliably degenerating terminals and lysosomes (Gallyas et al. 1980). All types of cortico-cortical connections show a multiphasic degeneration process: During a precursor stage a small number of dense bodies and mitochondrial granules are stained. These and the few early degenerating axon terminals are much more diffusely distributed than the large number of terminals that degenerate during the following period. The terminal degeneration shows a biphasic time course. One maximum appears at 2-7 days post operation, which corresponds to the well known direct consequence of axotomy. The second peak at 10-20 days post operation could be caused by transneuronal reorganization of the cortical connectivity. Terminal degeneration always begins along the borders between cortical regions and areas, but it may change its laminar and columnar distribution pattern during the second phase. The degeneration products that are phagocytosed by astrocytes seem to be removed by intracellular transport to their perivascular endfeet. The degeneration process ends with fiber degeneration which, especially in laminae I and VI, may form a separate peak after 20 days or more.

Animals↗
PubMed1986

The role of growth factors in neuronal development and plasticity.

The role of growth factors in the development of the nervous system, as well as in injury-induced plasticity, is of great interest. A neuronal growth factor is any substance that influences the growth of neurons, but two general classes of factors exist: diffusible substances and substrate-bound factors. Growth factors may affect neuronal survival as well as the extent and rate of neurite outgrowth in vitro. Although progress is slowly being made in the identification and characterization of putative growth factors, nerve growth factor (NGF) is the only identified molecule that clearly influences neuronal growth in vivo. Furthermore, although there are many examples of neuronal plasticity following injury, the role of growth factors in such rearrangements remains to be established. However, one model of collateral sprouting of axons from the peripheral nervous system (PNS) into the central nervous system (CNS) appears to involve the action of a growth factor with properties similar to NGF. The identification of specific molecules that affect neuronal growth should lead to an understanding of the etiology of degenerative neurological diseases such as Alzheimer's disease and, hopefully, to rational therapeutic approaches.

Animals↗
PubMed2001

Electrical activity modulates growth cone guidance by diffusible factors.

Brief periods of electrical stimulation of cultured Xenopus spinal neurons resulted in a marked alteration in the turning responses of the growth cone induced by gradients of attractive or repulsive guidance cues. Netrin-1-induced attraction was enhanced, and the repulsion induced by myelin-associated glycoprotein (MAG) or myelin membrane fragments was converted to attraction. The effect required the presence of extracellular Ca(2+) during electrical stimulation and appeared to be mediated by an elevation of both cytoplasmic Ca(2+) and cAMP. Thus, electrical activity may influence the axonal path finding of developing neurons, and intermittent electrical stimulation may be effective in promoting nerve regeneration after injury.

Animals↗
PubMedDate not supplied

Schwann cell changes and demyelination in chronic galactose neuropathy.

Dystrophic changes of Schwann cells and demyelination occurred in rats with chronic nerve edema induced by feeding a galactose-rich diet for two years. The mechanism for edema is the sorbitol pathway which generates osmotically active polyols from galactose or glucose. The blood-nerve barrier impedes diffusion of macromolecules from peripheral nerves, and endoneurial fluid pressure (EFP) becomes elevated. After 24-26 months of feeding with 40% galactose diet, myelinated nerve fibers showed segmental demyelination with bubbly disintegration of myelin sheaths, axonal degeneration, and remyelination. These pathologic changes were significantly more common than similar abnormalities in age-matched controls. Massive glycogen accumulation in Schwann cells, a unique morphologic finding, appeared only in experimental rats. Since edema and increased EFP are the earliest pathologic changes and are present for months before demonstrable nerve fiber injury, we suggest that they are responsible for the changes of myelinated fibers in chronic galactose neuropathy.

Animals↗
PubMed1996

Calcitonin gene-related peptide level in the rat dentate gyrus increases after damage.

Calcitonin gene related peptide-like immunoreactivity (CGRP-LI) was examined in rat dentate gyrus (DG) following damage to granule cells by adrenalectomy or intrahippocampal colchicine injections. In normal DG, CGRP-LI was present in a diffuse hand within the inner third of the molecular layer (ITML) and in hilar cells. Following the experimental procedures, levels of CGRP-LI increased bilaterally in the ITML and in hilar interneurons resembling mossy cells. Ultrastructural analysis of the ITML revealed that CGRP-LI is associated with large, dense-core vesicles within axon terminals which form asymmetrical synapses with dendritic spines, and within dendritic spines. The increase in CGRP-LI level following granule cell damage suggests a protective role for CGRP in the response to hippocampal injury.

Adrenalectomy↗
PubMedDate not supplied

Gd-DTPA enhanced MR of the lumbar spinal canal in patients with claudication.

OBJECTIVE: The purpose of this work was to study the findings on intravenous gadolinium-enhanced MRI of the lumbar spinal canal in patients with clinically suspected neurogenic claudication. MATERIALS AND METHODS: A prospective gadolinium-enhanced MR evaluation of seven adult patients presenting with clinical claudication thought to be related to the lumbosacral spine was undertaken. RESULTS: Of seven consecutive enhanced conventional SE MRI examinations of the lumbosacral spine in patients presenting with lower extremity claudication, five patients (71.4%) revealed abnormal intrathecal enhancement on MR at and extending craniad from the level(s) of severe spinal stenosis. Each of the seven patients (100%) showed relatively severe central stenosis of the lumbar spinal canal. The enhancement pattern was linear, curvilinear, punctate, and/or diffuse in configuration. Two of the five patients with intrathecal enhancement also showed similar abnormal intrathecal enhancement extending caudal to the severely stenotic levels. CONCLUSION: The clinically significant intrathecal enhancement on intravenous gadolinium-enhanced MRI identified above the level of a severely stenotic lumbar spinal canal hypothetically might represent enhancement of dilated, obstructed venous structures serving the cauda equina. More likely, however, the major factor in such enhancement at, above, and/or below the stenosis signals blood-nerve barrier breakdown associated with mechanical injury, inflammatory response, and wallerian degeneration/regeneration of axons within chronically compressed nerve roots.

Adult↗
PubMed1982

The pathophysiology of compression injuries of the peripheral facial nerve.

The buccolabial branches of guniea pig facial nerves were crushed to produce axonotmesis, Wallerian degeneration, and demyelination. The lesions were followed from 1 to 8 weeks by transmission electron microscopy, electrophysiological tests, and cytochemical staining methods for Na+ channels. The first week demonstrated the classic degenerative neural changes. At 2 weeks the axoplasmic side of the demyelinated axolemma demonstrated diffuse staining for Na+ channels at a distance of 1 micrometer. At 4 weeks multiple condensed areas of dense staining were noted along the demyelinated axolemma. These staining areas resemble in character and length a normal node of Ranvier and denote new Na+ channels. The internodal distance is shorter than for the normal facial nerve. At 6 weeks a thin layer of myelin covered the nerve fibers. At 8 weeks half of the nerves were normal sized and the myelin sheath was normal in width. Following nerve crushing, electrical activity is present for 24-48 hours in the axonotmetic distal stump. Then the axon becomes unresponsive to electrical stimulation. There is gradual resumption of electrical activity between 5 and 14 days. Normal conduction resumes by 8 weeks. This study provides ultrastructural and cytochemical evidence for nerve fiber reorganization, axolemmal plasticity and sodium channel production and redistribution following Wallerian degeneration and demyelination in axonotmesis. Resumption of electrical neural excitability is achieved by an increase in the density of sodium channels and reduction in the internodal distance as a means for impedence matching. Reduction of the cross sectional diameter of the regenerating axon facilitates electrical conduction.

Animals↗
PubMed1999

Structural basis of sympathetic-sensory coupling in rat and human dorsal root ganglia following peripheral nerve injury.

Tyrosine hydroxylase immunocytochemistry was used to reveal the sympathetic postganglionic axons that sprout to form basket-like skeins around the somata of some primary sensory neurons in dorsal root ganglia (DRGs) following sciatic nerve injury. Ultrastructural observations in rats revealed that these sprouts grow on the surface of glial lamellae that form on the neurons. Sciatic nerve injury triggers glial cell proliferation in the DRG, and the formation of multilamellar pericellular onion bulb sheaths, primarily around large diameter DRG neurons. We infer that these glia participate in the sprouting process by releasing neurotrophins and expressing growth supportive cell surface molecules. Many DRG cell somata, and their axons in intact nerves and nerve end neuromas, express alpha2A adrenoreceptors intracytoplasmically and on their membrane surface. However, sympathetic axons never make direct contacts with the soma membrane. The functional coupling known to occur between sympathetic efferents and DRG neurons must therefore be mediated by the diffusion of neurotransmitter molecules in the extracellular space. Sympathetic basket-skeins were observed in DRGs removed from human neuropathic pain patients, but the possibility of a functional relation between these structures and sensory symptoms remains speculative.

Adult↗
PubMed1994

Regeneration of perineurium after nerve injury and autografting. An experimental study.

Regeneration of the perineurium after crush injury to the rat sciatic nerve and after autografting was studied in an experimental model. After injury, fibroblast-like cells formed compartments inside the funiculus which gradually acquired the characteristics of the perineurial cell. After grafting, the pattern of perineural regeneration depended on the degree of Schwann cell damage. In the graft and distal nerve trunk the epineurium degenerated and disappeared and new perineural tissue was formed by endoneurial fibroblasts from the inside of the funiculus. At the suture line, fibroblasts encircled the regenerating axons and the Schwann cells to form new compartments resulting in a large number of minifasciles of regenerating nerve. The function of the perineurium as a diffusion barrier was restored satisfactorily in the crushed nerve, although there was no satisfactory repair at 30 weeks after nerve grafting.

Animals↗
PubMed2004

[Delayed post-anoxic leukoencephalopathy].

INTRODUCTION: The onset of post-anoxic encephalopathies can be delayed after the acute hypoxic injury. CASE REPORT: We present the case of a 45-year-old woman who achieved complete recovery from an episode of hypoxia related to a suicide attempt (ingestion of benzodiazepine). Three weeks later she developed a confusional state with akinetic mutism and parkinsonism. Brain CT-scan showed bilateral hemispheric white matter hypodensities. MRI showed extensive bilateral hyperintensities on T2-weighted and Flair sequences within the hemispheric white matter and the globus pallidus. EEG showed diffuse slow activity. All investigations for leukodystrophies were negative. Brain biopsy showed normal cortex and widespread demyelination with axonal sparing in the underlying white matter. The patient experienced a partial clinical recovery. CONCLUSION: The clinical course and the results of paraclinic investigations were consistent with the diagnosis of delayed post-anoxic leukoencephalopathy.

Female↗
PubMed1993

Administration of 3,3'-iminodipropionitrile to the rat results in region-dependent damage to the central nervous system at levels above the brain stem.

Axonal swellings and neurofilamentous accumulations in the brain stem, spinal cord and peripheral nervous system are the most widely documented effects of exposure to 3,3'-iminodipropionitrile (IDPN). Evidence from morphological and functional studies, however, suggests that IDPN also may damage areas of the central nervous system above the level of the brain stem. To examine this possibility, we evaluated the astrocyte reaction to injury as an indirect means of detecting potential sites of IDPN-induced damage to the central nervous system. An immunoassay for the astrocyte intermediate filament protein, glial fibrillary acidic protein (GFAP), was used to quantify gliosis. Rats were given IDPN (0-600 mg/kg/day i.p.) for 3 days. The concentration of GFAP in discrete brain regions was examined at postdosing times ranging from 3 days to 3 weeks. IDPN caused time-, dose- and region-dependent increases in GFAP; elevations were observed in the pons-medulla, midbrain, cerebral cortex and olfactory bulbs, but not in cerebellum, hypothalamus, hippocampus and striatum. Of these areas, cortex and olfactory bulbs showed the largest increases. Dissection of cortex into four subregions showed that the IDPN-induced increase in cortical GFAP was relatively uniform across this brain region. Application of the de Olmos cupric-silver degeneration stain to IDPN-treated tissue revealed intense argyrophilia in the glomerular layer of the olfactory bulbs and diffuse staining of axons in several regions of the cortex. The data indicate that IDPN is neurotoxic to the olfactory bulbs and cortex of the rat.

Animals↗
PubMed2003

Morphological changes and stress responses in neurons in cerebral cortex infiltrated by diffuse astrocytoma.

Local dysfunction in cerebral cortex infiltrated by astrocytoma can cause epilepsy and focal neurological deficits, but the cellular pathology of peritumoral cortex remains poorly defined. The aims of the present study were to define the morphological changes which occur in neurons in tumor-infiltrated cerebral cortex, and to determine whether peritumoral neurons show expression of cell stress-related proteins. Archival specimens of diffuse astrocytoma (n = 28) were identified with areas of both tumor-infiltrated cortex and apparently non-infiltrated cortex. Immunohistochemistry was performed to structural neuronal proteins (MAP-2, neurofilament proteins), beta-amyloid precursor protein, growth associated protein-43 and to injury response proteins (poly(ADP-ribose) polymerase, poly(ADP-ribose), c-fos, and c-jun). Tumor-infiltrated cortex revealed neuronal loss and architectural disarray compared to non-infiltrated cortex. Pyramidal neurons showed thinning of the cytoplasmic rim and their neuritic processes showed increasing tortuosity, varicosity, fragmentation and loss, with axonal spheroid formation and dendritic beading. Poly(ADP-ribose) polymerase, poly(ADP-ribose) and c-fos were up-regulated in both infiltrated and non-infiltrated cortex, but c-jun expression was greater in areas of tumor-infiltrated cortex. Surviving neurons in cortex infiltrated by astrocytoma demonstrate, therefore, a sequence of morphological alterations in their dendritic, somatic and axonal compartments, and demonstrate a cell stress response. The patterns of cellular pathology identified suggest possible mechanisms, by which neurons are damaged and eventually lost in peritumoral brain.

Astrocytoma↗
PubMed1991

[A clinico-neurophysiological analysis and the treatment problems of the crush syndrome (based on data from the earthquake in Armenia)].

Overall 350 patients with the crush syndrome were examined. It has been shown by the clinico-neurological investigation that in long compression of the limbs followed by the development of the crush syndrome, sensitive fibers and the membrane of the axon are most of all exposed to unfavourable effects. The changes discovered as a result of the clinically intact nerves point to the diffuse impairment of the peripheral neuromotor apparatus in patients with the crush syndrome.

Armenia↗
PubMed1993

Distinct neuronal subset reveals perikaryal immunostaining for synaptophysin (protein p38) in the striatum of rats.

An immunoperoxidase technique was used to locate synaptophysin (protein p38), a major integral membrane glycoprotein of synaptic vesicles, in the rat brain. In addition to a diffuse distribution of nerve terminal stainings for synaptophysin appearing as numerous small puncta, the large-sized cells with spindled or polygonal shapes revealed perikaryal staining for synaptophysin in the striatum. The double labeling with immunofluorescence technique disclosed that the cell bodies, immunoreactive for synaptophysin, appeared to be those of the striatal giant cholinergic neurons. In addition, in rats that underwent the transient middle cerebral artery occlusion, the striatal ischemic lesions with cell type-specific injury revealed a survival of synaptophysin-positive large cells, presumably identical with the cholinergic neurons. The present study suggests that the metabolism and/or axonal transportation of synaptophysin of the giant cholinergic cells may be different from those of other neuronal populations in the striatum. Also, synaptophysin can act as a neurochemical marker for identification of the giant cholinergic neurons in the striatum of rats.

Animals↗
PubMed1978

Lysosomal activity in experimental spinal cord trauma: an ultrastructural cytochemical evaluation.

The possible role of lysosomal activity in the early post-trauma phase of severe experimental spinal cord trauma was assessed utilizing an acid phosphatase cytochemical ultrastructural study. The results indicate that there is no evidence for lysosomal alteration prior to the development of cellular degeneration or necrosis. No diffuse cytoplasmic staining was observed. This study indicates that physical lysosomal injury resulting in release of hydrolases into spinal cord cells is not a tenable hypothesis as a primary initiating event in the development of spinal cord necrosis following trauma. However, the data are consistent with the general theory that lysosomal activity is important in the secondary degradation of cells following their being altered beyond recovery.

Acid Phosphatase↗
PubMed1995

Directional regrowth of lesioned corticospinal tract axons in adult rat spinal cord.

During central nervous system development, gradients of diffusible molecules play an important role in the attraction of outgrowing axons. A diffusible tropic factor released by the cervical spinal gray matter attracts outgrowing corticospinal tract axons, as shown by in vitro collagen co-culture studies [Joosten E. A. J. et al. (1994) Neuroscience 59, 33-41]. Here we study the effects of local application of timed cervical spinal gray matter extracts on regrowth of injured corticospinal tract axons in the adult rat spinal cord. For local application of target-derived extracts at the site of lesion we used rat tail collagen type 1 as a matrix. Ingrowth of anterogradely labelled corticospinal tract axons into the collagen was studied four weeks after the spinal cord injury. No ingrowth of labelled corticospinal tract axons can be observed in the control experiment when collagen only was applied into the lesion gap. Furthermore, we found that local application of an extract derived from four-day, but not from one-day or 16-day-old, cervical spinal cord gray matter directs a substantial amount of the lesioned adult corticospinal tract axons into the collagen implant. We conclude that directional regrowth of injured corticospinal tract axons in the adult rat spinal cord is possible by local application of timed target-derived extracts. In this respect spatiotemporal aspects are of the utmost importance.

Animals↗
PubMed1976

Incorporation of tritiated leucine by axotomized rubral neurons.

Fourteen kittens, 7--10 weeks of age, were injected with [3H]leucine 0.5--24 h before sacrifice 1--30 days after unilateral high cervical rubrospinal tractotomy. Histoautoradiographs of the red nuclei were prepared and counterstained with thionin. Axon reaction, evident histologically 24 h after surgery, was manifested by central chromatolysis or diffuse cytoplasmic chromophobia. Partial reversion toward a normal cytologic appearance was apparent 10--30 days postoperatively. Nucleolar and nuclear shrinkage and cytoplasmic atrophy were conspicuous accompaniments of axon reaction in rubral neurons. Expressed per cell the radioactivity of axotomized rubral nerve cells was consistently less than controls in animals surviving operation from 5 to 30 days. The data indicate that axon reaction in red nucleus is regressive in character and early associated with diminished protein synthesis. The frequently regressive nature of axon reaction in intrinsic neurons, such as those of red nucleus, probably is important in accounting for failure of regeneration of many mammalian CNS fiber tracts after injury.

Animals↗
PubMed2003

Molecular mechanisms of axonal damage in inflammatory central nervous system diseases.

PURPOSE OF REVIEW: Axonal dysfunction and damage is an early pathological sign of autoimmune central nervous system disease, viral and bacterial infections, and brain trauma. Axonal injury has attracted considerable interest during the past few years because the degree of axonal damage appears to determine long-term clinical outcome. RECENT FINDINGS: Advanced magnetic resonance spectroscopic imaging techniques have suggested that axonal loss and dysfunction is responsible for the persistent neurological deficits that occur in patients with multiple sclerosis. Histopathological methods have shown that axonal damage is defined primarily by dysfunction of axonal transport, and finally by complete transection and degeneration of axons. Recent studies have demonstrated that the extent of axonal damage in the primary demyelinating lesion of multiple sclerosis patients is associated with the number of activated microglia/macrophages and cytotoxic CD8+ T lymphocytes. In addition, diffuse axonal dysfunction independent of demyelination develops in normal appearing white matter, possibly due to indirect effects of inflammation. SUMMARY: The fact that axonal damage in response to overt inflammatory reactions may occur gradually, leaving a window for therapeutical intervention, has important clinical implications. Determination of the exact molecular mechanism might help in finding new therapies for inflammatory axonal damage.

Animals↗